WO2014044028A1

WO2014044028A1 - Anti lung cancer drug made of oleum cassiae and major constituent cinnamaldehyde thereof and use thereof

Info

Publication number: WO2014044028A1
Application number: PCT/CN2013/071888
Authority: WO
Inventors: 王四旺; 张云龙; 谢艳华
Original assignee: 中国人民解放军第四军医大学
Priority date: 2012-09-18
Filing date: 2013-02-26
Publication date: 2014-03-27
Also published as: CN102988486A; KR20150030725A

Abstract

Disclosed are the use of oleum cassiae and major constituent cinnamaldehyde thereof in preparing anti lung cancer drugs and anti lung cancer drugs made of oleum cassiae and/or cinnamylaldehyde. It has been confirmed by research that methods such as MTT that oleum cassiae and its major constituent cinnamylaldehyde have a significantly inhibiting effect on the non-small-cell lung cancer cell A549 while cinnamic acid as the metabolic end product of cinnamylaldehyde does not have or only has a very weak inhibiting effect on A549. Oleum cassiae and its major constituent cinnamylaldehyde can be used for preparing anti lung cancer drugs.

Description

Anti-lung cancer drug made by cinnamon oil and its main component cinnamaldehyde and its application

The invention belongs to the technical field of medicine, and in particular relates to the application of cinnamon oil and its main component cinnamaldehyde in the preparation of a medicament for preventing lung cancer. Background technique

Cinnamon is the dry bark of Cinnamomum cassia Presl. Cinnamon oil, also known as cinnamon oil, is the volatile oil of dried cinnamon and leaves of cinnamon. It is a clear liquid with yellow or brownish yellow color. It has a specific aroma of cinnamon, sweet taste, relative density of 1.055-1.070, refractive index of 1.602- 1.614. Cinnamon oil was confirmed by GC-MS analysis. The chemical constituents were mainly cinnamaldehyde, cinnamic acetate, salicylaldehyde and cinnamic acid. The relative content of cinnamaldehyde was over 87%. Cinnamon oil has strong volatility. In case of light and heat instability, it has a significant effect on the pharmacological effects of volatile oil. Cinnamaldehyde, also known as cinnamaldehyde, phenyl acrolein, etc., has a chemical name of 3-phenyl-2-propenal, English name Cinnamic aldehyde; it has a strong cinnamon aroma and lasts. Cinnamaldehyde is insoluble in water, glycerin and petroleum ether, soluble in ethanol and ether, and can volatilize with water vapor; unstable in strong acid or strong alkaline medium, easy to cause discoloration, easy to oxidize in air; cinnamaldehyde The oxidation reaction occurs in the body and is converted into cinnamic acid (also known as cinnamic acid).

Studies have found that cinnamic acid has antibacterial [Li Xiaofang et al. Synthesis, antibacterial activity and cytostatic effect of cinnamic acid-8-hydroxyquinoline rare earth complex. Natural Product Research and Development, 2012; 24 ( 2 ) : 160- 163], anti-cancer [Lü Junming et al. Synergistic effect of cinnamic acid combined with Ndfipl on proliferation and apoptosis of human hepatoma cell line SMMC-7721. Journal of Clinical Medicine and Pharmacy, 2011; 15 ( 2 ): 27-30; Zhang Kezhen et al. Acid-induced apoptosis of NB cells. Journal of Wuhan University-Medical Science, 2003, 24 (4): 327; Zhu Wenyuan et al. Cellular differentiation of HL-60 by cinnamic acid combined with vitamin C. Cancer Research, 2003, 30 ( 2 ): 92] Inhibition of melanoma and hepatocarcinoma cell proliferation and differentiation in vitro (Huang Wei et al. Studies on the differentiation of BEL-7402 human hepatoma cells induced by cinnamic acid. Journal of Practical Cancer, 2000, 15: 12), It can bind to DNA to regulate the expression of certain genes, block the growth and proliferation of tumor cells and have no embryotoxicity [zhang QH, ShengH P, LohTT. Bcl-2 protects HL-60 cells from apoptosis by stabilixzing their intracelular calciun pools Life Sci, 2001, 68 ( 2 ): 873]; It is also reported that cinnamic acid can be used to treat tuberculosis [Li Wenlan et al. Comparative study of pharmacokinetics of cinnamic acid from different sources, Chinese Journal of Traditional Chinese Medicine, 2008; 33 ( 10 ): 1192-1195] and so on. Cinnamonic acid is widely used in medicine, food additives, cosmetics, agrochemicals, etc. [Liu Jingtao et al. Synthesis of cinnamic acid derivatives. Seeking medical advice (second half monthly), 2012; 10 (1): 351- 352].

Cinnamon oil and its main component cinnamaldehyde have various physiological activities and medicinal values. Easy to wake up, etc. [Determination of cinnamaldehyde content in cinnamon oil microemulsion by high performance liquid chromatography. Shizhen Guo Guoguo, 2011 ; 22 ( 6 ): 1325-1326] Report: "Cinnamon oil is widely used in medicine, food and lightening. Industrial research shows that cinnamon has antibacterial, anti-tumor, anti-ulcer, hypoglycemic, antithrombotic, antipyretic, analgesic, antispasmodic, aphrodisiac, insecticidal, antioxidant and other effects. Cinnamaldehyde is the main oil of cinnamon oil The active substance, cinnamon oil, has a high content of cinnamaldehyde, about 80-95%. Cinnamaldehyde is very unstable in the blood, and it is rapidly oxidized into cinnamic acid with low pharmacological activity after oral or intravenous administration into the blood. Irreversible transformation."

Previous studies have confirmed that cinnamon oil and its main component cinnamaldehyde have antithrombotic effects [Huang Jingqun et al. Characteristics of cinnamic aldehyde against platelet aggregation and thrombosis. China Clinical Rehabilitation; 2006; 10

(31): 34-36] and anti-tumor [Huang Jingqun et al. Effect of cinnamaldehyde on growth and apoptosis of human gastric cancer cell xenografts in nude mice. Acta Pharmacological Journal, 2006; 22 (5): 343-346] Anti-coxsackie virus was first discovered for the treatment of viral myocarditis [Ding Yuanyuan et al. Effect of cinnamaldehyde on viral colic myocarditis induced by mouse coxsackie virus. Natural Product Research and Development, 2010; 22 ( 5 ): 769-776; Yuanyuan Ding , ed al. Influence of Cinnamaldehyde on Viral Myocarditis in Mice. Am J Med Sci. 2010; 340

(2): 114-20] and other pharmacological effects, the Chinese invention patent was filed in 2007, and the application numbers are 200410073298.5 and 200610042919.2 respectively. Summary of the invention

The object of the present invention is to provide cinnamon oil and its main component cinnamaldehyde in the preparation of anti-lung cancer Application in medicine.

In order to achieve the object of the present invention, the present invention provides an anti-lung cancer drug whose active ingredient is cinnamon oil and/or cinnamaldehyde, or a pharmaceutically acceptable salt, ester or amide thereof, or contains cinnamon oil and/or cinnamon. The aldehydes, or liposomes or nanoparticles of their pharmaceutically acceptable salts, esters or amides, optionally contain an appropriate amount of excipient.

The aforementioned anti-lung cancer drug is prepared from the following raw materials by weight:

Component I 0.5-10

Excipients 9.5-90;

Wherein component I is cinnamon oil and/or cinnamaldehyde, or a pharmaceutically acceptable salt, ester or amide thereof, or comprises cinnamon oil and/or cinnamaldehyde, or a pharmaceutically acceptable salt, ester or amide thereof. Liposomes or nanoparticles;

The pharmaceutically acceptable salt, ester or amide is a potassium salt, a sodium salt, a methyl ester, an ethyl ester, a benzyl ester or an amide of cinnamon oil and/or cinnamaldehyde, and the excipient is a binder, a filler, a lubricant, At least one of an antioxidant, a flavoring agent, a solubilizer, a solubilizer, an emulsifier or a dispersing agent.

The anti-lung cancer drug can be prepared into a dosage form such as a powder, a tablet, a pill, a capsule, a soft capsule, a nanoparticle, a mixture, an emulsion or an injection.

Listed several methods for preparing the above-mentioned anti-lung cancer drugs:

First, the quality of the drug substance is tested: Take the cinnamon oil and/or cinnamaldehyde aldehyde raw material, and refer to the Chinese Pharmacopoeia 2010 edition of a P378 cinnamon oil gas chromatographic method to detect the content of cinnamaldehyde in the cinnamon oil and / or cinnamaldehyde aldehyde raw materials. The content of cinnamaldehyde in cinnamon oil must not be less than 75%; the content of cinnamaldehyde in cinnamaldehyde aldehyde raw materials should not be lower than 98%.

Then, the preparation of a salt, an ester, an amide, a liposome or the like of cinnamon oil and/or cinnamaldehyde is carried out: according to the parts by weight, the certified cinnamon oil and/or cinnamaldehyde drug substance is taken according to the pharmaceutically acceptable salt, The ester or amide, the cinnamon oil and / or cinnamaldehyde are prepared as potassium or sodium salt, methyl ester / or ethyl / / benzyl ester, amide, liposome, the specific preparation method is as follows:

A. Preparation of cinnamic aldehyde amino acid Schiff base potassium salt: Take potassium glycinate in a reaction vessel, add methanol to prepare potassium glycinate potassium solution, pass nitrogen protection, and add qualified parts by weight at room temperature. Cinnamon oil and / or cinnamaldehyde aldehyde raw materials, while stirring After the completion of the dropwise addition, the reaction was continued at room temperature for 30 minutes until a white solid precipitated, and the reaction was kept for 2 hours. The solution was light red, filtered, and the solid was washed with anhydrous diethyl ether to dryness in vacuo to give cinnamaldehyde amino acid Schiff. Alkaline potassium salt.

B. Preparation of methyl cinnamate: Cinnamaldehyde and methanol are used to synthesize methyl cinnamate under the conditions of a catalyst. Using V ₂ 0 ₅ /H ₂ 0 ₂ as a catalyst, the yield was 95%; using PhI(OCOC3⁄4) ₂ /1 ₂ as a catalyst, the yield was 83%.

C. Preparation of ethyl p-methoxycinnamate: Take 7.2 g (0.04 moL) of p-methoxybenzoic acid, 24 mL (0.4 mol) of ethanol and lg of p-toluenesulfonic acid in a 100 mL Erlenmeyer flask and reflow Condensate tube, start magnetic stirring, water heating, reflux reaction for 2.5h. Slightly cold, switch to a distillation unit and distill off excess ethanol (recycled) on the water. After cooling, the reaction product was poured into ice water, and a large block of milky white solid was gradually precipitated. The solid matter was finely filtered by suction, and separately soaked with water, Na ₂ CO ₃ solution and water, washed, dried, and dried to obtain 7.5 g of milky white. Solid, yield 91%. The solid was dissolved in an appropriate amount of diethyl ether to further purify. The ether layer was washed thoroughly with Na ₂ CO ₃ solution, washed with water until neutral. Na ₂ S0 _{4 was} dried overnight. Na ₂ S0 _{4 was} filtered off, and ether was evaporated on water. The object is cooled and the white crystals are gradually precipitated.

D. Preparation of benzyl cinnamate: 50 mL of distilled water, 0.05 mol of sodium cinnamate (made with equimolar cinnamic acid and sodium hydroxide), 0.06 mol of benzyl chloride, a certain amount of catalyst (tetrabutyl) The 250 mL flask of ammonium chloride was placed in a modified microwave oven. The spherical condenser tube was connected to the round bottom flask through a small hole in the top of the microwave oven. After a certain period of microwave irradiation with a certain power, it was allowed to stand and cooled to room temperature. The liquid was poured into a separatory funnel, allowed to stand for stratification, and the organic phase was washed with water until neutral. After evaporation of excess benzyl chloride by steam distillation, the unreacted sodium cinnamate was removed to obtain a crude product. The crude product was subjected to vacuum distillation, and a fraction of 220-245 ° C / 2926 Pa was collected first, followed by distillation under reduced pressure, and a fraction of 228-230/2926 Pa was collected to obtain a pure product.

E. Preparation of cinnamamide: In a three-necked flask equipped with a stirrer and a thermometer, 15.5 g (0.25 moL) of ethanol and 18 mL of tetrahydrofuran were added, and 20.8 g (0.125 mol) of cinnamoyl chloride and 20 mL of tetrahydrofuran were prepared with stirring. The mixture is added to the reaction flask, when smoke is generated and the temperature rises. The temperature of the reaction system is controlled to 10 by cold water. °C -15 °C, after the completion of the dropwise addition, continue to stir the reaction for 30 min, then pour the reaction solution into 120 mL-150 mL of ice water-hydrochloric acid mixture, solid matter is precipitated, the solid is filtered off, dried, 150 mL of crude product Ethyl acetate was recrystallized to give a white solid product.

Formulation molding: taking cinnamon oil and/or cinnamaldehyde drug substance, or a pharmaceutically acceptable salt, ester or amide thereof, or containing cinnamon oil and/or cinnamaldehyde, or a pharmaceutically acceptable salt, ester or amide thereof Liposomes or nanoparticles, as well as one or more excipients, are prepared in accordance with the general guidelines for the preparation of various formulations clinically useful for the treatment of non-small cell lung cancer diseases.

In the present invention, MTT and other methods have confirmed that cinnamon oil and its main component cinnamaldehyde have significant inhibitory effects on non-small cell lung cancer cells A549, while cinnamic acid, the end product of cinnamic aldehyde, has no or only weak inhibition on A549. The role of cinnamon oil and its main component cinnamaldehyde has been developed as a drug for the treatment of non-small cell lung cancer. The advantages are as follows: meat cassia oil and its main component cinnamaldehyde aldehyde raw materials are very rich, the price is low, the toxic and side effects are small, the dosage form is easy to select, the preparation ingredients are clear, the preparation process and the quality standard are easy to control, and have good market compliance. DRAWINGS

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a graph showing growth curves of different concentrations of cinnamon oil on non-small cell lung cancer cells A549 in Example 1 of the present invention.

Fig. 2 is a graph showing growth curves of different concentrations of cinnamaldehyde to non-small cell lung cancer cells A549 in Example 1 of the present invention.

Fig. 3 is a graph showing growth curves of different concentrations of cinnamic acid on non-small cell lung cancer cells A549 in Example 1 of the present invention.

Fig. 4 is a graph showing the growth curve of 0.05 mg/mL cisplatin injection positive control group for non-small cell lung cancer cell A549 in Example 1 of the present invention.

Fig. 5 is a view showing the results of HPLC detection of the supernatant collected according to the MTT method in Example 1 of the present invention; wherein, the peak corresponding to 5.429 is cinnamic acid, and the peak corresponding to 8.277 is cinnamaldehyde.

Figure 6 is a collection of supernatants according to the MTT method for HPLC detection according to Example 1 of the present invention. 7 is a result of HPLC detection of the supernatant collected according to the MTT method in Example 1 of the present invention; wherein, the peak corresponding to 5.613 is a cinnamic acid standard.

8 is a result of HPLC detection of the supernatant collected according to the MTT method in Example 1 of the present invention; wherein, the peak corresponding to 5.650 is cinnamic acid, and the peak corresponding to 8.461 is cinnamic aldehyde.

Fig. 9 shows the results of HPLC detection of the supernatant collected according to the MTT method in Example 1 of the present invention; wherein, the peak corresponding to 5.615 is cinnamic acid, and the peak corresponding to 8.450 is cinnamaldehyde.

Fig. 10 shows the results of HPLC detection of the supernatant collected according to the MTT method in Example 1 of the present invention; wherein, the peak corresponding to 5.655 is cinnamic acid, and the peak corresponding to 8.469 is cinnamaldehyde. detailed description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art, and the raw materials used are all commercially available products.

Example 1 Experimental study on the effects of cinnamon oil, cinnamaldehyde and cinnamic acid on non-small cell lung cancer cell line A549

1.1 Materials and sources

Non-small cell lung cancer cells A549 was purchased from the Institute of Oncology, Chinese Academy of Medical Sciences.

1.2 Experimental methods

单 Monoclonal cultured cells A549 were digested with 0.25% trypsin, and RPMI1640 medium containing 10% fetal bovine serum was used to prepare a single cell suspension, and about 10 ⁴ cells per well were seeded in a 96-well culture plate. 100μΙ^. The plate was placed in a C0 ₂ incubator and incubated for one day at 37 ° C, 5% CO ₂ and saturated humidity.

Cinnamon oil, cinnamaldehyde and cinnamic acid were formulated to a final concentration of 0.05%, 0.04%, 0.03%, 0.02% and 0.01%. The positive control group was the clinical application of cisplatin injection (Nanjing Pharmaceutical Co., Ltd.). 0.05 mg/mL, the vehicle was RPMI1640 medium without fetal bovine serum.

After one day of cell culture, according to the three prepared reagents, 5 concentrations of each reagent were added to 96-well cell culture plates, and 4 replicate wells were added for each concentration. ΙΟΟμΙ^ was added to each well, and then placed on C0 ₂ incubator, cultured at 37 ° C, 5% C0 ₂ and saturated humidity 11 small Then, MTT solution (5mg/mL) 20μ was added to each well, and incubation was continued for 4 hours at 37 °C. The culture was terminated, and the culture supernatant in the well was discarded. 150 L of DMSO was added to each well, and the mixture was shaken for 10 min to fully dissolve the formazan. . The wavelength of 490 nm was selected, and the light absorption value of each well was measured on an enzyme-linked immunosorbent detector (Table 1 - Table 4). The cell growth curve was plotted on the horizontal axis and the light absorption value (A) was plotted on the vertical axis (Fig. 1). -Figure 4 ).

MTT detection light absorption value of A549 with different concentrations of cinnamon oil (A/490nm)

Concentration ( % )

Hole

Blank 0.01 0.02 0.03 0.04 0.05

1 1.295 1.196 0.511 0.323 0.24 0.207

2 1.238 1.441 0.555 0.345 0.264 0.235

3 1.113 1.403 0.463 0.358 0.256 0.255

4 1.022 1.345 0.433 0.365 0.257 0.206 Average 1.167 1.346 0.490 0.347 0.254 0.225 Table 2 MTT detection light absorption value of A549 with different concentrations of cinnamaldehyde (A/490nm)

Concentration ( % )

Hole

Blank 0.01% 0.02% 0.03% 0.04% 0.05%

1 1.473 0.902 0.259 0.208 0.211 0.163

2 1.355 0.871 0.27 0.295 0.281 0.235

3 1.353 1.028 0.303 0.282 0.277 0.214

4 1.355 0.998 0.332 0.278 0.266 0.212 Average 1.384 0.94975 0.291 0.26575 0.25875 0.206 Table 3 MTT detection of different concentrations of cinnamic acid on A549 (A/490nm)

Concentration ( % )

Blank 0.01% 0.02% 0.03% 0.04% 0.05%

1 1.171 1.516 1.511 2.099 2.073 1.018

2 1.000 1.08 1.535 1.862 1.976 0.98

3 1.027 1.032 1.474 0.941 1.16 1.013

4 1.187 1.101 1.522 1.102 1.037 1.002 Average 1.096 1.182 1.510 1.501 1.561 1.003 Table 4 Light absorption of MTT detection of A549 by cisplatin injection (A/490nm)

Double hole 3⁄4 0 cisplatin (concentration 0.05mg/mL)

1 0.63 0.254

2 0.599 0.243 3 0.558 0.247

4 0.535 0.264

Average 0.5805 0.252

From Table 1 to Table 4 and their corresponding cell growth curves, it can be seen that by comparing the positive control group cisplatin injection, cinnamon oil and its main component cinnamaldehyde have a significant inhibitory effect on A549, and the optimal concentration is 0.05. %; cinnamic acid does not produce or produces a very weak inhibitory effect. Cinnamon oil and cinnamaldehyde are unstable in the body and can be further metabolized into cinnamic acid. It is known that cinnamon oil and cinnamic aldehyde are inhibited by A549, and the metabolic end product cinnamic acid has no or only weak inhibition effect on A549.

Cinnamon oil, cinnamaldehyde and cinnamic acid were formulated into a 0.05% solution. The cells were cultured in 96-well culture plates according to the MTT method. The supernatants of the cells cultured for 3 hours were collected and centrifuged at 1000 °C for 10 min. The supernatant was taken for HPLC detection, and the mobile phase was acetonitrile-0.3% phosphoric acid = 1:1 (v/v). The peak time was recorded and the components and their contents were further analyzed.

Cinnamon oil and cinnamaldehyde are unstable in the body and can be further metabolized to cinnamic acid. The comprehensive MTT results (Fig. 5 - Fig. 10) show that after 3 hours of reaction, both cinnamon oil and cinnamaldehyde act and cinnamic acid peak appears, but There was no significant difference between the cinnamic acid and the standard map, suggesting that the inhibition of A549 is cinnamon oil and cinnamaldehyde, and its metabolic end product, cinnamic acid, has no or only weak inhibition on A549.

The above experimental results show that cinnamon oil and its main component cinnamaldehyde have a significant inhibitory effect on non-small cell lung cancer cell A549, and have the prospect of being developed into a drug for treating lung cancer.

Example 2 Preparation of Cinnamon Oil and/or Cinnamaldehyde Solid Preparation

1.1 Cinnamon oil and / or cinnamaldehyde microcapsules: 釆 adjust the pH method, take appropriate amount of gelatin and gum arabic dissolved and mix, add a specified part by weight of cinnamon oil and / or cinnamaldehyde, mixed with a high-speed dispersing machine, then transfer Into another container, dilute with distilled water to the desired concentration, stir at 40 ° C, and add 10% acetic acid solution to adjust the system to pH 4-5. After 15 minutes of constant temperature, ice water is cooled down to about 10 °C. The pH was adjusted to 6.0 by a 10% sodium hydroxide solution, and glutamine transaminase was added to assimilate the microcapsules to obtain a microcapsule dispersion. After suction filtration, washing with water, the wet microcapsule dispersion is obtained, and spray-dried to obtain cinnamon oil and/or cinnamon. Phenaldehyde microcapsules.

1.2 Cinnamon oil and / or cinnamaldehyde β-cyclodextrin inclusion complex: Solvent with ethanol, acetone, iso-alcohol and ethyl acetate as cinnamon oil. Add β-cyclodextrin (β-CD) to a saturated solution at 90 ° C in distilled water, slowly add the solvent-dissolved cinnamon oil at 800 r / min (the ratio of β-CD to cinnamon oil is 13:1), stir for lh, then refrigerate in the refrigerator for 24 h, filter, and wash with a small amount of distilled water to wash off some un-encapsulated β-CD, vacuum dry for 24h, grind, pass 80 mesh sieve to get thick Inclusion compound. The crude clathrate was washed three times with ethyl acetate and then air-dried to obtain a loose white clathrate powder.

1.3 Detection of cinnamaldehyde content in solid microcapsules: According to the Chinese Pharmacopoeia 2010 edition, an appendix VIE "gas chromatography", the content of cinnamaldehyde in solid microcapsules and clathrate powder was determined.

1.4 Preparation of preparations: According to the "Chinese Pharmacopoeia" 2010 edition of an Appendix I "General Preparations", suitable excipients, such as starch and / or lactose, can be used to prepare soft materials, which are separately prepared with cinnamaldehyde as a marker. Preparation of pills, powders, granules, tablets, capsules, and the like.

Example 3 Preparation of Liquid Preparation of Cinnamon Oil and/or Cinnamaldehyde

1.1 Cinnamon oil and / or cinnamaldehyde solution: At room temperature, take cinnamon oil and / or cinnamaldehyde in a container, add appropriate amount of cosolvent / or solubilizer, dispersant, etc., and then slowly add distilled water At the beginning, the system is less viscous. As the water volume increases, the system gradually becomes viscous and turbid. Continue to add distilled water and stir until the system is thick, turbid, and clarified. Containing cinnamon oil and/or cinnamaldehyde solution; record the amount of water added at this time.

1.2 Liposomes containing cinnamon oil and/or cinnamaldehyde: can be prepared by any of the methods of membrane/injection/freeze-thaw. For example, at room temperature, take cinnamon oil and / or cinnamaldehyde, excipients such as phosphorus materials in a container, add a solvent such as ethanol or a mixture, mix, remove the organic solvent, collect the film in the container, use distilled water Or the buffer solution dissolves the membrane, homogenizes, stirs, vortexes or sonicates to obtain liposomes.

1.3 Determination of cinnamaldehyde content in cinnamon oil and / or cinnamaldehyde solution or liposome: The Chinese Pharmacopoeia 2010 edition of an appendix VIE "gas chromatography" to detect cinnamaldehyde content.

1.4 Formulation: According to the Chinese Pharmacopoeia 2010 edition, Appendix I, “General Preparations”, appropriate amount of flavoring agent and/or emulsifier and/or dispersing agent may be added to prepare cinnamic aldehyde as the labeling content. Preparation of mixture, dropping pills, injections and the like.

Although the present invention has been described in detail with reference to the preferred embodiments of the present invention, it will be apparent to those skilled in the art. Therefore, such modifications or improvements made without departing from the spirit of the invention are intended to be within the scope of the invention. Industrial applicability

The present invention has been confirmed by MTT and the like that cinnamon oil and its main component cinnamaldehyde have significant inhibitory effects on non-small cell lung cancer cell A549, and cinnamic acid, a metabolic end product of cinnamaldehyde, has no or only weak inhibition effect on A549. . Cinnamon oil and its main component cinnamaldehyde can be used in the preparation of anti-lung cancer drugs. The raw materials are rich, the price is low, the toxic and side effects are small, the dosage form is easy to select, the preparation ingredients are clear, the preparation process and quality standards are easy to control, and the market is well-adapted. Sex and application prospects.

Claims

Claim

1. The application of cinnamon oil and its main component cinnamaldehyde in the preparation of anti-lung cancer drugs.

An anti-lung cancer drug whose active ingredient is cinnamon oil and/or cinnamaldehyde, or a pharmaceutically acceptable salt, ester or amide thereof, or contains cinnamon oil and/or cinnamaldehyde, or they are pharmaceutically acceptable a salt, ester or amide liposome or nanoparticle, optionally containing

The anti-lung cancer drug according to claim 2, which is produced from the following raw materials in a weight:

Component I 0.5-10

Excipients 9.5-90;

The anti-lung cancer drug according to claim 2 or 3, wherein the drug is prepared as a powder, a tablet, a pill, a capsule, a nanoparticle, a mixture, an emulsion or an injection.