CN107260734B - Compound pharmaceutical composition with anti-lung cancer effect and application thereof - Google Patents
Compound pharmaceutical composition with anti-lung cancer effect and application thereof Download PDFInfo
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- CN107260734B CN107260734B CN201710523641.9A CN201710523641A CN107260734B CN 107260734 B CN107260734 B CN 107260734B CN 201710523641 A CN201710523641 A CN 201710523641A CN 107260734 B CN107260734 B CN 107260734B
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- lung cancer
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- piperlongumine
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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
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
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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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
Abstract
The invention belongs to the field of natural medicines, and discloses a compound medicine composition with an anti-lung cancer effect and application thereof. The active ingredients of the compound pharmaceutical composition consist of piperlongumine and emodin in a molar ratio of 1:1-1: 10. The two combined medicines have stronger synergistic application in treating lung cancer.
Description
Technical Field
The invention belongs to the field of natural medicines, and particularly relates to a compound medicine composition containing piperlongumine and emodin and having an anti-lung cancer effect and application thereof.
Background
Lung cancer is one of the most rapidly growing malignancies that threaten human health and life. In many countries, the incidence and mortality of lung cancer have been reported to be significantly higher in recent 50 years, with lung cancer incidence and mortality in men accounting for the first of all malignancies, in women accounting for the second, and mortality accounting for the second. The etiology of lung cancer is not completely clear. Currently, common treatment modalities for treating lung cancer are: surgery, radiotherapy, chemotherapy and traditional Chinese medicine treatment. Among them, surgery and radiotherapy are the most commonly used methods, but the risk of surgical treatment is high, the cost is high, and the side effect of radiotherapy is large, thereby greatly increasing the pain of lung cancer patients. In recent years, some drugs for treating lung cancer have gradually appeared on the market, for example: platinum group, and tinib group. However, the overall therapeutic effect of the above drugs is still not optimistic and the drugs are easy to recur. Therefore, the research and development of a lung cancer with good treatment effect and difficult recurrence is a difficult problem to be solved at present. Therefore, the method has important significance for searching safe, effective and low-toxicity antitumor drugs and researching the action mechanism of the antitumor drugs.
Piperlongumine (P L M), also called piperlongumine (Piperadiline), belongs to alkaloid compounds, which are originally separated from roots of Piper longum L in, Piper longum, Piper turbergatum, Jacq, and the like, of Piper longum, and the like, are studied deeply, and the Piperlongumine is found to have various pharmacological effects, wherein the Piperlongumine has a remarkable cytotoxic effect on tumor cells, can regulate the blood lipid metabolism of hyperlipidemic rats, and shows various pharmacological activities of resisting platelet aggregation, easing pain, resisting fungi and the like.
Emodin (ED) is one of the main active ingredients of rhubarb, has the functions of diminishing inflammation, inhibiting bacteria, resisting viruses and the like, and in recent years, researches find that Emodin (ED) has obvious broad-spectrum anti-tumor effect, lower toxic and side effects and stronger selectivity, thus being of great concern. The research of the emodin anti-tumor effect mainly aims at 4 aspects of inhibiting tumor growth, inhibiting migration invasion, enhancing curative effect by combined medication and sensitizing and attenuating by adjuvant chemotherapy. ED has positive prevention and treatment effects on various cancers such as liver cancer, lung cancer, breast cancer, colorectal cancer and the like (Oncotarget.2017.doi: 10.18632/oncotarget.16611.; BiomedPharmacother.2017; 90: 222-. The ED anticancer mechanism mainly relates to the elimination of hydroxyl free radicals, has a selective killing effect on tumor cells, and can also inhibit the growth, apoptosis and differentiation of tumors by changing the molecular sequence of cell nucleic acid.
Based on the background, through literature research, the prevention and treatment effects of the combination of P L M and ED on malignant lung cancer are hardly reported in related literatures.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention mainly aims to provide a compound pharmaceutical composition with the effect of resisting lung cancer; the active ingredients of the compound pharmaceutical composition consist of piperlongumine and emodin.
The invention also aims to provide the application of the compound medicine composition with the anti-lung cancer effect; pharmacological tests prove that the compound medicine composition has a synergistic effect of resisting lung cancer.
The purpose of the invention is realized by the following technical scheme:
a compound medicinal composition with anti-lung cancer effect comprises piperlongumine and emodin as active ingredients.
Preferably, the molar ratio of the piperlongumine to the emodin is 1:1-1: 10.
More preferably, the molar ratio of the piperlongumine to the emodin is 1:1-1: 5.
The compound pharmaceutical composition also contains a pharmaceutically acceptable carrier.
The compound medicine composition with the lung cancer resisting effect is used for preparing the lung cancer resisting medicine.
The anti-lung cancer drug can be used for treating lung cancer of mammals including human.
Compared with the prior art, the invention has the following outstanding advantages and beneficial effects:
the inventor finds that the piperlongumine (P L M) and the Emodin (ED) are subjected to combined administration, particularly, the piperlongumine and the emodin have good synergistic effect on anticancer cells when the piperlongumine and the emodin are combined in a molar ratio of 1:1-1: 10.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
Example 1 screening and optimizing a piperlongumine (P L M) and Emodin (ED) compound pharmaceutical composition for lung cancer cells.
Taking the lung cancer cells in logarithmic growth phase, inoculating 3 × 10 cells respectively4Arranging the tumor cells on a 96-well plate, centrifuging and removing supernatant after 6 hours of growth, then performing administration according to the following groups, namely arranging no-drug adding group and drug adding group on the tumor cells, wherein the drug adding group is provided with ED and P L M single-drug group, ED and P L M combined drug using different molar ratio groups, each group is provided with 4-6 multiple holes, culturing for 24 hours, removing supernatant, adding 100 mu l of MTT (tetrazolium salt) serum-free culture solution containing 0.5mg/ml for culturing for 4 hours, adding 100 mu l of DMSO (dimethyl sulfoxide), placing on a micro-oscillator for oscillation for 10min, then placing on an enzyme labeling instrument for detecting OD value at 570nm, and calculating the inhibition rate of the growth of the tumor cells under each condition according to the following inhibition rate formula, wherein the specific result is shown in Table 1.
Inhibition rate (1-addition drug OD value/control group OD value)
Table 1 shows the IC at various concentrations of ED and P L M alone and in combination on cells 24 hours after administration50The inhibition rate.
When the molar ratio is changed, the concentration of the P L M and ED is adjusted to increase, and the inhibition rate is concentration-dependent.
TABLE 1 ED and P L M Single drug/combination 24 hours IC50(μM)
Example 2 Effect analysis of combination of P L M and ED
Based on the Median-effect Principle (middle effect Principle or Chou-Talalay combined index method), Combidrug statistical software is used for drawing a dose-effect curve and a combination index curve (fa-C curve) under different effects, and the synergistic, antagonistic or additive relationship between the two medicines is quantitatively evaluated from the relationship between the effect of the combination of the two medicines and the combination index. The method comprises the following specific steps:
the drug effect, i.e. inhibition ratio (fa) ═ 1- (mean OD570 value of test group/mean OD570 of tumor cell blank control group) according to the equation of medium effect fa/fu ═ D/DmmTaking log fa/fu which is mlogD-mlogDm, setting a which is mlogDm, b which is M, X which is logD, y which is logfa/fu, substituting the formula of middle effect to obtain y which is bx-a, wherein fa is the effect of the drug, fu which is 1-fa, D is the concentration of the drug, M is the slope, and Dm is the concentration of the middle effect, namely the concentration of the drug at 50% effect, calculating the concentration of the middle effect Dm (logDm) 865 (logDm-a/M) when two anticancer drugs are used singly and used together, calculating the concentration of the drug needed at various effects when the two drugs are used singly and used together [ D which is dDm (fa/f u)1/M ], calculating the combined use index of the two drugs when the two drugs are used together [ CI which is dD 1+ DX 24/DX 25 + DX 1/M ] 637 when the two drugs are used together and the concentration of the two drugs is not used as DX 42, and the two drugs are used together and the same as DX 3, and the two drugs used together and the two drugs can generate the effect of different mechanisms of No. DX 3, and No. DX 3 and No. DX can be used alone or No. DX 3<1, the combined effect of the two medicines is synergistic; CI is 1, the combined effects of the two medicines are added; CI>1, the combination of the two medicines has antagonistic effect.
Software analysis shows that the compound pharmaceutical composition has good synergistic effect, the specific effect is shown in table 2, according to the Principle of evaluation effect of media-effect principles, namely Strong synergistic effect (Very string synergy) when the CI index is less than 0.1, Strong synergistic effect (string synergy) when the CI index is 0.1-0.3, weak synergistic effect (Slight synergy) when the CI index is 0.3-0.7, near additive effect (near additive effect) when the CI index is 0.7-0.85, antagonistic effect when the CI index is more than 1.10 and more than 0.85-0.90, ED synergistic effect and P L synergistic effect, especially Strong synergistic effect when the two are compatible with each other, and good synergistic effect when the CI index is 1-1.10, and good synergistic effect when the CI index is 1-1.5.
TABLE 2 CI comparison of the combination index of different combinations of P L M and ED for 24 hours of A549 action
Example 3 Piperlongumine (P L M) and Emodin (ED) compound pharmaceutical composition is made into tablets according to the following prescription:
the prescription is as follows:
the preparation process comprises the following steps:
sieving the medicines and the auxiliary materials with a 80-mesh sieve respectively, fully mixing the piperlongumine with 50 g of microcrystalline cellulose and 12 g of sodium carboxymethyl starch, preparing a soft material by 10% starch slurry, granulating with a 18-mesh sieve, and drying at 60 ℃ to obtain granules 1. Emodin is fully mixed with 12 g of microcrystalline cellulose, 15 g of starch and 8 g of sodium carboxymethyl starch, 10% starch slurry is made into a soft material, the soft material is granulated by a 18-mesh sieve, and the soft material is dried at 60 ℃ to obtain granules 2. And (3) fully mixing the granules 1 and 2 according to an equivalent increasing principle, finishing granules by a 16-mesh sieve, adding magnesium stearate, uniformly mixing, and tabletting to obtain 500mg tablets.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (4)
1. A compound pharmaceutical composition with anti-lung cancer effect is characterized in that: the active ingredients of the compound pharmaceutical composition consist of piperlongumine and emodin; the molar ratio of the piperlongumine to the emodin is 1:1-1: 10.
2. The compound pharmaceutical composition with the effect of resisting lung cancer according to claim 1, which is characterized in that: the molar ratio of the piperlongumine to the emodin is 1:1-1: 5.
3. The compound pharmaceutical composition with the effect of resisting lung cancer according to claim 1, which is characterized in that: the compound pharmaceutical composition also contains a pharmaceutically acceptable carrier.
4. Use of the compound pharmaceutical composition with the anti-lung cancer effect according to any one of claims 1 to 3 in preparation of anti-stranguria lung cancer drugs.
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| CN109516926B (en) * | 2018-07-27 | 2021-09-17 | 四川大学 | Preparation and application of piperlonguminine derivative |
| CN109602744A (en) * | 2018-12-13 | 2019-04-12 | 中国人民解放军总医院 | Piperlongumine is preparing the application in antibacterial-anti-inflammatory drug |
| CN109620836B (en) * | 2018-12-24 | 2021-05-18 | 陕西科技大学 | Compound pharmaceutical composition with breast cancer resistance, application thereof and medicine based on composition |
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Non-Patent Citations (2)
| Title |
|---|
| "Piperlongumine inhibits lung tumor growth via inhibition of nuclear factor kappa B signaling pathway";Jie Zheng等;《Scientific Reports》;19960520;第571-576页 * |
| "Sensitization of HER-2/neu-overexpressing non-small cell lung cancer cells to chemotherapeutic drugs by tyrosine kinase inhibitor emodin";Lisha Zhang等;《 Oncogene》;19961231;摘要 * |
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