CN106139151A

CN106139151A - Ascorbic acid palmityl ester and the synergistic pharmaceutical composition of antitumor drug

Info

Publication number: CN106139151A
Application number: CN201610294298.0A
Authority: CN
Inventors: 卢杨; 王子厚; 杨越; 陈西敬; 赵娣; 李宁; 陈琪; 马恩龙; 张玲
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-04-29
Filing date: 2016-04-29
Publication date: 2016-11-23

Abstract

The present invention relates to a kind of medicine treating malignant tumor, vitamin C palmityl ester cancer therapy drug in particular for administrations such as intravenous injection and oral or intratumor injections, it share with vitamin C palmityl ester or with one or more other chemotherapeutics, is prepared as pharmaceutically acceptable injection or oral dosage form.The medicine of the present invention, there are excellent physical and chemical stability and definite antitumor action, cell assay in vitro and tumor-bearing mice test show, this medicine or a combination thereof thing are effective to Several Kinds of Malignancies such as breast carcinoma, hepatocarcinoma, pulmonary carcinoma, gastric cancer, cancer of pancreas, cervical cancer, glioma, carcinoma of prostate, colorectal cancers.

Description

Ascorbic acid palmityl ester and the synergistic pharmaceutical composition of antitumor drug

Technical field

The present invention relates to a kind of medicine treating malignant tumor, in particular for intravenous injection and oral or intratumor injection etc. The vitamin C palmityl ester cancer therapy drug of administration, it is with vitamin C palmityl ester or and one or more other chemotherapeutic Thing share, and is prepared as pharmaceutically acceptable injection or oral dosage form.The medicine of the present invention, has excellent physical chemistry steady Qualitative and definite antitumor action, cell assay in vitro and tumor-bearing mice test show, this medicine or a combination thereof thing are to mammary gland The Several Kinds of Malignancies such as cancer, hepatocarcinoma, pulmonary carcinoma, gastric cancer, cancer of pancreas, cervical cancer, glioma, carcinoma of prostate, colorectal cancer are effective.

Background technology

Vitamin C (Vitamin C) is also known as ascorbic acid (Ascorbic acid), and chemical molecular formula is C₆H₈O₆.It is Nineteen twenty-eight is separated by Hungary scientist first with Nobel chemistry Prize winner Szent-Gyorgyi and reports^[1], chemistry knot Structure formula is as shown in Equation 1.Vitamin C has the most important physiological function^[2], such as, can promote collagen by activating hydroxylase The generation of albumen；Can be by the Fe in food³⁺It is reduced to Fe²⁺, promote that human body is to Fe²⁺Absorption, prevent and to treat iron-deficient lean Blood；Oxidized form of glutathione can be made under the effect of glutathion reductase to be reduced to reduced glutathion, be conducive to maintaining The integrity of cell membrane；Acid medium can be formed in digestive tract, prevent the generation of insoluble calcium complex, promote dietary calcium Absorb, be beneficial to maintain skeleton and the normal function of tooth.

Result of study shows, the vitamin C of low dosage is a kind of antioxidant, participates in internal multiple enzymatic reaction process, It it is the important substance of the activity of sustaining life.The vitamin C of high dose then has Oxidation, Fe in tumor cell³⁺Catalysis Under can produce H₂O₂And play and kill tumor cell effect.Since 20 century 70s, ascorbic antitumor action causes Relatively broad concern.Initially by American scientist L.Pauling and cancer expert E.Cameron according to the most existing one A little epidemiologic datas, animal experiment and clinical trial propose the vitamin C Therapeutic Method of cancer^[3].Subsequently, more and more Experiment show, vitamin C can the most anti-curing oncoma, kinds of tumor cells is had Selective depression and kill make With^[4].Additionally, vitamin C also can strengthen the antitumor activity (+vitamin C patent No.), the poison reducing antitumor drug is secondary Effect.The mechanism of action of vitamin C treatment tumor mainly includes three below aspect^[5]: the dimension of (1) intravenous injection pharmacology concentration Raw element C is as H₂O₂Prodrug be transported to extracellular fluid, extracellular produce H₂O₂After, H₂O₂Cell membrane, extracellular can be passed through H₂O₂Enter cell membrane lipids, form H₂O₂Or intermediate product, in normal cell, these products can be eliminated, but quick The tumor cell of sense but cannot be eliminated, and then the effect of selective killing tumor cell can be played^[6].(2) vitamin C Can affect the expression of tumor death related gene P53, C-myc, Bcl-2, in suppression tumor cell, the synthesis of DNA complex, dry Disturb the tumor cell metabolism cycle, the differentiation of inducing tumor cell, limit the growth of tumor cell, promote withering of tumor cell Die^[7].(3) vitamin C can suppress to cause the generation of the material nitrosamine of gastric cancer, the esophageal carcinoma with amine competition binding nitrate^[8]。

But vitamin C implements comparison as chemotherapeutic or adjuvant chemotherapy medicine for the treatment of clinical tumor disease is stranded Difficulty, is on the one hand because ascorbic polarity relatively big, is difficult to play antitumor action through cell membrane, so its active anticancer Relatively low, to most of cancerous cell IC₅₀More than 1000 μMs (+vitamin C patent No.s), clinical required dosage is relatively big, according to report Road patient injects 20～50g vitamin C competence exertion curative effects every day, and patient compliance is poor, and clinic is difficult to carry out；On the other hand The chemical property extremely unstable of vitamin C self, company's enediol structure special in molecular structure makes it at aqueous solution and air In be oxidized easily and be degraded to dehydrogenation type ascorbic acid, particularly light, micro heavy and fluorescent materials etc. more can promote its oxygen Change, cause its fast degradation to lose physiologically active.The targeted drug such as nanometer, liposome should not be made and improve curative effect, it is also difficult to Make compound preparation with other chemotherapeutic and play potentiation.This makes vitamin C application in terms of clinical antineoplastic receive Considerable restraint.One of way solving this problem is to increase its stability by transformation vitamin C chemical constitution.Such as, may be used Make derivative of fatty acid, the shortcoming that vitamin C is unstable can be overcome, can preferably play again ascorbic physiology merit Energy^[9]。

Vitamin C palmityl ester (L-palmitoyl ascorbate, PA) is also known as L-AA palmityl ester, molecule Formula is C₂₂H₃₈O₇, as shown in Equation 2, natural vitamin C palmityl ester is present in the plant amedica such as Fructus Lycii or food materials to chemical structural formula In, its synthetic can trace back to nineteen forty-three the earliest, for U.S. Swern et al. by ascorbic C6 position OH and a part Petiolus Trachycarpi Acid is dehydrated into what ester generated^[10].Implantation due to Palmic acid so that it is existing hydrophilic ascorbyl, has again the palm fibre of oleophylic Palmitic acid acyl ester, thus become a kind of excellent antioxidant.Due to vitamin C with Palmic acid be all in food naturally occurring become Point, so its safety is high, be the most widely used as in the feed additive of Aquatic product and aquaculture, food and medicine is anti- Oxidant, the brightening agent etc. of cosmetics, a kind of being allowed to of its Ye Shi China adds the antioxidant in baby food.According to system Meter, the whole world is about 5000 tons to the usage amount of vitamin C palmityl ester at present every year.

Although vitamin C palmityl ester uses many as the antioxidant of feed additive or food and medicine and cosmetics Year, and included to American Pharmacopeia (The United States Pharmacopeial Convention 35) and Europe Pharmacopeia (EUROPEAN PHARMACOPOEIA 8.0) is applied as pharmaceutic adjuvant, but which country does not the most still have by it Medicine as medicine, especially anticancer usage.Both do not became as primary treatment on medical market both at home and abroad Divide pharmaceutical preparation, do not see corresponding clinical practice or clinical research report.

Vitamin C palmityl ester is prepared as targeting preparation

Anti-tumor activity about vitamin C palmityl ester, although at present existing the most a small amount of about cell or animal experiment Fragmentary report^{[38,39,40,54,61,101,102]}, but its result of study is still insufficient as vitamin C palmityl ester and prepares antitumor The foundation of medicine, makes a concrete analysis of as follows: 1, less for studying the cell strain kind of its drug effect, only breast carcinoma, ovarian cancer, kidney Cancer, ehrlich ascites carcinoma, skin carcinoma, leukemia etc. totally 7 kinds, and to the most common breast carcinoma, hepatocarcinoma, pulmonary carcinoma, gastric cancer, cancer of pancreas, Cervical cancer, glioma, carcinoma of prostate, colorectal cancer, oral epithelium cancer, lymphatic cancer, esophageal carcinoma, melanoma A375, bladder Cancer, nasopharyngeal carcinoma etc. are not yet reported；2, the not strong (IC of the anti-tumor activity of vitamin C palmityl ester in its result of study₅₀＞ 1000 μ M), without clear superiority compared with vitamin C, the result (IC studied with this₅₀＜ 200 μMs) differ relatively big, estimate its research process The concentration of middle vitamin C palmityl ester is lower than labelled amount, and its reason may cause it for dissolving is incomplete or placement condition is improper Oxidized or degraded；Although 3 reports [38] also having vitamin C palmityl ester liposome, but its formulation of drug and adjuvant The ratio of ratio and C/PL is improper and in placement process, vitamin C palmityl ester is oxidized easily.The document is tieed up Raw element C palmityl ester mol ratio shared by prescription is 30mol% (conversion is 34.6% for mass ratio), the study show that this Ratio is excessive, and the liposome encapsulation prepared is low, and in placement process, vitamin C palmityl ester easily separates out；Cholesterol Ratio too high (phospholipid: cholesterol=70: 30mol% is 2: 1, w/w), this can cause liposome film to form difficulty, film Insecure destructible thus cause inclusion to leak, the preparation obtained is owing to envelop rate is low and poor stability, it may be possible to its cell The main cause that in result of the test, active anticancer is poor；Although 4 documents also have vitamin C palmityl ester and amycin^[61]Or Paclitaxel^[45]Share the report making compound preparation, but in its prescription, the content of vitamin C palmityl ester is the most relatively low, does not reaches The purpose of Synergistic.The Rambhau professor Devraj report of Ka Ka Dalmatia university of India (Kakatiya University) Road^[61]A kind of compound recipe Liposomal formulation of vitamin C palmityl ester and amycin, its vitamin C palmityl ester: amycin (DOX) ratio is 0.6: 1 (w/w), (note: in its 10mL preparation the palmityl ester Han vitamin C be 15mg, DOX be 25mg (2.5mg/mL), so vitamin C palmityl ester: DOX=15: 25=0.6: 1, w/w).And Northeast USA university Vladimir P professor Torchilin etc. reports the compound recipe lipid system of a kind of vitamin C palmityl ester and paclitaxel Agent^[40,54], vitamin C palmityl ester: the ratio of paclitaxel is 20: 3.4=5.88: 1 (w/w) or 10: 2=5: 1 (w/w) (ginseng See document Fig. 5: PCT loaded PA-liposomes (20mg/kg of PA and 3.4mg/kg of PCT), and document Fig. 6: (10mg/kg of PA and 2mg/kg of PCT).

The theoretical foundation of the present invention is, using vitamin C palmityl ester as the fat-soluble prodrug of ascorbic one, due to Its lipotropy after hydroxy esterification in vitamin C molecules is strengthened, so it is easier to enter tumor theoretically Cell, if the energy substantial amounts of vitamin C of hydrolysis under the effect of enzyme, it is possible to play the curative effect more higher than vitamin C.

The purpose of patent of the present invention is exactly as the fat-soluble prodrug of ascorbic one using vitamin C palmityl ester, greatly Its application in preparing antitumor drug is illustrated on the basis of quantity research.

The study show that, the vitamin C palmityl ester IC to most of tumor cells₅₀Less than 200 μMs (see accompanying drawing *～ Table *), and the IC that vitamin C is to tumor cell₅₀Then more than 1000 μMs (+vitamin C patent No.), so its curative effect and vitamin C Compare and can improve more than 10 times.

The study show that, other antitumor drug is share by vitamin C palmityl ester has obvious potentiation synergism, Potentiation to most of antineoplastic agents reaches more than 10 times (seeing attached list *～table *).

The another advantage of vitamin C palmityl ester is that its chemical property is the most stable, with air short term contact not The most oxidized, thus can be made into the targeted drug such as nanometer formulation or liposome, it is possible to make compound preparation with its chemotherapeutic and play The purpose of efficacy enhancing and toxicity reducing.

List of references

[1] Grzybowski A, Pietrzak K.Albert(1893-1986): The Scientist who discovered vitamin C [J] .Clinics in Dermatology, 2013,31 (3): 327- 331.

[2] Zeng Xiangyun. ascorbic physiological function and meals guarantee. [J]. and Chinese food and nutrition, 2005,4:52- 54.

[3]Cameron E and Pauling L.Cancer and Vitamin C Linus Pauling Institute of science and medicine, Mendio Park, California 1979.

[4] M.W.Roomi, D.House, M.Eckert-Maksic, Z.B.Maksic, C.S.Tsao, Growth suppression of malignant leukemia cell line in vitro by ascorbic acid(vitamin C) and its derivatives. [J] .Cancer Letter 1998 (122): 93-99.

[5] Jing Xiaojuan. vitamin C Effect study progress in oncotherapy. [J]. and Medical review .2010,16 (4): 555-556.

[6] Chen Q, Espey MG, Krishna MC, etal.Pharmacologic ascorbic acid concentrations selectively kill cancer cells action as a pro-drug to deliver hydrogen peroxide to tissues.

[7] Kang Jiu-Hong, SHI Yi-Min, ZHENG Rong-Liang, Effects of ascorbic acid on human hepatoma cell proliferation and redifferentiation.[J].Acta Pharmacol Sin.1999,20 (11): 1019-1024.

[8] Zhu Yufei. the carcinogenesis of nitrosamine compound and prevention. [J]. environmental conservation and recycling economy .2008: 34-35.

[9] rich Jian Hua. the progress of AA2G analog derivative. [J] .Chinese Journal of New Drugs 2012,21 (7): 761-763.

[10] Sapper H, Cameron D G, Mantsch H H.The thermotropic phase behavior Of ascorbyl palmitate:an infrared spectroscopic study [J] .Canadian Journal of Chemistry, 2011,59:2543-2549.

[38] Sawant R R, Vaze O S, WangT, et al.Palmitoyl ascorbate liposomes and Free ascorbic acid:comparison of anticancer therapeutic effects upon Parenteral administration. [J] .Pharrnaceutical Research, 2012,29 (2): 375-383 (9).

[39] Sawant R R, Vaze O, D ' Souza G G M, et al.Palmitoyl ascorbate-loaded Polymeric micelles:cancer cell targeting and cytotoxicity. [J] .Pharmaceutical Research, 2011,28 (2): 301-308.

[40] Sawant R R, Vaze O S, Rockwell K, et al.Palmitoyl ascorbate-modified liposomes as nanoparticle platform for ascorbate-mediated cytotoxicity and paclitaxel co-delivery[J].European Journal of Pharmaceutics&Biopharmaceutics Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E V, 2010,75 (3): 321-326.

[54] D ' Souza G G M, Wang T, Rockwell K, et al.Surface modification of pharmaceutical nanocarriers with ascorbate residues improves their tumor-cell association and killing and the cytotoxic action of encapsulated paclitaxel In vitro [J] .Pharmaceutical research, 2008,25 (11): 2567-2572.

[61] Jukanti R, Devraj G, Shashank A S, et al.Biodistribution of ascorbyl palmitate loaded doxorubicin pegylated liposomes in solid tumor bearing mice [J] .Journal of microencapsulation, 2011,28 (2): 142-149.

[101] Chen Peng. vitamin C is the study on the synthesis [D] of the Brain targeting pharmaceutical carrier of hydrophilic fragments. Beijing chemical industry is big Learn, 2010..

Gu Xuexian. the preparation of vitamin C derivatives and the application [J] in cosmetics thereof. chemical reagent, 2011, (4): 325-328.

Summary of the invention

Present invention aims to the treatment of current clinical cancer, particularly treat in the existing medicine of malignant tumor The shortcoming that systemic side effects is big, targeting is poor existed, it is provided that the newtype drug that a kind of determined curative effect, side effect are little, with injection Or oral dosage form.

For achieving the above object, the present invention uses following technical proposal:

A kind of medicine being mainly used in treating malignant tumor, is made up of active component and pharmaceutically acceptable adjuvant, activity Composition is vitamin C palmityl ester and one or more Common Chemotherapy medicines.The present composition includes vitamin C palmityl ester With one or more conventional tumor chemotherapeutic drugs；The compositions of the present invention can only have vitamin C palmityl ester and one or many Plant conventional tumor chemotherapeutic drug composition；Other active component can also be included.

The present invention selects vitamin C palmityl ester as the main anti-tumor composition in compound recipe, is equipped with clinical conventional, effect The clearest and the most definite chemotherapeutics, by different mechanism, the different physiological stages that simultaneously act on tumor cell, or direct killing tumor Cell, plays certain synergism, can effectively treat various malignant tumor.

The chemical drugs that vitamin C palmityl ester is the conventional safety of clinical oral administration, injection, compliance is good.Can kill Do not damage host cell while tumor cell, reach high selectivity, be substantially reduced the toxic and side effects of cancer therapy drug.The most originally In invention, the dosage of vitamin C palmityl ester should be greater than 0.1mg/mL.

Auxiliary therapeutic agent in compositions, selects the chemotherapeutics that clinic is conventional, by physics, chemistry compatibility mechanism, enters Row initial option, it is ensured that the chemical stability of reproducibility medicine vitamin C palmityl ester；Then tried by tumor cell in vitro strain Test, relatively the drug effect of each pharmaceutical composition, it is ensured that the two drug effect does not influences each other, and be improved chemotherapy effect, even collaborative work With；By tumor-bearing mice test, the drug effect of compositions is further investigated, use intratumor injection mode to be administered, observe tumor The indexs such as body size, thus determine the composition of this pharmaceutical composition.

Described clinic is commonly used tumor chemotherapeutic drug and all be can operate with the present invention, and conventional tumor chemotherapeutic drug includes but do not limits Due to antibiotics antineoplastic agent, anti-tumor botanical, anti-metabolism antineoplastic agent, platinum antineoplastic medicine, hormones antitumor Medicine, alkanisation class antineoplastic agent, biological immune class antineoplastic agent, cell-differentiation inducers, monoclonal antibody, Agiogenesis inhibition Agent, epidermal growth factor receptor antagonists, immunosuppressant.

Described antibiotics antineoplastic agent is mould selected from amycin, mitomycin, daunorubicin, actinomycin D, Pingyang Element, doxorubicin, pirarubicin, epirubicin；

Described anti-tumor botanical is selected from vincristine, vinorelbine, vindesine, paclitaxel, Docetaxel, first Isoindigo；

Described anti-metabolism antineoplastic agent replaces song selected from fluorouracil, methotrexate, cytosine arabinoside, capecitabine, thunder (its derivant of preferred camptothecine is selected for plug, gemcitabine, pemetrexed, hydroxyurea, 6-MP, camptothecin analogues From hydroxy camptothecin, irinotecan, topotecan)；

Described platinum antineoplastic medicine is selected from cisplatin, carboplatin, oxaliplatin；

Described hormones antineoplastic agent selected from dexamethasone, hydrocortisone, toremifene, exemestane, letrozole, Bicalutamide, progestogens (preferred progestogens medicine is selected from medroxyprogesterone, megestrol etc.), sex hormones are (preferably Sex hormone drug is selected from estrogen diethylstilbestrol etc.), androgen (preferred androgen medicine is selected from testosterone propionate etc.), promote Luteinizing hormone releasing hormone (preferred luteinizing hormone-releasing hormone medicine is selected from goserelin, leuprorelin etc.)；

Described alkanisation class antineoplastic agent is selected from cyclophosphamide, chlormethine, temozolomide；

Described biological immune class antineoplastic agent selected from interferon, tumor necrosis factor, thymosin, interleukin, she Imatinib, gefitinib, erlotinib, Sorafenib；

Described cell-differentiation inducers is selected from retinoic acid, arsenious acid；

Described monoclonal antibody drug is selected from Herceptin, Rituximab.

Selected from biological immune class antineoplastic agent, (preferred biological immune class antineoplastic agent selects other described class antineoplastic agent Self-interference element, tumor necrosis factor, thymosin, interleukin, imatinib, gefitinib, erlotinib, Sorafenib Deng), cell-differentiation inducers (preferred cell-differentiation inducers be selected from retinoic acid, arsenious acid etc.), monoclonal antibody (preferably Monoclonal antibody drug be selected from Herceptin, Rituximab), angiogenesis inhibitor, EGF-R ELISA antagonism Agent etc..

1., antibiotics antineoplastic agent and vitamin C palmityl ester be when share the medicine of preparation treatment cancer,

The molar ratio of antibiotics antineoplastic agent and vitamin C palmityl ester can be

1: 100～500 × 10³；Or preferably 1: 33～250 × 10³；Or 1: 1 × 10³～1 × 10⁶

Or preferably 1: 1.5 × 10³～750 × 10³Or preferably 1～300: 450 × 10³～750 × 10³

More preferably 1～300: 200 × 10³；Most preferably 1～100: 80 × 10³～200 × 10³

More preferably 1～300: 225 × 10³；Most preferably 1～100: 90 × 10³～225 × 10³

More preferably 1～300: 250 × 10³；Most preferably 1～100: 100 × 10³～250 × 10³

Or the molar ratio of antibiotics antineoplastic agent and vitamin C palmityl ester can be

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～100: 33333

More preferably 1～100: 41667；

More preferably 1～100: 50000；

2, when anti-tumor botanical and vitamin C palmityl ester share the medicine that cancer is treated in preparation,

The molar ratio of anti-tumor botanical paclitaxel and vitamin C palmityl ester may is that

1～64: 500～8333 × 10³；Preferably 1～32: 1 × 10³～8333 × 10³

More preferably 1～32: 40 × 10³～6667 × 10³；Most preferably 8～16: 40 × 10³～6667 × 10³

More preferably 1～32: 60 × 10³～7500 × 10³；Most preferably 16～32: 60 × 10³～7500 × 10³

More preferably 1～32: 80 × 10³～8333 × 10³；Most preferably 1～16: 80 × 10³～8333 × 10³

Or the molar ratio of anti-tumor botanical and vitamin C palmityl ester may is that

1: 10～1000 × 10³；Preferably 1: 1.5 × 10³～1000 × 10³；Further preferred: 1.8 × 10³～850 × 10³

More preferably 1～300: 450 × 10³～800 × 10³；Most preferably 1～30: 450 × 10³～1000 × 10³

More preferably 1～300: 900 × 10³；Most preferably 1～30: 600 × 10³～1250 × 10³

More preferably 1～300: 1000 × 10³；Most preferably 1～30: 750 × 10³～1500 × 10³

3, when anti-metabolism antineoplastic agent and vitamin C palmityl ester share the medicine that cancer is treated in preparation,

The molar ratio of anti-metabolism antineoplastic agent and vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；More preferably 1: 137.5～6800

More preferably 1～300: 3334～550 × 10³；Most preferably 1～10: 550 × 10³

More preferably 1～300: 4167～700 × 10³；Most preferably 1～10: 700 × 10³

More preferably 1～300: 850 × 10³～～5000 × 10³；Most preferably 1～33: 850 × 10³～5000 × 10³

Or the molar ratio of anti-metabolism antineoplastic agent and vitamin C palmityl ester may is that

1: 1～83333 or 1～333: 550～83333

Or preferably 1: 2.5～2833；Or preferably 1: 5.5～2833；Or preferably 1～333: 1833～2833

Or preferably 1～333: 833～1667；Or preferably 1～333: 66667～83333

More preferably 1～333: 550～66667；Most preferably 1～33: 550～66667

More preferably 1～333: 700～75000；Most preferably 1～33: 700～75000

More preferably 1～333: 850～83333；Most preferably 10～33: 850～83333

4, when platinum antineoplastic medicine and vitamin C palmityl ester share the medicine that cancer is treated in preparation,

The molar ratio of platinum antineoplastic medicine and vitamin C palmityl ester may is that

1∶30-20000；Or preferably 1: 33-15000；Or 1: 1～25000 or preferably 1: 2.5～2833；Or preferably 1～ 333: 833～1667

More preferably 1～333: 833～20000；Most preferably 1～100: 833～20000

More preferably 1～333: 1250～22500；Most preferably 1～100: 1250～22500

More preferably 1～333: 1667～25000；Most preferably 1～100: 1667～25000

Or the molar ratio of platinum antineoplastic medicine and vitamin C palmityl ester may is that

1∶1-900；Preferably 1: 5-480；

More preferably 8～64: 320；

More preferably 1～64: 400；

More preferably 1～64: 480；Further preferred 1～32: 480；

1: 5～20000 preferably 1: 15-20000；

Preferably 1: 15～10000 or preferably 1～300: 4500～10000

More preferably 1～300: 4500～10000；Further preferred 3～300: 4500～10000；Most preferably 100～300: 10000；

More preferably 1～300: 6000～12500；Further preferred 3～300: 6000～12500；Most preferably 100～300: 6000～12500；

More preferably 1～300: 7500～15000；Further preferred 3～300: 7500～15000；Most preferably 10～100: 7500～15000；

5, when alkanisation class antineoplastic agent and vitamin C palmityl ester share the medicine that cancer is treated in preparation,

The molar ratio of alkanisation class antineoplastic agent and vitamin C palmityl ester may is that

1: 1～5000；Preferably 1: 2.5～2833；Or preferably 1～333: 833～1667

More preferably 1～32: 8；Most preferably 2～8: 8

More preferably 1～32: 12；Most preferably 8～32: 12

More preferably 1～32: 16；Most preferably 8～32: 16

6, when biological immune class antineoplastic agent and vitamin C palmityl ester share the medicine that cancer is treated in preparation,

The molar ratio of biological immune class antineoplastic agent and vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～32: 3200

More preferably 1～32: 4000；Most preferably 2～4: 4000；

More preferably 1～32: 4800；Most preferably 1～4: 4800；

The technical scheme that is preferable to carry out of the present invention farther includes but is not limited to following technical scheme:

When 1.1 amycin and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of amycin and vitamin C palmityl ester can be

When 1.2 Bleomycin A5s and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of Bleomycin A5 and vitamin C palmityl ester can be

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～100: 33333

More preferably 1～100: 41667；

More preferably 1～100: 50000；

When 1.3 vincristine and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of vincristine paclitaxel and vitamin C palmityl ester may is that

1～64: 500～8333 × 10³；Preferably 1～32: 1 × 10³～8333 × 10³

When 1.4 paclitaxels and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma,

The molar ratio of paclitaxel and vitamin C palmityl ester may is that

When 1.5 gemcitabines and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of gemcitabine and vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；More preferably 1: 137.5～6800

When 1.6 hydroxy camptothecins and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of hydroxy camptothecin and vitamin C palmityl ester may is that

1: 1～83333 or 1～333: 550～83333

Or preferably 1～333: 833～1667；Or preferably 1～333: 66667～83333

More preferably 1～333: 550～66667；Most preferably 1～33: 550～66667

More preferably 1～333: 700～75000；Most preferably 1～33: 700～75000

More preferably 1～333: 850～83333；Most preferably 10～33: 850～83333

When 1.7 cisplatin and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of cisplatin and vitamin C palmityl ester may is that

More preferably 1～333: 833～20000；Most preferably 1～100: 833～20000

More preferably 1～333: 1250～22500；Most preferably 1～100: 1250～22500

More preferably 1～333: 1667～25000；Most preferably 1～100: 1667～25000

When 1.8 carboplatins and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of carboplatin and vitamin C palmityl ester may is that

1∶1-900；Preferably 1: 5-480；

More preferably 8～64: 320；

More preferably 1～64: 400；

More preferably 1～64: 480；Further preferred 1～32: 480；

When 1.9 oxaliplatins and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of oxaliplatin and vitamin C palmityl ester may is that

1: 5～20000 preferably 1: 15-20000；

Preferably 1: 15～10000 or preferably 1～300: 4500～10000

When 1.10 temozolomides and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of temozolomide and vitamin C palmityl ester may is that

1: 1～5000；Preferably 1: 2.5～2833；Or preferably 1～333: 833～1667

More preferably 1～32: 8；Most preferably 2～8: 8

More preferably 1～32: 12；Most preferably 8～32: 12

More preferably 1～32: 16；Most preferably 8～32: 16

When 1.11 Sorafenibs and vitamin C palmityl ester share the medicine of preparation treatment cancer,

The molar ratio of Sorafenib and vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～32: 3200

More preferably 1～32: 4000；Most preferably 2～4: 4000；

More preferably 1～32: 4800；Most preferably 1～4: 4800；

The more preferably enforcement technical scheme of the present invention farther includes but is not limited to following technical scheme: 1.1 amycin When share the medicine of preparation treatment people's hepatocarcinoma with vitamin C palmityl ester,

The molar ratio of amycin and vitamin C palmityl ester can be

1∶1×10³～500 × 10³；Preferably 1: 33～15 × 10³；

More preferably 33～333: 333 × 10³

More preferably 1～333: 417 × 10³；

More preferably 3.3～333: 500 × 10³；

When 1.2 Bleomycin A5s and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma,

The molar ratio of Bleomycin A5 and vitamin C palmityl ester can be

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～100: 33333

More preferably 1～100: 41667；

More preferably 1～100: 50000；

When 1.3 vincristine and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma,

The molar ratio of vincristine and vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～333: 333 × 10³

More preferably 1～333: 417 × 10³

More preferably 1～100: 500 × 10³；Further preferred 1～10: 500 × 10³

The molar ratio of paclitaxel and vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；

More preferably 30～300: 1000 × 10³

More preferably 1～300: 1250 × 10³

More preferably 1～300: 1500 × 10³；Further preferred 3～30: 1500 × 10³

When 1.5 gemcitabines and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma, gemcitabine and Wei Sheng The molar ratio of element C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～33: 3334

More preferably 1～33: 4167

More preferably 1～33: 5000 × 10³；Further preferred 6.7～33: 5000 × 10³；

When 1.6 hydroxy camptothecins and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma, hydroxy camptothecin and The molar ratio of vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；

More preferably 3～300: 10000

More preferably 1～300: 12500；

More preferably 1～300: 15000；

When 1.7 cisplatin and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma,

The molar ratio of cisplatin and vitamin C palmityl ester may is that

1∶30-20000；Preferably 1: 33-15000；

More preferably 30～1000: 10000；

More preferably 1～1000: 12500；

More preferably 1～1000: 15000；

When 1.8 carboplatins and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma,

The molar ratio of carboplatin and vitamin C palmityl ester may is that

1∶1-900；Preferably 1: 5-480；

More preferably 8～64: 320；

More preferably 1～64: 400；

More preferably 1～64: 480；Further preferred 1～32: 480；

When 1.9 oxaliplatins and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma,

The molar ratio of oxaliplatin and vitamin C palmityl ester may is that

1∶30-20000；Preferably 1: 33-15000；

More preferably 1～300: 10000；Further preferred 30～300: 10000；Most preferably 100～300: 10000；

More preferably 1～300: 12500；Further preferred 3～300: 12500；Most preferably 100～300: 12500；

More preferably 1～300: 15000；

When 1.10 Sorafenibs and vitamin C palmityl ester share the medicine of preparation treatment people's hepatocarcinoma,

The molar ratio of Sorafenib and vitamin C palmityl ester may is that

1∶10-30000；Preferably 1: 33-15000；

More preferably 1～32: 3200

More preferably 1～32: 4000；Most preferably 2～4: 4000；

More preferably 1～32: 4800；Most preferably 1～4: 4800；

When 2.1 vincristine and vitamin C palmityl ester share the medicine of preparation treatment people's pulmonary carcinoma,

The molar ratio of vincristine and vitamin C palmityl ester may is that

1∶1×10³～1088 × 10³

Preferably 1: 11 × 10³～1088 × 10³

Or preferably 1～64: 704 × 10³～1088 × 10³

More preferably 1～64: 704 × 10³；Most preferably select 1～32: 704 × 10³

More preferably 1～64: 896 × 10³；Most preferably 1～32: 896 × 10³

More preferably 1～64: 1088 × 10³；Most preferably 1～32: 1088 × 10³

When 2.2 paclitaxels and vitamin C palmityl ester share the medicine of preparation treatment people's pulmonary carcinoma,

The molar ratio of paclitaxel and vitamin C palmityl ester may is that

1∶1×10³～1 × 10⁶

Preferably 1: 1.8 × 10³～850 × 10³

Or preferably 1～300: 550 × 10³～850 × 10³

More preferably 1～300: 550 × 10³；Most preferably 1～10: 550 × 10³

More preferably 1～300: 700 × 10³；Most preferably 1～10: 700 × 10³

More preferably 1～300: 850 × 10³；Most preferably 1～10: 850 × 10³

When 2.3 gemcitabines and vitamin C palmityl ester share the medicine of preparation treatment people's pulmonary carcinoma,

The molar ratio of gemcitabine and vitamin C palmityl ester may is that

1: 50～10000

Preferably 1: 137.5～6800

Or preferably 1～32: 4400～6800

More preferably 1～300: 550 × 10³；Most preferably 1～10: 550 × 10³

More preferably 1～300: 700 × 10³；Most preferably 1～10: 700 × 10³

More preferably 1～300: 850 × 10³；Most preferably 1～10: 850 × 10³

When 2.4 hydroxy camptothecins and vitamin C palmityl ester share the medicine of preparation treatment people's gastric cancer,

1: 2～5000

Preferably 1: 5.5～2833

Or preferably 1～333: 1833～2833

More preferably 1～333: 550；Most preferably 1～10: 550

More preferably 1～333: 700；Most preferably 10～33: 700

More preferably 1～300: 850；Most preferably 1～100: 850

When 2.5 cisplatin and vitamin C palmityl ester share the medicine of preparation treatment people's gastric cancer,

The molar ratio of cisplatin and vitamin C palmityl ester may is that

1: 5～10000

Preferably 1: 18.3～8500

Or preferably 1～300: 5500～8500

More preferably 1～300: 5500；Most preferably 10～300: 5500

More preferably 1～300: 7000；Most preferably 3～300: 7000

More preferably 1～300: 8500；Most preferably 100～300: 8500

When 3.1 vincristine and vitamin C palmityl ester share the medicine of preparation treatment people's gastric cancer,

The molar ratio of vincristine and vitamin C palmityl ester may is that

1∶1×10³～1 × 10⁶

Preferably 1: 9 × 10³～480 × 10³

Or preferably 1～32: 288 × 10³～480 × 10³

More preferably 1～32: 288 × 10³；Most preferably 4～8: 288 × 10³

More preferably 1～32: 384 × 10³；Most preferably 2～32: 384 × 10³

More preferably 1～32: 480 × 10³；Most preferably 2～4: 480 × 10³

When 3.2 paclitaxels and vitamin C palmityl ester share the medicine of preparation treatment people's gastric cancer,

The molar ratio of paclitaxel and vitamin C palmityl ester may is that

1∶1×10³～1 × 10⁶

Preferably 1: 1.5 × 10³～750 × 10³

Or preferably 1～300: 450 × 10³～750 × 10³

More preferably 1～300: 450 × 10³；Most preferably 3～100: 450 × 10³

More preferably 1～300: 600 × 10³；Most preferably 3～30: 600 × 10³

More preferably 1～300: 750 × 10³；Most preferably 1～10: 750 × 10³

When 3.3 hydroxy camptothecins and vitamin C palmityl ester share the medicine of preparation treatment people's gastric cancer, hydroxy camptothecin and May is that with the molar ratio of vitamin C palmityl ester

1: 2～5000

Preferably 1: 5.5～2833

Or preferably 1～333: 1833～2833

More preferably 1～300: 4500；Most preferably 10～300: 4500

More preferably 1～300: 6000；Most preferably 10～100: 6000

More preferably 1～300: 7500；Most preferably 30～300: 7500

When 3.4 cisplatin and vitamin C palmityl ester share the medicine of preparation treatment people's gastric cancer,

The molar ratio of cisplatin and vitamin C palmityl ester may is that

1: 5～10000

Preferably 1: 15～7500

Or preferably 1～300: 4500～7500

More preferably 1～300: 4500；Most preferably 30～300: 4500

More preferably 1～300: 6000；Most preferably 1～3: 6000

More preferably 1～300: 7500；Most preferably 3～100: 7500

When 3.5 oxaliplatins and vitamin C palmityl ester share the medicine of preparation treatment people's gastric cancer,

The molar ratio of oxaliplatin and vitamin C palmityl ester may is that

1: 5～10000

Preferably 1: 15～7500

Or preferably 1～300: 4500～7500

More preferably 1～300: 4500；Most preferably 3～30: 4500

More preferably 1～300: 6000；Most preferably 3～300: 6000

More preferably 1～300: 7500；Most preferably 10～100: 7500

When 4.1 amycin and vitamin C palmityl ester share the medicine of preparation treatment human prostata cancer,

The molar ratio of amycin and vitamin C palmityl ester may is that

1∶1×10³～1 × 10⁶

Preferably 1: 1.5 × 10³～750 × 10³

Or preferably 1～300: 450 × 10³～750 × 10³

More preferably 1～300: 200 × 10³；Most preferably 1～10: 200 × 10³

More preferably 1～300: 225 × 10³；Most preferably 3～100: 225 × 10³

More preferably 1～300: 250 × 10³；Most preferably 3～300: 250 × 10³

When 4.2 vincristine and vitamin C palmityl ester share the medicine of preparation treatment human prostata cancer,

The molar ratio of vincristine and vitamin C palmityl ester may is that

1∶10×10³～1 × 10⁷

Preferably 1: 20 × 10³～8333 × 10³

Or preferably 1～333: 6667 × 10³～8333 × 10³

More preferably 1～333: 6667 × 10³；Most preferably 10-100: 6667 × 10³

More preferably 1～333: 7500 × 10³；Most preferably 1～100: 7500 × 10³

More preferably 1～333: 8333 × 10³；Most preferably 1～100: 8333 × 10³

When 4.3 hydroxy camptothecins and vitamin C palmityl ester share the medicine of preparation treatment human prostata cancer,

1: 2～5000

Preferably 1: 5.5～2833

Or preferably 1～333: 66667～83333

More preferably 1～333: 66667；Most preferably 1～10: 66667

More preferably 1～333: 75000；Most preferably 1～100: 75000

More preferably 1～333: 83333；Most preferably 1～10: 83333

4.4 cisplatin and and vitamin C palmityl ester share preparation treatment human prostata cancer medicine time,

The molar ratio of cisplatin and vitamin C palmityl ester may is that

1: 5～10000

Preferably 1: 15～7500

Or preferably 1～300: 4500～7500

More preferably 1～300: 20000；Most preferably 1～100: 20000

More preferably 1～300: 22500；Most preferably 10～100: 22500

More preferably 1～300: 25000；Most preferably 1～100: 25000

When 5.1 vincristine and vitamin C palmityl ester share the medicine of preparation treatment people's glioma,

The molar ratio of vincristine and vitamin C palmityl ester may is that

1: 500～160 × 10³

Preferably 1: 1 × 10³～80 × 10³

Or preferably 1～32: 40 × 10³～80 × 10³

More preferably 1～32: 40 × 10³；Most preferably 8～16: 40 × 10³

More preferably 1～32: 60 × 10³；Most preferably 16～32: 60 × 10³

More preferably 1～32: 80 × 10³；Most preferably 1～16: 80 × 10³

When 5.2 hydroxy camptothecins and vitamin C palmityl ester share the medicine of preparation treatment people's glioma,

1: 1～5000

Preferably 1: 2.5～2833

Or preferably 1～333: 833～1667

More preferably 1～333: 833；Most preferably 1～33: 833

More preferably 1～333: 1250；Most preferably 1～33: 1250

More preferably 1～333: 1667；Most preferably 10～33: 1667

When 5.3 cisplatin and vitamin C palmityl ester share the medicine of preparation treatment people's glioma,

The molar ratio of cisplatin and vitamin C palmityl ester may is that

1: 1～5000

Preferably 1: 2.5～2833

Or preferably 1～333: 833～1667

More preferably 1～333: 833；Most preferably 100～333: 833

More preferably 1～333: 1250；Most preferably 10～333: 1250

More preferably 1～333: 1667；Most preferably 10～333: 1667

When 5.4 temozolomides and vitamin C palmityl ester share the medicine of preparation treatment people's glioma,

The molar ratio of temozolomide and vitamin C palmityl ester may is that

1: 1～5000

Preferably 1: 2.5～2833

Or preferably 1～333: 833～1667

More preferably 1～32: 8；Most preferably 2～8: 8

More preferably 1～32: 12；Most preferably 8～32: 12

More preferably 1～32: 16；Most preferably 8～32: 16

When 6.1 amycin and vitamin C palmityl ester share the medicine of preparation treatment human breast carcinoma,

The molar ratio of amycin and vitamin C palmityl ester may is that

1: 100～100 × 10³

Preferably 1: 267～100 × 10³

Or preferably 1～300: 80 × 10³～100 × 10³

More preferably 1～300: 80 × 10³；Most preferably 3～300: 80 × 10³

More preferably 1～300: 90 × 10³；Most preferably 1～100: 90 × 10³

More preferably 1～300: 100 × 10³；Most preferably 1～100: 100 × 10³

When 6.2 vincristine and vitamin C palmityl ester share the medicine of preparation treatment human breast carcinoma,

The molar ratio of vincristine and vitamin C palmityl ester may is that

1∶1×10³～100 × 10⁴

Preferably 1: 4 × 10³～100 × 10³

Or preferably 1～32: 128 × 10³～160 × 10³

More preferably 1～32: 128 × 10³；Most preferably 3～32: 128 × 10³

More preferably 1～32: 140 × 10³；Most preferably 2～16: 140 × 10³

More preferably 1～32: 160 × 10³；Most preferably 1～16: 160 × 10³

When 6.3 paclitaxels and vitamin C palmityl ester share the medicine of preparation treatment human breast carcinoma,

The molar ratio of paclitaxel and vitamin C palmityl ester may is that

1∶1.0×10³～1000 × 10³

Preferably 1: 2.7 × 10³～1000 × 10³

Or preferably 1～300: 800 × 10³～1000 × 10³

More preferably 1～300: 800 × 10³；Most preferably 3～30: 800 × 10³

More preferably 1～300: 900 × 10³；Most preferably 1～10: 900 × 10³

More preferably 1～300: 1000 × 10³；Most preferably 1～10: 1000 × 10³

When 6.4 hydroxy camptothecins and vitamin C palmityl ester share the medicine of preparation treatment human breast carcinoma,

1: 2～5000

Preferably 1: 5.5～2833

Or preferably 1～333: 1833～2833

More preferably 1～300: 8000；Most preferably 1～100: 8000

More preferably 1～300: 9000；Most preferably 1～10: 9000

More preferably 1～300: 10000；Most preferably 1～10: 10000

The pharmaceutical composition facilitating the present invention in order to use can also comprise acceptable adjuvant on pharmaceutics.Described medicine The acceptable adjuvant of agent, including solvent, solubilizing agent, stabilizer, excipient, carrier, macromolecular material, surfactant, freezes Dry protective agents etc., are mainly selected from water for injection, normal saline, ethanol, propylene glycol, glycerol；Polyethylene glycol 200, Polyethylene Glycol 400, Macrogol 600, lithium 12-hydroxy stearate, polyoxyethylene castor oil class, polysorbate, tween, span, deoxidation gallbladder Barbiturates, cholate, poloxamer, polyvinylpyrrolidone, oiliness fatty acid and single or two glyceride thereof；Lactose, sucrose, wood Sugar alcohol, sorbitol, mannitol, lactose, dextran, d-xylose, glucose；Phospholipid, gelatin, arabic gum, Lac, melon ear Locust beam gum, agar, alginic acid and salt thereof, polyvinyl alcohol, Polyethylene Glycol, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyethylene Ketopyrrolidine, ethylene one acetate ethylene copolymer, polyamide, cellulose acetate, polyacrylic resin, ethyl cellulose, card ripple The acid of nurse, albumin, chitosan, glucosan, chitin, polylactic acid, polycaprolactone, polylactic-co-glycolic acid, polyvinyl alcohol, poly-hydroxyl Guanidine-acetic acid, phosphatidylcholine class, phosphatidyl glycerol class, phosphatidyl-4 alcohols, cytoskeletal protein, sphingomyelin class, list Chain or dichain phospholipids (two Semen Myristicae acid phosphatidyl glycerols, tin dilaurate phosphatidyl glycerol, two palmitic acid phosphatidyl glycerols, distearyl Acid phosphatidyl glycerol, two Semen Myristicae acid phosphatidic acid, tin dilaurate phosphatidic acid, two palmitic acid phosphatidic acid, distearyl acid phosphatidic acid, two oil Acid Phosphatidylserine, dilinoleic acid phosphatidylinositols, DPPC, tin dilaurate phosphatidylcholine, two meat Myristic acid phosphatidylcholine, distearoyl phosphatidylcholine, single Semen Myristicae acid phosphatidyl glycerol, mono laurate phosphatidyl glycerol, list Palmitic acid phosphatidyl glycerol, monostearate phosphatidyl glycerol, single Semen Myristicae acid phosphatidic acid, mono laurate phosphatidic acid, single palmitic acid phosphorus Fat acid, monostearate phosphatidic acid, single oleic acid Phosphatidylserine, single linoleic acid phosphatidylinositols, single Palmic acid phosphatidylcholine, Mono laurate phosphatidylcholine, single myristic acid phosphatidylcholine, MSPC, lecithin, soybean phospholipid, the heart One in phospholipid, naturally occurring or synthetic cephalin, cholesterol, two or more use simultaneously.

The dosage form of this law pharmaceutical composition is preferably prepared to injection preparation or oral formulations, including Injectable sterile subpackage The relevant controlled release forms such as powder, oil for injection, liposome, microemulsion, microsphere, nano particle preparations, oral lipid body, microemulsion, micro- The controlled release form that ball, nano particle preparations etc. are relevant.

Such as a example by Injectable liposomal, the preparation technology of this compound preparation is as follows:

Precision weighs the vitamin C palmityl ester of recipe quantity, chemotherapeutics, carrier are dissolved in organic solvent, and rotation subtracts Pressure evaporating organic solvent, obtains uniform lipid membrane, is placed in addition water for injection water after being dried overnight in vacuum drying oven Change, ultrasonic make film separation, process through probe sonication or high pressure homogenize, through membrane filtration granulate, to obtain final product.

The pharmaceutical composition of the present invention has good effect in antineoplastic is treated.Especially for malignant tumor, Described tumor is including but not limited to melanoma, gastric cancer, pulmonary carcinoma, breast carcinoma, renal carcinoma, hepatocarcinoma, oral cavity epidermal carcinoma, cervix uteri Cancer, ovarian cancer, cancer of pancreas, carcinoma of prostate, colon cancer, bladder cancer, cerebroma, the esophageal carcinoma, lymphoma, nervous system cancer etc. are swollen Tumor.Described cerebroma is particularly preferably from glioma.Especially for hepatocarcinoma, cancer of pancreas, glioma, the esophageal carcinoma, there is outstanding effect Really.

The invention provides the using method of medicine of the present invention, this vitamin C palmityl ester medicine is except for intratumor injection Outward, it may also be used for the modes such as vein, intra-arterial injection, oral, interventional therapy are administered.Interventional therapy and intratumor injection, be in recent years The treatment technology that new development is got up, drug injection directly can be entered tumor locus, allow medicament to directly act on by them In tumor tissues and tumor cell, there is extraordinary targeting, the general toxic and side effects of antitumor drug can be substantially reduced. The interventional therapy of various ways clinically, be generally acknowledge at present can not the malignant tumor of excision (especially middle and advanced stage is primary Property hepatocarcinoma or hepatic metastasis cancer) first-selected treatment means, commonly accept for numerous clinicians.Intratumor injection belongs to intervention The one for the treatment of, it is by special equipment by medicine, in direct injection to solid tumor mass, thus plays that to kill tumor thin The effect of born of the same parents.The tumor killing cell effect of large doses of vitamin C palmityl ester, is the most sufficiently confirmed in test in vitro, Therefore select the intervention of vitamin C palmityl ester or intratumor injection mode to be administered, it is possible to reach best anticancer effect.The medicine of the present invention Thing in addition to can be used for intravenous injection or intravenous drip, clinic be also preferentially used for the solid malignant such as hepatocarcinoma, cancer of pancreas and Intratumor injection, interventional therapy and the vein of its Several Kinds of Malignancy such as cerebroma, the esophageal carcinoma etc., tremulous pulse, muscle, the special way such as subcutaneous Footpath is administered, and is also used for, because the reason of body part cannot carry out, with operation, radiation etc., the solid tumor treated, being additionally operable to clinical need Want the tumor that comprehensive means is treated.

The invention also discloses a kind of medicine box, comprise any one medicine above-mentioned.

Advantageous Effects:

1) medicine of the present invention can strengthen the Chemotherapy of antitumor drug, even has synergism.

2) medicine of the present invention can reduce the toxic and side effects of antitumor drug, increases patient's tolerance agent for antitumor drug Amount.

3), compared with the medicine for the treatment of malignant tumor existing with market or Common Chemotherapy medicine, the present invention selects safety good Vitamin C palmityl ester as antineoplastic principal agent, have that antitumor spectra is wide, effect clearly, side effect is little, be not likely to produce drug resistance Property advantage, and this medicine may be used for intratumor injection be administered, drastically increase the therapeutic effect of solid malignant.

Fig. 1 .PA pharmacy in vitro experiment in MCF-7 cell.

Fig. 2 .PA pharmacy in vitro experiment in HepG-II cell.

Fig. 3 .PA pharmacy in vitro experiment in A549 cell.

Fig. 4 .PA pharmacy in vitro experiment in SGC-7901 cell.

Fig. 5 .PA pharmacy in vitro experiment in BxPC-3 cell.

Fig. 6 .PA pharmacy in vitro experiment in Hela cell.

Fig. 7 .PA pharmacy in vitro experiment in U251 cell.

Fig. 8 .PA pharmacy in vitro experiment in PC-3 cell.

Fig. 9 .PA pharmacy in vitro experiment in LOVO cell.

Figure 10 .PA pharmacy in vitro experiment in HELF cell.

Figure 11-1.PA pharmacy in vitro experiment in U87 cell.

Figure 11-2.PA pharmacy in vitro experiment in HCT-116 cell.

Figure 11-3.PA pharmacy in vitro experiment in HCT-116 cell.

Pharmacy in vitro after Figure 12-1. amycin acts solely on MCF-7 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 12-2. paclitaxel acts solely on MCF-7 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 12-3. Docetaxel acts solely on MCF-7 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 12-4. vincristine acts solely on MCF-7 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 12-5. hydroxy camptothecin acts solely on MCF-7 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-1. amycin acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-2. paclitaxel acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-3. Docetaxel acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-4. vincristine acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-5. hydroxy camptothecin acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-6. oxaliplatin acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-7. cisplatin acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-8. carboplatin acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-9. gemcitabine acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 13-10. Sorafenib acts solely on HepG-II and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 14-1. amycin acts solely on A549 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 14-2. paclitaxel acts solely on A549 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 14-3. Docetaxel acts solely on A549 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 14-4. vincristine acts solely on A549 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 14-5. hydroxy camptothecin acts solely on A549 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 14-6. gemcitabine acts solely on A549 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 15-1. amycin acts solely on SGC-7901 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 15-2. paclitaxel acts solely on SGC-7901 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 15-3. Docetaxel acts solely on SGC-7901 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 15-4. vincristine acts solely on SGC-7901 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 15-5. hydroxy camptothecin acts solely on SGC-7901 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 15-6. oxaliplatin acts solely on SGC-7901 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 16-1. amycin acts solely on BxPC-3 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 16-2. paclitaxel acts solely on BxPC-3 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 16-3. Docetaxel acts solely on BxPC-3 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 16-4. vincristine acts solely on BxPC-3 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 16-5. hydroxy camptothecin acts solely on BxPC-3 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 16-6. gemcitabine acts solely on BxPC-3 and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 17-1. amycin acts solely on Hela and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 17-2. paclitaxel acts solely on Hela and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 17-3. Docetaxel acts solely on Hela and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 17-4. vincristine acts solely on Hela and share with variable concentrations PA is tested.

Pharmacy in vitro after Figure 17-5. hydroxy camptothecin acts solely on Hela and share with variable concentrations PA is tested.

Figure 18. vitamin C palmityl ester solution (PA) and vitamin c solution (VC) are real at pharmacy in vitro intracellular for A549 Test.

Figure 19. tumor-bearing mice gives normal saline (Saline), amycin aqueous solution (DOX solution, 0.1mg/kg), PA After nanoparticle (PA-NPS, 20mg/kg), compound recipe nanoparticle (DOX-PA-NPS, DOX:0.1mg/kg, PA:20mg/kg), each group Tumor size change.

Figure 20. tumor-bearing mice gives normal saline (Saline), amycin aqueous solution (DOX solution, 0.1mg/kg), PA After nanoparticle (PA-NPS, 20mg/kg), compound recipe nanoparticle (DOX-PA-NPS, DOX:0.1mg/kg, PA:20mg/kg), each group Body weight change.

Detailed description of the invention

Below in conjunction with detailed description of the invention, the invention will be further described, this part not limitation of the invention, depends on According to prior art well known in the art, embodiments of the present invention are not limited to this, the most all according to disclosure of invention institute The equivalent of this area made, belongs to protection scope of the present invention.

Embodiment 1: injection vitamin C palmityl ester liposome

Weighing vitamin C palmityl ester, soybean phospholipid and the cholesterol of recipe quantity, be dissolved in dichloromethane, juxtaposition rotation is steamed Drying under reduced pressure in instrument, makes into a uniform lipid membrane, is placed in after being dried overnight in vacuum drying oven, adds water for injection water Change, ultrasonic make film separation, process through probe sonication or high pressure homogenize, after through 0.22 μm filtering with microporous membrane granulate, Obtain.

Embodiment 2: injection use compound liposome

Weigh vitamin C palmityl ester, Docetaxel, phospholipid and the cholesterol of recipe quantity, be dissolved in dichloromethane, and Put rotation and steam drying under reduced pressure in instrument, make into a uniform lipid membrane, be placed in after vacuum drying oven is dried overnight, add injection Water hydratable, ultrasonic makes film separation, processes through probe sonication or high pressure homogenize, after whole through 0.22 μm filtering with microporous membrane Grain, to obtain final product.

Embodiment 3: injection vitamin C palmityl ester nanoparticles

PLGA is dissolved in acetone formation PLGA acetone soln, by vitamin C palmityl ester, adds PLGA acetone soln Middle as oil phase, soybean phospholipid is dissolved in ethanol solution, adds poloxamer, DSPE-PEG-BIOTIN, water-bath removes organic molten Oil phase as aqueous phase, is added dropwise in the aqueous phase of constant temperature stirring by agent, drips complete follow-up continuous stirring to remove organic solvent, by it Add in bag filter after dialysed overnight, add mannitol lyophilization, to obtain final product.

Embodiment 4: injection use compound nanoparticle

PLGA is dissolved in acetone formation PLGA acetone soln, vitamin C palmityl ester, amycin are added PLGA third As oil phase in ketone solution, soybean phospholipid being dissolved in ethanol solution, add poloxamer, DSPE-PEG-BIOTIN, water-bath removes Oil phase, as aqueous phase, is added dropwise in the aqueous phase of constant temperature stirring by organic solvent, drips complete follow-up continuous stirring organic molten to remove Agent, is added in bag filter after dialysed overnight, adds mannitol lyophilization, to obtain final product.

Pharmacological evaluation:

Experimental example 1, the pharmacy in vitro experiment of vitamin C palmityl ester

Medicine is prepared

Weigh vitamin C palmityl ester to be dissolved in autoclaving water, make 1mol/L storing solution, in superclean bench with 0.22 μm disposable pin type filter filters, and is stored in-80 DEG C of refrigerators, and the used time is directly added in culture fluid the medicine being made into respective concentration Liquid.

Mtt assay measures cytoactive

The take the logarithm cell strain of trophophase, after 0.25% trypsinization, is cultivated with the RPMI1640 containing 10% hyclone Liquid is made into single cell suspension, with 3 × 10³The density of individual/mL is inoculated in 96 orifice plates, and every hole adds 100 μ L cell suspension, is placed in 37 DEG C, 5%CO₂Incubator is cultivated in aseptic culture case 24h, after cell is the most adherent, removes original culture fluid, every hole The variable concentrations vitamin C palmityl ester 100 μ L that addition configures with culture fluid.Matched group adds the culture fluid containing 0.1%DMSO, Cultivate 72h for 37 DEG C.Cultivation is inhaled after terminating and is abandoned medicinal liquid, and every hole adds PBS 100 μ L and washes away the medicinal liquid of residual, and every hole adds containing 10% 5mg/mL MTT working solution culture fluid 100 μ L, 37 DEG C are continued to cultivate 4h.Supernatant is abandoned in suction, and every hole adds 150 μ L DMSO, shakes Swing 10min with abundant dissolving crystallized thing, under microplate reader 570nm, measure OD value, give tumor after medicine by following equation calculating The survival rate of cell, and use GraphPad data processing software calculation of half inhibitory concentration (IC₅₀)。

Above-mentioned cell strain is selected from: MCF-7 cell strainHJ2mm, human hepatoma cell strain HepG-II, human lung carcinoma cell line A549, human stomach cancer cell line SGC-7901, MKN45, people in situ pancreas cancer cell strain BxPC-3, human cervical carcinoma cell lines Hela, Human glioma cells strain U251, human prostate cancer cell line PC-3, human colon cancer cell strain LOVO, human embryonic lung fibroblast strain HELF, human glioma cell U-87, Human colorectal cancer cells strain HCT-116.

Experimental result: see accompanying drawing 1～11 and table 1.

Experimental result shows, the vitamin C palmityl ester IC to different tumor cell lines₅₀It is respectively less than 200 μMs, anticancer effect Stronger.

Table 1-1: the vitamin C palmityl ester (hereinafter referred to as PA) suppression ratio in different cell strains

Table 1-2.PA IC in different cell strains₅₀Value

Experimental example 2, vitamin C palmityl ester and various chemotherapeutic share the effect to tumor cell

Medicine is prepared

Mtt assay measures activity of tumor cells

The take the logarithm cell strain of trophophase, after 0.25% trypsinization, is cultivated with the RPMI1640 containing 10% hyclone Liquid is made into single cell suspension, with 3 × 10³The density of individual/mL is inoculated in 96 orifice plates, and every hole adds 100 μ L cell suspension, is placed in 37 DEG C, 5%CO₂Incubator is cultivated in aseptic culture case 24h, after cell is the most adherent, removes original culture fluid, every hole The antineoplastic drug solution 50 μ L of the variable concentrations that addition is prepared with culture fluid, adds by the variable concentrations dimension of culture fluid configuration Raw element C palmityl ester 50 μ L.Matched group adds the culture fluid containing 0.1%DMSO, cultivates 72h for 37 DEG C.Cultivation is inhaled after terminating and is abandoned medicine Liquid, every hole adds PBS 100 μ L and washes away the medicinal liquid of residual, and every hole adds the MTT working solution culture fluid 100 μ L Han 10%5mg/mL, 37 DEG C are continued to cultivate 4h.Supernatant is abandoned in suction, and every hole adds 150 μ L DMSO, and 10min is with abundant dissolving crystallized thing, at enzyme mark in vibration Measure OD value under instrument 570nm, calculate by following equation and give the suppression ratio of tumor cell after medicine, at employing GraphPad data Reason computed in software half-inhibition concentration (IC₅₀), and according to IC₅₀Calculate the vitamin C palmityl ester of chemotherapeutics and variable concentrations Share rear IC₅₀Reduce multiple.

Vitamin C palmityl ester improves the determination methods of the Chemotherapy of medicine A

IR (A+PA) ＞ IR (A), represents that the existence of vitamin C palmityl ester improves the Chemotherapy of medicine A, the upper right corner It is labeled as^▲。

Synergism determination methods

By following computational methods, synergism is judged:

, between medicine, there is synergism in IR (A+B) ＞ IR (A)+IR (B)-IR (A) × IR (B)；

IR (A+B)=IR (A)+IR (B)-IR (A) × IR (B), simply simple superposition effect between medicine；

, between medicine, there is antagonism in IR (A+B) ＜ IR (A)+IR (B)-IR (A) × IR (B)；

Wherein IR (A+B), IR (A), IR (B) the most corresponding medicine AB combination, life when A independent role and B independent role Long suppression ratio.

The result of IR (A)+IR (B)-IR (A) × IR (B) is shown as predictive value, and as associated with AB, suppression ratio { IR (A+B) } is big In predictive value, then it represents that share and there is synergism.Prime marks^▲▲For having synergism.If suppression ratio is negative value person's note It is 0.

Above-mentioned cell strain is selected from: MCF-7 cell strainHJ2mm, human hepatoma cell strain HepG-II, human lung carcinoma cell line A549, human stomach cancer cell line SGC-7901, people pancreas adenocarcinoma cell strain BxPC-3, human cervical carcinoma cell lines Hela in situ.

Experimental result: see accompanying drawing and table 2～46.

Table 2-A-I: vitamin C palmityl ester (hereinafter referred to as PA) share amycin 72h to MCF-7 cell strainHJ2mm Exercising result

Note: "^▲▲" represent that there is synergism；“^▲" represent that PA can improve chemotherapeutic effect

Table 3-B-I:PA share the paclitaxel 72h exercising result to MCF-7 cell strainHJ2mm

Table 4-C-I:PA share the Docetaxel 72h exercising result to MCF-7 cell strainHJ2mm

Table 5-D-I:PA share the vincristine 72h exercising result to MCF-7 cell strainHJ2mm

Table 6-F-I PA share the hydroxy camptothecin 72h exercising result to MCF-7 cell strainHJ2mm

Table 7: chemotherapeutics acts solely on human breast cancer cell line Bcap-37 and share rear chemotherapeutics with variable concentrations PA IC₅₀And drug effect increases multiple

Table 8:PA share the amycin 72h exercising result to human hepatoma cell strain HepG-II

Table 9-B-II:PA share paclitaxel to the 72h exercising result to human hepatoma cell strain HepG-II

Table 10-C-II:PA share Docetaxel to the 72h exercising result to human hepatoma cell strain HepG-II

Table 11-D-II:PA share vincristine to the 72h exercising result to human hepatoma cell strain HepG-II

Table 12-F-II:PA share the hydroxy camptothecin 72h exercising result to human hepatoma cell strain HepG-II

Table 13-I-II:PA share the oxaliplatin 72h exercising result to human hepatoma cell strain HepG-II

Table 14-G-II:PA share the cisplatin 72h exercising result to human hepatoma cell strain HepG-II

Table 15-H-II:PA share the carboplatin 72h exercising result to human hepatoma cell strain HepG-II

Table 17-E-II:PA share gemcitabine to the 72h exercising result to human hepatoma cell strain HepG-II

Table 18-K-II:PA share Sorafenib to the 72h exercising result to human hepatoma cell strain HepG-II

Table 19: chemotherapeutics acts solely on human liver cancer cell HepG-II and share rear chemotherapeutics with variable concentrations PA IC₅₀And drug effect increases multiple

“^▲" represent that PA can improve chemotherapeutic effect

Table 20-A-III:PA share amycin to the 72h exercising result to human lung carcinoma cell line A549

Table 21-B-III:PA share paclitaxel to the 72h exercising result to human lung carcinoma cell line A549

Table 22-C-III:PA share Docetaxel to the 72h exercising result to human lung carcinoma cell line A549

Table 23-D-III:PA share vincristine to the 72h exercising result to human lung carcinoma cell line A549

Table 24-F-III:PA share hydroxy camptothecin to the 72h exercising result to human lung carcinoma cell line A549.

Table 25-E-III:PA share the gemcitabine 72h exercising result to human lung carcinoma cell line A549

Table 26: chemotherapeutics acts solely on human lung cancer cell A549 and share rear chemotherapeutics with variable concentrations PA IC₅₀And drug effect increases multiple

Table 27-A-IV:PA share the amycin 72h exercising result to human stomach cancer cell line SGC-7901

Table 28-B-IV:PA share the paclitaxel 72h exercising result to human stomach cancer cell line SGC-7901

Table 29-C-IV:PA share the Docetaxel 72h exercising result to human stomach cancer cell line SGC-7901.

Table 30-D-IV:PA share the vincristine 72h exercising result to human stomach cancer cell line SGC-7901

Table 31-F-IV:PA share the hydroxy camptothecin 72h exercising result to human stomach cancer cell line SGC-7901

Table 32-I-IV:PA share the oxaliplatin 72h exercising result to human stomach cancer cell line SGC-7901

Table 33: chemotherapeutics acts solely on SGC-7901 cells and share rear chemotherapeutics with variable concentrations PA IC₅₀And drug effect increases multiple

Table 34-A-V:PA share the amycin 72h exercising result to human pancreas cancer cell strain BxPC-3

Table 35-B-V:PA share the paclitaxel 72h exercising result to human pancreas cancer cell strain BxPC-3.

Table 36-C-V:PA share the Docetaxel 72h exercising result to human pancreas cancer cell strain BxPC-3

Table 37-D-V:PA share vincristine to the 72h exercising result to human pancreas cancer cell strain BxPC-3.

Table 38-F-V:PA share the hydroxy camptothecin 72h exercising result to human pancreas cancer cell strain BxPC-3

Table 39-E-V:PA share gemcitabine to the 72h exercising result to human pancreas cancer cell strain BxPC-3.

Table 40: chemotherapeutics acts solely on human pancreas cancer BxPC-3 and share rear chemotherapeutics with variable concentrations PA IC₅₀And drug effect increases multiple

Table 41-A-VI:PA share the amycin 72h exercising result to human cervical carcinoma cell lines Hela

Table 42-B-VI:PA share paclitaxel to the 72h exercising result to human cervical carcinoma cell lines Hela

Table 43-C-VI:PA share Docetaxel to the 72h exercising result to human cervical carcinoma cell lines Hela

Table 44-D-VI:PA share vincristine to the 72h exercising result to human cervical carcinoma cell lines Hela.

Table 45-F-VI:PA share the hydroxy camptothecin 72h exercising result to human cervical carcinoma cell lines Hela

Table 46: chemotherapeutics acts solely on human cervical carcinoma cell Hela and share rear chemotherapeutics with variable concentrations PA IC₅₀And drug effect increases multiple

Experimental example 1: vitamin C palmityl ester compares human breast cancer cell A549 with the experiment of vitamin C pharmacy in vitro

Medicine is prepared

Weigh vitamin C palmityl ester, vitamin C is dissolved in autoclaving water, makes 1mol/L storing solution, in ultra-clean work Filtering with 0.22 μm disposable pin type filter in station, be stored in-80 DEG C of refrigerators, the used time is directly added in culture fluid and is made into accordingly The medicinal liquid of concentration.

Mtt assay measures cytoactive

Select the attached tumor cells (human breast cancer cell, A549) of exponential phase, after trypsinization, with containing 10% 1640 culture medium of calf serum are made into 2.5*10⁴The cell suspension of individual/mL, is seeded in 96 well culture plates, every hole inoculation 200 μ L, 37 DEG C, 5%CO2 cultivates 24h.

Add the most celliferous culture medium during blank group bed board, during dosing, add the culture medium of not pastille；What experimental group renewed contains The culture medium of variable concentrations sample, matched group then changes the culture medium containing equal-volume solvent, and often group sets 6 parallel holes, 37 DEG C, 5%CO2 cultivates 72h.Experiment component is vitamin c solution group, vitamin C palmityl ester solution group, vitamin c solution group 0.128～10000 μM, vitamin C palmityl ester solution group: 0.003456～270 μM.Abandoning supernatant, with PBS 2～3 Secondary, every hole adds the 200 freshly prepared serum-free mediums containing 0.5mg/mL MTT of μ L, and 37 DEG C are continued to cultivate 4h.Carefully abandon Supernatant, and add 150 μ L DMSO, after mixing with miniature ultrasonic agitator, microplate reader measures OD value with wavelength for 490nm, Use GraphPad data processing software calculation of half inhibitory concentration (IC₅₀)。

Experimental result: see accompanying drawing 18

Experimental result shows, compared with vitamin c solution group, and the IC of vitamin C palmityl ester solution group₅₀Value substantially fall Low.

Table 2: vitamin C palmityl ester (PA) and the vitamin c solution (VC) suppression ratio in human lung cancer cell A549

Table 2. vitamin C palmityl ester solution (PA) and the vitamin c solution (VC) IC in human lung cancer cell A549₅₀Value

Experiment 3: tumor-bearing mice anti-tumor in vivo is tested

Take certain density amycin and vitamin C palmityl ester compound recipe nanometer formulation, vitamin C palmityl ester nanometer system Agent, carries out tumor-bearing mice anti-tumor in vivo test with doxorubicin injection contrast.Using normal saline as negative control.

The foundation of animal model

Kunming kind male ICR white mice, aseptic aspiration third time is used to pass on the ascites of the mice of the 8th day, use serum-free RPMI1640 culture medium dilutes, and adjusts cell concentration to 1 × 10⁷Individual/mL, after rapid for mice etherization, skin of back is sterilized, Every mouse inoculation about 0.2mLHeps tumor cell suspension is in dorsal sc, and whole seeded process completed in 2 hours.

Experimental program

Use tail vein injection administering mode, normal saline group (Normal Saline), compound recipe amycin/vitamin C palm fibre Palmitic acid acyl ester nanoparticles group (amycin 0.1mg/kg, vitamin C palmityl ester 20mg/kg), vitamin C palmityl ester nanoparticles group (vitamin C palmityl ester 20mg/kg), Doxorubicin solution group (amycin 0.1mg/kg).At the 1st day, the 4th day, within the 7th day, respectively give Medicine once, measures the size of mouse tumor and Mouse Weight for every three days, and observes and the health of record mice and dead feelings Condition.

Experimental result is shown in accompanying drawing 19～20.

Experimental result shows, compared with normal saline group, compound recipe nanoparticle group, vitamin C palmityl ester nanoparticles group, Ah Mycin aqueous solution group all can produce drug effect, and wherein the drug effect of compound recipe nanoparticle is the strongest, secondly vitamin C palmityl ester nanoparticles group Drug effect be better than amycin aqueous solution group, illustrate that nano particle preparations exists advantage；After administration, the body weight of each group tumor-bearing mice becomes Change is not it is obvious that explanation compound recipe nanoparticle toxicity is less.

Claims

1. a medicine, it is characterised in that: active component is selected from vitamin C palmityl ester and at least one anti-tumor chemotherapeutic medicine Thing.

Medicine the most according to claim 1, it is characterised in that: described antineoplastic chemotherapy medicine is selected from antibiotics antitumor Medicine, anti-tumor botanical, anti-metabolism antineoplastic agent, platinum antineoplastic medicine, hormones antineoplastic agent, alkanisation class antineoplastic agent, Biological immune class antineoplastic agent, cell-differentiation inducers, monoclonal antibody, tyrosinase inhibitor, described m-TOR suppress Agent, immunosuppressant.

Medicine the most according to claim 2, it is characterised in that:

Described antibiotics antineoplastic agent is selected from amycin, mitomycin, daunorubicin, actinomycin D, Bleomycin A5, wins Bleomycin, doxorubicin, pirarubicin, epirubicin；

Described anti-tumor botanical is selected from vincristine, vincaleucoblastine, vinorelbine, vindesine, paclitaxel, Taxotere Alcohol, etoposide, Meisoindigotin；

Described anti-metabolism antineoplastic agent replaces selected from fluorouracil, methotrexate, cytosine arabinoside, capecitabine, tegafur, gimeracil and oteracil potassium, thunder Qu Sai, gemcitabine, pemetrexed, hydroxyurea, 6-MP, thioguanine, camptothecin analogues, ftorafur, fluorine urea Glycosides；

Described platinum antineoplastic medicine selected from cisplatin, carboplatin, oxaliplatin, nedaplatin, Lobaplatin,；

Described hormones antineoplastic agent is selected from dexamethasone, hydrocortisone, his rice former times sweet smell, toremifene, exemestane, ammonia Rumi spy, letrozole, fulvestrant, Anastrozole, flutamide, bicalutamide, progestogens, estrogens, androgen, rush Huang Body generates hormone-releasing hormone；

Described alkanisation class antineoplastic agent wishes miaow selected from cyclophosphamide, ifosfamide, Chlorambucil, chlormethine, chlorambucil, nitrogen Amine, carmustine, temozolomide, busulfan, phosphinothioylidynetrisaziridine, dacarbazine；

Described biological immune class antineoplastic agent selected from interferon, tumor necrosis factor, Thymic, interleukin,

Described cell-differentiation inducers is selected from retinoid, arsenious acid；

Described monoclonal antibody drug is selected from Herceptin, Rituximab, Cetuximab, bevacizumab, handkerchief torr pearl Monoclonal antibody.

Described tyrosinase inhibitor replaces Buddhist nun, La Pa selected from imatinib, gefitinib, erlotinib, Ai Ke for Buddhist nun, gram azoles For Buddhist nun, Sorafenib, Sutent, Ah handkerchief for Buddhist nun；

Described m-TOR inhibitor is selected from Yi Weimosi；

Described antineoplastic chemotherapy medicine is further selected from fludarabine, homoharringtonine, asparaginase, bortezomib.

Medicine the most according to claim 3, it is characterised in that:

Its derivant of described camptothecine is selected from hydroxy camptothecin, irinotecan, topotecan, etoposide, teniposide.

Described progestogens medicine is selected from medroxyprogesterone, megestrol；

Described estrogens medicine is selected from estrogen, diethylstilbestrol；

Described androgen medicine is selected from testosterone propionate；

Described luteinizing hormone-releasing hormone medicine is selected from goserelin, leuprorelin.

Described Thymic is selected from thymosin, Thymopentin, thymosin-alpha.

Medicine the most as claimed in one of claims 1-4, it is characterised in that: described compositions also comprises and can connect on pharmaceutics The adjuvant being subject to.

Medicine the most according to claim 5, it is characterised in that: on described pharmaceutics, acceptable adjuvant is selected from water for injection, life Reason saline, ethanol, propylene glycol, glycerol, polyethylene glycol 200, PEG400, Macrogol 600, lithium 12-hydroxy stearate, Polyoxyethylene castor oil class, polysorbate, tween, span, deoxycholic acid salt, cholate, poloxamer, polyvinyl pyrrole Alkanone, oiliness fatty acid and single or two glyceride thereof；Lactose, sucrose, xylitol, sorbitol, mannitol, lactose, dextrose Glycosides, d-xylose, glucose；Phospholipid, gelatin, arabic gum, Lac, guar gum, agar, alginic acid and salt thereof, polyvinyl alcohol, Polyethylene Glycol, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, ethylene one acetate ethylene copolymer, poly- Amide, cellulose acetate, polyacrylic resin, ethyl cellulose, carbomer, albumin, chitosan, glucosan, chitin, poly- The acid of lactic acid, polycaprolactone, polylactic-co-glycolic acid, polyvinyl alcohol, polyglycolic acid, phosphatidylcholine class, phosphatidyl glycerol class, Phosphatidyl-4 alcohols, cytoskeletal protein, sphingomyelin class, strand or dichain phospholipids (two Semen Myristicae acid phosphatidyl glycerols, two Lauric acid phosphatidyl glycerol, two palmitic acid phosphatidyl glycerols, DSPG, two Semen Myristicae acid phosphatidic acid, two Laurels Acid phosphatidic acid, two palmitic acid phosphatidic acid, distearyl acid phosphatidic acid, two oleic acid Phosphatidylserine, dilinoleic acid phosphatidylinositols, DPPC, tin dilaurate phosphatidylcholine, two myristic acid phosphatidylcholines, distearoylphosphatidyl gallbladder Alkali, single Semen Myristicae acid phosphatidyl glycerol, mono laurate phosphatidyl glycerol, single palmitic acid phosphatidyl glycerol, monostearate phosphatidyl are sweet Semen Myristicae acid phosphatidic acid oily, single, mono laurate phosphatidic acid, single palmitic acid phosphatidic acid, monostearate phosphatidic acid, single oleic acid phosphatidyl silk Propylhomoserin, single linoleic acid phosphatidylinositols, single Palmic acid phosphatidylcholine, mono laurate phosphatidylcholine, single myristic acid phospholipid Phatidylcholine, MSPC, lecithin, soybean phospholipid, cuorin, naturally occurring or synthetic cephalin, cholesterol.

Medicine the most according to claim 6, it is characterised in that: the dosage form of described medicine is selected from injection or oral formulations.

Medicine the most according to claim 7, it is characterised in that: injection or oral formulations are selected from various available nanoparticles, lipid Body and sustained-release preparation；Injection preparation is further selected from various available injection solution agent, injectable powder, oil for injection preparation.

9. the medicine of any one of claim 1-8 application in preparing antitumor drug.

Application the most according to claim 9, it is characterised in that: described tumor is selected from melanoma, gastric cancer, pulmonary carcinoma, mammary gland Cancer, renal carcinoma, hepatocarcinoma, G. cephalantha, cervical cancer, ovarian cancer, cancer of pancreas, carcinoma of prostate, colon cancer, bladder cancer, cerebroma, esophagus Cancer.

11. application according to claim 10, it is characterised in that: described tumor is selected from hepatocarcinoma, cancer of pancreas, glioma, esophagus Cancer.

12. 1 kinds of medicine boxs, it is characterised in that comprise any one medicine in claim 1-8.