阅读说明：本技术 一种抗肿瘤组合物、治疗癌症的药物制剂及其应用 (Anti-tumor composition, pharmaceutical preparation for treating cancer and application of pharmaceutical preparation ) 是由 钱碧云 张奇 朱滕滕 冯铁男 杨雨晴 钱颖 谢丽 于 2019-11-26 设计创作，主要内容包括：本发明涉及一种抗肿瘤组合物、治疗癌症的药物制剂及其应用,所述抗肿瘤组合物包括含有治疗有效量的d-柠檬烯,以及用于增强d-柠檬烯治疗效果的月桂烯、芳樟醇、癸醛和3-蒈烯。与现有技术相比,本发明的抗肿瘤组合物以及对应药物制剂对肿瘤细胞(特别是肺癌细胞)具有明显的增殖抑制活性,并抑制细胞的迁移与侵袭,影响癌细胞相关蛋白与基因水平的表达从而促进肿瘤细胞凋亡等。(The invention relates to an anti-tumor composition, a pharmaceutical preparation for treating cancer and application thereof, wherein the anti-tumor composition comprises d-limonene with a therapeutically effective amount, and myrcene, linalool, decanal and 3-carene for enhancing the treatment effect of the d-limonene. Compared with the prior art, the anti-tumor composition and the corresponding pharmaceutical preparation have obvious proliferation inhibition activity on tumor cells (particularly lung cancer cells), inhibit migration and invasion of the cells, and influence expression of cancer cell-related proteins and gene levels so as to promote apoptosis of the tumor cells and the like.)

1. An anti-tumor composition comprising a therapeutically effective amount of d-limonene, myrcene, linalool, decanal, and 3-carene for enhancing the therapeutic effect of d-limonene.

2. The anti-neoplastic composition of claim 1, wherein the volume ratio of d-limonene, myrcene, linalool, decanal, and 3-carene is (80-99): (1-5): (1-5): (1-5): (1-5).

3. The anti-neoplastic composition of claim 2, wherein the volume ratio of d-limonene, myrcene, linalool, decanal, and 3-carene is 96: 1: 1: 1: 1.

4. a pharmaceutical formulation for the treatment of cancer comprising a therapeutically effective amount of an anti-neoplastic composition according to any one of claims 1 to 3 and a pharmaceutically acceptable pharmaceutical excipient.

5. The pharmaceutical preparation for treating cancer according to claim 4, wherein the dosage form is oral preparation or parenteral preparation.

6. The pharmaceutical formulation for treating cancer according to claim 5, wherein the oral formulation is any one of tablet, pill, capsule, granule, microcapsule tablet, suspension, dripping pill or oral liquid formulation.

7. The pharmaceutical preparation for treating cancer according to claim 5, wherein the parenteral dosage form is any one of injection, aerosol, suppository or subcutaneous dosage form.

8. Use of an anti-tumor composition according to any one of claims 1 to 3 for the preparation of a medicament for the treatment of cancer.

9. The use of the anti-neoplastic composition of claim 8, wherein the cancer is lung cancer.

10. Use of a pharmaceutical formulation according to claim 4 in the manufacture of a medicament for the treatment of cancer.

Technical Field

The invention belongs to the technical field of antitumor drugs, and relates to an antitumor composition, a pharmaceutical preparation for treating cancer and application thereof.

Background

Cancer is one of the major diseases threatening human health and life. Malignant tumors grow rapidly in an invasive manner, are prone to bleeding, necrosis and ulcer, often accompany with distant metastasis, cause emaciation, weakness, anemia, inappetence, fever and serious organ function impairment, and finally cause death of patients. The cancer forms are severe in China, and the morbidity and the mortality of China are in a continuously rising trend. At present, the search for high-efficiency and low-toxicity antitumor drugs from plants has become the key point of research on antitumor drugs at home and abroad.

Limonene (D-limonene), also known as limonene, 1-methyl-4- (1-methylethenyl) cyclohexene, p-limonene

-1, 8-diene, cajeput terpene, present in lemongrass oil, pine needle oil, vanilla oil, turpentine, having a fresh orange aroma and a lemon-like aroma. Has good effects of relieving cough, eliminating phlegm and inhibiting bacteria, and the compound limonene can be clinically used for cholagogue, dissolving stone, promoting secretion of digestive juice and eliminating intestinal pneumatosis. Myrcene (Myrcene), also known as Myrcene, a Myrcene is less naturally present and B Myrcene is often used in the fragrance industry. B, myrcene is colorless or light yellow liquid and has light balsam fragrance. Insoluble in water and soluble in organic solvent such as ethanol. Is present in oleum Cinnamomi, lemongrass oil, cedar wood oil, spruce oil, oleum Terebinthinae, lemongrass oil, lemon oil, etc.

Linalool (Linalool) with molecular formula C₁₀H₁₈O, is chain terpene alcohols, has α -and β -isomers, is colorless liquid, and has antibacterial and tranquilizing effectsAnd the like.

Decanal (decanol) is also called decacarbaldehyde and n-Decanal. Is commonly used for organic synthesis and blending of edible flavor, and is found in citrus, lemon, tomato, strawberry.

The 3-carene (3-carene) is the main component of monoterpene in the essential oil, has strong pine-like fragrance, can be applied to various edible essences, and can also be used as a raw material for synthesizing spices.

Many documents describe that d-limonene is used alone or in combination with other synergistic components for treating cancer, for example, chinese patent CN106890140A discloses a d-limonene anticancer synergistic composition and a preparation method thereof, wherein the d-limonene anticancer synergistic composition comprises 0.5-10% of d-limonene, 0.1-5% of chitosan oligosaccharide, and 0.5-10% of plant-derived surfactant. However, no report is available for preparing a pharmaceutical dosage form by using a mixture of d-limonene, myrcene, linalool, decanal and 3-carene as raw materials and treating tumor diseases.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide an anti-tumor composition, a pharmaceutical preparation for treating cancer and application thereof, which are represented as follows: has obvious proliferation inhibiting activity on lung cancer cells, inhibits migration and invasion of the cells, and influences the expression of lung cancer cell-related proteins and gene levels so as to promote tumor cell apoptosis. Therefore, the composition can be used for development and application of anti-lung cancer clinical drugs or tumor chemoprevention drugs.

The purpose of the invention can be realized by the following technical scheme:

one technical scheme of the invention is to provide an anti-tumor composition, which comprises d-limonene with a therapeutically effective amount, and myrcene, linalool, decanal and 3-carene for enhancing the treatment effect of the d-limonene.

Further, the volume ratio of the d-limonene, the myrcene, the linalool, the decanal and the 3-carene is (80-99): (1-5): (1-5): (1-5): (1-5).

Furthermore, the volume ratio of the d-limonene, the myrcene, the linalool, the decanal and the 3-carene is 96: 1: 1: 1: 1.

the second technical scheme of the invention provides a pharmaceutical preparation for treating cancer, which comprises a therapeutically effective amount of the anti-tumor composition and pharmaceutically acceptable pharmaceutical excipients.

Further, the pharmaceutical excipient may include diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorption carriers or lubricants, etc., which are conventional in the pharmaceutical field, so as to prepare the anti-tumor composition into various formulations.

Further, the dosage form is an oral preparation or a parenteral preparation.

Furthermore, the oral preparation is any one of tablets, pills, capsules, granules, microcapsule tablets, suspensions, dropping pills or oral liquid preparations.

Further, the parenteral administration preparation is any one of injection, aerosol, suppository or subcutaneous administration dosage form.

The third technical scheme of the invention is to provide the application of the anti-tumor composition in preparing a medicament for treating cancer.

Further, the cancer is lung cancer.

The fourth technical scheme of the invention is to provide the application of the pharmaceutical preparation in preparing the medicine for treating cancer. Further, the cancer is preferably lung cancer.

In the technical scheme of the invention, the anti-tumor composition can also contain other anti-tumor drugs, such as cisplatin and/or rapamycin, besides d-limonene, myrcene, linalool, decanal and 3-carene. Or adding flavone or alkaloid with anti-tumor activity.

Drawings

FIG. 1 is a graph of the in vitro proliferation inhibitory effect of limonene and compositions on tumor cells A549;

FIG. 2 is a graph of the in vitro proliferation inhibitory effect of limonene and compositions on tumor cells H1975;

FIG. 3 shows the invasion inhibiting effect of limonene and the composition on tumor cells A549 and H1975;

FIG. 4 shows the results of inhibition of tumor cell A549 invasion by limonene and the composition;

FIG. 5 shows the results of inhibition of invasion of tumor cells A549 by limonene and the composition;

FIG. 6 shows the migration inhibitory effect of limonene and compositions on tumor cells A549, H1975;

FIG. 7 shows the migration inhibition of tumor cells A549 by limonene and the composition;

FIG. 8 shows the results of the migration inhibition of tumor cells A549 by limonene and the composition;

FIG. 9 shows the cell clone inhibition of tumor cells A549 and H1975 by limonene and compositions;

FIG. 10 shows the results of cell clone inhibition of tumor cells A549 by limonene and the composition;

FIG. 11 shows the results of cell clone inhibition of tumor cells A549 by limonene and the composition;

FIG. 12 is a graph of the pro-apoptotic effect of limonene and compositions on tumor cells A549, H1975;

FIG. 13 is a graph of the pro-apoptotic results of limonene and compositions on tumor cells H1975;

figure 14 is a graph of the pro-apoptotic results of limonene and compositions on tumor cells a 549.

Detailed Description

The invention is described in detail below with reference to the figures and specific embodiments. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.

In the following examples: the A549 and H1975 cell purchasing is performed at 37 deg.C and 5% CO with the Collection of Shanghai Life science research institute of Chinese academy of sciences₂Culturing in an incubator.

Preparation of main solution (all solution preparation water is ultrapure water):

(1) cell culture medium (complete medium): DMEM medium (high-glucose serum-free) + 10% FBS (fetal bovine serum) + 1% PIS (diabody), i.e. 89: 10: 1; sealing with sealing film, and storing at 4 deg.C.

(2) Phosphate Buffered Saline (PBS): KH (Perkin Elmer)₂PO₄0.20g、Na₂HPO₄.12H₂3.56g of O, 8.00g of NaCl and 0.20g of KCl, adding ultrapure water to 1000ml, adjusting the pH value to 7.2-7.4, and sterilizing at high pressure and storing at 4 ℃.

(3) An anti-tumor composition: mixing d-limonene, myrcene, linalool, decanal and 3-carene in a certain proportion, dissolving in DMSO, sealing with sealing film, and storing at 4 deg.C.

And the rest raw materials, processes, apparatuses, operation methods and the like which are not specifically described are all conventional commercial raw materials or conventional techniques in the field.