CN100420442C - Pharmaceutical composition of scutellarin and baicalin with synergistic tumor resistance function - Google Patents

Abstract

The present invention relates to a medicine composition containing with wild baicalein and wild baicalin or baicalin, which has cooperative antineoplastic action. The present invention also relates to a preparing method of the compound and an application of the compound in preparing medicine.

Description

The wild-scutellaglucone of synergistic antitumor and baicalin pharmaceutical composition

Technical field

The present invention relates to a kind of pharmaceutical composition, be specifically related to a kind of pharmaceutical composition that contains flavone compound with synergistic antitumor effect with synergistic antitumor effect.The invention still further relates to the preparation method and the pharmaceutical applications of said composition.

Background technology

Chemotherapy is the abbreviation of " chemotherapy ".The notion of chemotherapy generally is understood that " chemotherapy of tumor " at present, promptly uses the antitumor chemicals, adopts the method for some measure and scheme treatment tumor.Yet common chemotherapeutics such as vincristine, cisplatin, methotrexate, cyclophosphamide, 5-fluorouracil (5-Fu) etc. can produce toxic and side effects such as injection site pain, venous thrombosis, bone marrow depression, gastrointestinal reaction, peripheral nervous pathological changes.

For the toxic and side effects that reduces chemotherapeutics, improve curative effect, reduce tumor recurrence and avoid drug-fast generation, selects different chemotherapy drugs in combination uses, become one of important means of chemotherapy of tumors.For example, clinically cisplatin and 5-Fu, bleomycin or epipodophyllotoxin etc. are united the use treatment esophageal carcinoma.

The curative effect sum of the curative effect that " synergism " (Synergistic Effect) produced when being meant two kinds of medication combined use when two prescriptions solely use during greater than same dose.According to middle effect principle (Joseph R.Bertino, Ting-Chao Chou, Chemotherapy:Synergism and Antagonism, Encyclopedia of Cancer, 1996, Academic Press, Inc.), two medicines unite action effect when using can pass through " association index " (Combination Index, CI) judge:

$\mathrm{CI}=\frac{D1}{\left(\mathrm{Dx}\right)1}+\frac{D2}{\left(\mathrm{Dx}\right)2}+\mathrm{\α}\×\frac{D1\×D2}{\left(\mathrm{Dx}\right)1\×\left(\mathrm{Dx}\right)2}$

Wherein, D1, D2 are respectively medicine 1 and medicine 2 when using separately, the drug level when cell proliferation inhibition rate reaches x%, (Dx) 1, the concentration of (Dx) 2 mixture Chinese medicine 1 and medicine 2 when reaching the same cell proliferation inhibition rate.

To two kinds of separate medicine α=0; And medicine α=1 independently not mutually.

When CI＜1, be synergism, during CI=1, be summation action; CI＞1 o'clock is antagonism.

The animal test model that the antitumorigenic substance of establishing in nineteen eighty-three according to national cancer institute screens, be used for having of the interior transplanted tumor strain of mice body: mouse melanin glucagonoma cell strain B16, solid tumor (entity tumor) tumor strains such as mice fibrosarcoma cell strain M5076; Blood such as mouse leukemia cell strain L1210 are the strain of tumor tumor. those of ordinary skill in the art to adopt and select for use certain tumor tumor strain to be used as animal vivo test model at transplantation tumor: as select for use the mice animal experiment of mouse melanin glucagonoma cell strain B16 to be used as animal vivo test model at entity tumor, heavy or tumor volume suppression ratio is as observation index with tumor; Selecting for use the mice animal experiment of mouse leukemia cell strain L1210 to be used as at blood is the animal vivo test model of tumor, with the increase in life span of tumor animal as observation index. the inside and outside result of the test of coalition judges whether test substance has antitumor action.

Wild-scutellaglucone, scutellarin and baicalin all belong to flavone compound, can extract to obtain from plants such as Herba Scutellariae Barbatae, Radix Scutellariae. and wherein the wild-scutellaglucone molecular weight is 286, molecular formula C ₁₅H ₁₀O ₆, structural formula is as follows:

The molecular weight of scutellarin is 463, molecular formula C ₂₁H ₁₉O ₁₂, structural formula is:

R wherein ₁Represent the glucal acidic group, R ₂Representation hydroxy. work as R ₂When representing hydrogen, above-claimed cpd is a baicalin, and its molecular weight is 446, molecular formula C ₂₁H ₁₈O ₁₁.

Do not see that so far relevant wild-scutellaglucone and scutellarin or baicalin have synergistic report on antitumor.

Summary of the invention

Appearance part of the present invention is based on such discovery: wild-scutellaglucone has synergism to scutellarin or baicalin, can obviously improve its killing activity to tumor cell; The pharmaceutical composition that contains wild-scutellaglucone and scutellarin and/or baicalin has enhanced antitumor action, and more effective than the pharmaceutical composition that only contains single wild-scutellaglucone, scutellarin or baicalin.

Therefore, one aspect of the present invention relates to wild-scutellaglucone and in preparation following general formula (I) chemical compound is had purposes in the synergistic antitumor drug:

Wherein, R ₁Represent the glucal acidic group, R ₂Represent hydrogen or hydroxyl.

Another aspect of the present invention relates to have the pharmaceutical composition of synergistic antitumor effect, and said composition comprises wild-scutellaglucone and general formula (I) chemical compound, the molar concentration rate of wherein said wild-scutellaglucone and general formula (I) chemical compound be 2: 1 to 1: 4.

The invention still further relates to the method and the purposes of aforementioned pharmaceutical compositions in the preparation antitumor drug that prepare aforementioned pharmaceutical compositions.

The specific embodiment of the present invention will set forth with the lower part. and other characteristics of the present invention, purpose and advantage will be shown by following elaboration.

The specific embodiment:

The inventor discovers, when wild-scutellaglucone of the present invention and scutellarin or baicalin administration simultaneously, can obviously improve its anti-tumor activity, thereby have synergism. can reduce its consumption, reduce its toxic and side effects. therefore, wild-scutellaglucone of the present invention and scutellarin or baicalin can be used for preparing the medicine of anti-tumor synergetic effect.

Wild-scutellaglucone of the present invention, scutellarin or baicalin are that nature exists and can be from certain plants such as Herba Scutellariae Barbataes, separate in the Radix Scutellariae and obtain. wild-scutellaglucone of the present invention, scutellarin or baicalin also can obtain or pass through the common synthetic technology of this area by commercial sources, microbial technique and animal and plant cells are synthetic to be made. be used for separating or synthetic wild-scutellaglucone of the present invention, the chemicals of scutellarin or baicalin comprises solvent, reagent, catalyst, blocking group reagent, remove blocking group reagent. described separation can also comprise adding or remove suitable blocking group finally to obtain required wild-scutellaglucone with synthetic, the step of scutellarin or baicalin. be used to prepare wild-scutellaglucone of the present invention, the synthetic chemistry of scutellarin or baicalin transforms and the method for radical protection (going protection) is known to those skilled in the art, can be referring to R.Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T.W.Greenand P.G.M.Wuts, Protective Groups in Organic Synthesis, 3 ^RdEd., John Wiley and Sons (1999), L.Fieser and M.Fieser, Fieser and Fieser ' s Reagents for Organic Synthesis, John Wiley andSons (1994); And L.Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wileyand Sons (1995) and follow-up works thereof.

Wild-scutellaglucone of the present invention can with administration simultaneously of scutellarin or baicalin or non-while administration; Can pass through intestinal or parenteral route administration.The intestinal canal administration preparation includes but not limited to capsule, tablet, Emulsion, aqueous suspension agent, colloidal solution, solution, microcapsule, pill, lozenge, granule, powder.The pharmaceutically suitable carrier that is usually used in tablet comprises lactose and corn starch.Usually also can add lubricants such as magnesium stearate.The pharmaceutically suitable carrier that is usually used in capsule comprises lactose and dried corn starch.When making oral aqueous suspension agent and/or Emulsion, pharmaceutical composition of the present invention can suspend or be dissolved in the oil phase and with emulsifying agent or suspending agent and combine.If desired, also can add some sweeting agents and/or flavouring agent and/or toner.

Non-intestinal drug delivery agent comprises injection, cream, unguentum, patch or spray.That the parenterai administration approach comprises is subcutaneous, in the Intradermal, tremulous pulse, vein, muscle, joint, synovial fluid, breastbone, sheath, intralesional, intracranial injection or instillation.Other route of administration can comprise part, rectum, per nasal, through cheek, vagina, Sublingual, mucosa, trachea or urethra.In addition, pharmaceutical composition of the present invention can also suck or implant and accumulate or mode administration such as acupuncture by aerosol.

Pharmaceutical composition of the present invention can be made into aseptic injection, as aseptic water or oil phase suspension.This suspension can use suitable dispersant or wetting agent (as Tween 80) and suspending agent etc. to make by the conventional method of this area.But it can also be at the nontoxic diluent of intestinal external administration or aqueous solution or the suspension in the solvent, as the solution in 1,3 butylene glycol.Relevant available support or solvent comprise mannitol, water, ringer's solution, isotonic sodium chloride etc.In addition, aseptic fixedly oil (bland fixed oil) often is used as the media of solvent or suspending agent, thereby comprises that the multiple soft fixedly oil of synthetic glycerine monoesters or diglyceride all is suitable for.Fatty acid can be used for preparing described injection as octadecenic acid and glyceride ester derivatives thereof (as olive oil or Oleum Ricini, particularly its polyoxyethylene radical derivative) etc.Described oil solution or suspension also can comprise a kind of ethanol dilution agent of long-chain or dispersant or carboxymethyl cellulose or similar other dispersants, and this type of material is usually used in preparing pharmaceutical acceptable emulsion and/or suspending agent.Surfactant that some other preparation is commonly used such as Tweens or Spans and/or other similar emulsifying agents or bioavailability promoter etc. can be used for preparing pharmaceutical composition of the present invention too.

Pharmaceutical composition of the present invention can be made into suppository and passes through rectally, method is that pharmaceutical composition of the present invention is mixed with the non-irritating excipient that suits, the latter is liquid under rectal temperature for solid at room temperature, thereby this suppository is dissolvable in water in the rectum and discharges active ingredient.This type of excipient includes but not limited to: cupu oil, Cera Flava and polyethylene.The local administration preparation of pharmaceutical composition of the present invention (as ointment) can be directly used in the affected part.This type of topical formulations contains active ingredient and pharmaceutically suitable carrier, and the latter includes but not limited to mineral oil, liquid petroleum, white oil, propylene glycol, polyoxyethylene or the polyoxy third desaturation compound, emulsifying is cured or water.

In addition, pharmaceutical composition of the present invention also can be made into lotion or oil preparation.The carrier bag that is suitable for but do not limit fourth: mineral oil, sorbic alcohol monostearate, polysorbate60, spermaceti ester, hexadecanol, 2-octadecanol, benzyl ethanol or water.Pharmaceutical composition of the present invention also can be made into enema etc. and is used for the rectum topical.The topical transdermal patch is also within protection scope of the present invention.But pharmaceutical composition of the present invention is per nasal spraying or inhalation also, promptly by the conventional method of this area, uses benzyl ethanol or other antiseptic, absorption enhancer, fluorocarbon and/or other solubilizing agents or dispersant to make saline solution.

Pharmaceutical composition of the present invention also can pass through drug delivery implant.Adopt the drug delivery implant mode can reach in the administration subject and continue, regularly discharge the effect of pharmaceutical composition of the present invention.In addition, drug delivery implant can also be at local organization and organ site-specific delivery of drugs (Negrin et al., Biomaterials 22 (6): 563,2001) regularly release tech also can be used in the administration of pharmaceutical composition of the present invention, as delayed release capsule, slow release method and the preparation technique for packing (as polymer and liposome) etc. based on the polymer technology.

Patch is included within protection scope of the present invention equally.It comprises basic unit's (as polymer, cloth, yarn and binder) and pharmaceutical composition of the present invention.One side of basic unit can be provided with a protective layer to prevent the outflow of active ingredient.Described patch also can contain a binding agent that is used for fixing, and the latter can be a kind of natural or synthetic material, can temporarily adhere on the skin when it contacts with the administration subject's skin.Binding agent can be a waterproof.

" pharmaceutically suitable carrier " can not destroy the pharmaceutical active of pharmaceutical composition of the present invention, its effective dose simultaneously, and promptly can playing pharmaceutical carrier, to make the consumption of time spent nontoxic to human body." pharmaceutically suitable carrier " includes but not limited to: ion exchange material, aluminium oxide, aluminium stearate, lecithin, self-emulsifying drug delivery system (SEDDS) is as d-alpha-tocopherol cetomacrogol 1000 succinate, the surfactant that pharmaceutical preparatioies such as tween (Tweens) or other similar polymerisation mediums are used, serum albumin such as human serum albumin, buffer substance such as phosphate, glycine, sorbic acid, potassium sorbate, saturated vegetable fatty acid partial glycerol ester admixture, water, salt, electrolyte such as sulfate protamine, phosphoric acid hydrogen two is received, potassium hydrogen phosphate, sodium chloride, zinc salt, silica gel, magnesium silicate etc.Polyvidon, cellulosic material, polyvinyl alcohol, sodium carboxymethyl cellulose, polypropylene acid esters, ethylene-polyoxyethylene-block polymer and wool grease, cyclodextrin such as α-, β-and gamma-cyclodextrin or its promote the drug delivery of pharmaceutical composition of the present invention through all available fourths such as hydroxyalkyl cyclodextrin such as the derivant of chemical modification such as 2-and 3-HP-or other soluble derivatives.

The effective range of wild-scutellaglucone of the present invention and scutellarin or baicalin synergistic effect (molar concentration rate) has been tested by suitable in vitro tests (in vitro assay) and has been allowed.Consumption when WO93/23033 discloses baicalin as cell death inducer, this consumption can be adjusted accordingly according to the difference of route of administration, the state of an illness, patient age, and general oral consumption is: baicalin 100-6000 milligram/day/people, divide and take for 1-3 time; During non-oral administration, its consumption can be 1-100 milligram/day/people.The bibliographical information of clinical antitumor dosage of relevant wild-scutellaglucone of Shang Weijian and scutellarin and suitable route of administration thereof.

Those of ordinary skill in the art should know how to pass through the ordinary skill in the art, according to molar concentration rate disclosed by the invention, wild-scutellaglucone and scutellarin or baicalin are mixed, prepare the synergistic antineoplastic pharmaceutical compositions that has of the present invention.

For the ease of understanding the present invention, the spy enumerates following examples.Its effect should be understood that it is to annotation of the present invention and absolutely not to any type of restriction of the present invention.

The synergism that embodiment 1 wild-scutellaglucone associating scutellarin and baicalin suppress in the human tumor cell line growth in vitro

All kinds of human tumor cell line cell suspensions in the cell culture fluid that contains 10% (little) fetal bovine serum, are seeded in 96 porocyte culture plates with 5 * 103/ holes.After cultivating 24 hours, add wild-scutellaglucone (Kunming Fengshanjian Medicine Research Co., Ltd.) and with scutellarin (Kumin Longjin Medicine Co., Ltd) or baicalin (Sichuan superman's plant development corporation, Ltd.) with variable concentrations than mixing in the adding culture fluid.Cultivate and make MTT mensuration after 72 hours.The suppression ratio of on cell proliferation carries out data analysis with CalcuSyn statistical software and drug combination exponential quantity (CI) method during with the dyeing of tetrazolium (MTT) method and the single usefulness of calculating and coupling wild-scutellaglucone and scutellarin.When CI＜1, be synergism, during CI=1, be summation action; CI＞1 o'clock is antagonism.

Cell proliferation inhibition rate when independent medication and drug combination, and the drug combination exponential quantity sees Table 1-8

All kinds of human tumor cell lines are;

Human hepatoma cell strain HepG2 table 1

Human lung carcinoma cell line A549 table 2

Human stomach cancer cell line MKN28 table 3

Human large intestine cancer cell strain HCT116 table 4

People's esophageal cancer cell strain TE2 table 5

Human leukemia cell line HL60 table 6

Human breast JEG-3 MCF-7 table 7

Human Prostate Cancer Cells strain PC3 table 8

Table 1 wild-scutellaglucone, scutellarin, the HepG2 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		3±2
Wild yellow unit 5		13.3±2.3
				Wild yellow unit 10		42.2±2.2

Wild yellow unit 20		73.7±3 2
				Wild yellow unit 40		91 6±2.2
Scutellarin 2.5		5.2±2.1
				Scutellarin 5		7.7±2.3
Scutellarin 10		43.35±2.7
				Scutellarin 20		86.1±2.9
Scutellarin 40		88.45±2 5
				Baicalin 25		3±2 5
Baicalin 5		7±2
				Baicalin 10		24±2 7
Baicalin 20		42±3 5
				Baicalin 40		80.82±2 8
1∶1	Wild yellow first 5+ wild yellow 5	41.2±2.3	0.977
					Wild yellow first 10+ wild yellow 10	82.2±2.6	0.79
	Wild yellow first 20+ wild yellow 20	93.1±3.1	0.942
					Wild yellow first 40+ wild yellow 40	98.5±3	0.88
1∶2	Wild yellow first 2.5+ wild yellow 5	20.35±2	0 95
					Wild yellow first 5+ wild yellow 10	67.8±3.1	0.616
	Wild yellow first 10+ wild yellow 20	91.1±3.5	0.53
					Wild yellow first 20+ wild yellow 40	98±3	0.464
1∶4	Wild yellow first 2.5+ wild yellow 10	58.2±3	0.887
					Wild yellow first 5+ wild yellow 20	82.58±2	0.92
	Wild yellow first 10+ wild yellow 40	95.5±3	0.945
					Wild yellow first 20+ wild yellow 80	98.8±3	0.978
1∶1	Wild yellow first 5+ Huang 5	56.8±3.2	0.567
					Wild yellow first 10+ Huang 10	78.8±2.5	0.669
	Wild yellow first 20+ Huang 20	89.9±3	0 858
					Wild yellow first 40+ Huang 40	97.2±2.8	0.863
1∶2	Wild yellow first 2.5+ Huang 5	49.8±3.5	0.452

	Wild yellow first 5+ Huang 10	86.7±3	0.336
					Wild yellow first 10+ Huang 20	90 3±3 2	0.558
	Wild yellow first 20+ Huang 40	98.8±3	0 3587
				1∶4	Wild yellow first 2.5+ Huang 10	78.4±2.7	0 347
	Wild yellow first 5+ Huang 20	85.02±3	0 545
					Wild yellow first 10+ Huang 40	95.7±3	0.522
	Wild yellow first 20+ Huang 80	99±1	0.47

Table 2 wild-scutellaglucone, scutellarin, the A549 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		7.23±2.2
Wild yellow unit 5		24.52±2.1
				Wild yellow unit 10		78.57±3.1
Wild yellow unit 20		90.8±3
				Wild yellow unit 40		95.25±2.2
Scutellarin 2.5		1±2.1
				Scutellarin 5		7.7±3.3
Scutellarin 10		32.33±2.7
				Scutellarin 20		62.65±2.5
Scutellarin 40		91±2.7
				Baicalin 2.5		8.73±2.3
Baicalin 5		23±2
				Baicalin 10		43.5±2.5
Baicalin 20		49.8±3.2
				Baicalin 40		87.82±2.5
11	Wild yellow first 5+ wild yellow 5	65.2±2.3	0 745
					Wild yellow first 10+ wild yellow 10	82.2±2.5	0.989
	Wild yellow first 20+ wild yellow 20	96.5±3.2	0.88

	Wild yellow first 40+ wild yellow 40	99±1.2	0.988
				1∶2	Wild yellow first 2.5+ wild yellow 5	45.5±2	0.717
	Wild yellow first 5+ wild yellow 10	78.8±3.2	0.739
					Wild yellow first 10+ wild yellow 20	95 2±3.5	0.7
	Wild yellow first 20+ wild yellow 40	98.5±2	0.83
				1∶4	Wild yellow first 2.5+ wild yellow 10	59.5±3	0.843
	Wild yellow first 5+ wild yellow 20	87.55±2.5	0.853
					Wild yellow first 10+ wild yellow 40	96.7±3	0.922
	Wild yellow first 20+ wild yellow 80	99±3	1
				1∶1	Wild yellow first 5+ Huang 5	56.8±3	0.897
	Wild yellow first 10+ Huang 10	87.8±2.2	0.707
					Wild yellow first 20+ Huang 20	96.5±3.5	0.691
	Wild yellow first 40+ Huang 40	98.5±2.7	0.88
				1∶2	Wild yellow first 2.5+ Huang 5	49.8±3.2	0.719
	Wild yellow first 5+ Huang 10	85.7±2.5	0.5
					Wild yellow first 10+ Huang 20	95.2±3.5	0.5
	Wild yellow first 20+ Huang 40	98.72±3	0.476
				1∶4	Wild yellow first 2.5+ Huang 10	77±2.5	0.515
	Wild yellow first 5+ Huang 20	89.98±2	0.56
					Wild yellow first 10+ Huang 40	96.58±3	0.56
	Wild yellow first 20+ Huang 80	99±3	0.537

Table 3 wild-scutellaglucone, scutellarin, the MKN28 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		6.8±2.1
Wild yellow unit 5		23.65±2.5
				Wild yellow unit 10		41±3.1
Wild yellow unit 20		55.2±3

Wild yellow unit 40		81.2±2.2
				Scutellarin 2.5		18.83±2.2
Scutellarin 5		21.23±3.5
				Scutellarin 10		31.65±2.8
Scutellarin 20		35.34±2.8
				Scutellarin 40		75 34±2 7
Baicalin 2.5		2±2.5
				Baicalin 5		3.55±2
Baicalin 10		10±2.5
				Baicalin 20		38.85±3.5
Baicalin 40		72.05±2.7
				1∶1	Wild yellow first 5+ wild yellow 5	47.2±2.7	0.657
	Wild yellow first 10+ wild yellow 10	65 5±2.5	0.666
					Wild yellow first 20+ wild yellow 20	81±3.3	0.662
	Wild yellow first 40+ wild yellow 40	93.8±2.2	0.4658
				1∶2	Wild yellow first 2.5+ wild yellow 5	45.3±2	0.5
	Wild yellow first 5+ wild yellow 10	70±3.5	0.368
					Wild yellow first 10+ wild yellow 20	84.2±3.2	0.342
	Wild yellow first 20+ wild yellow 40	94.3±2	0.252
				1∶4	Wild yellow first 2.5+ wild yellow 10	72.22±3.2	0.245
	Wild yellow first 5+ wild yellow 20	85.82±2.2	0.21
					Wild yellow first 10+ wild yellow 40	90.5±3	0.272
	Wild yellow first 20+ wild yellow 80	95±3	0.285
				1∶1	Wild yellow first 5+ Huang 5	17 8±3 2	1.5
	Wild yellow first 10+ Huang 10	45 9±2.1	1.19
					Wild yellow first 20+ Huang 20	75.3±3.5	1
	Wild yellow first 40+ Huang 40	92.75±2.5	0.8
				1∶2	Wild yellow first 2.5+ Huang 5	17.2±3.2	0.99
	Wild yellow first 5+ Huang 10	43.7±2.7	0.849

	Wild yellow first 10+ Huang 20	72.2±3.1	0 789
					Wild yellow first 20+ Huang 40	92±3	0.623
1∶4	Wild yellow first 2.5+ Huang 10	27.5±2.5	0.99
					Wild yellow first 5+ Huang 20	58.9±2.1	0.88
	Wild yellow first 10+ Huang 40	81 3±2.8	0.9
					Wild yellow first 20+ Huang 80	91±3	1

Table 4 wild-scutellaglucone, scutellarin, the HCT116 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		19.6±2
Wild yellow unit 5		25.2±2.3
				Wild yellow unit 10		78.35±2.7
Wild yellow unit 20		90.7±3.1
				Wild yellow unit 40		95.2±2.5
Scutellarin 2.5		10.05±2.5
				Scutellarin 5		15.1±3
Scutellarin 10		49±2.2
				Scutellarin 20		83.7±2.2
Scutellarin 40		95±2.8
				Baicalin 2.5		8 73±2.1
Baicalin 5		13.88±2.2
				Baicalin 10		18±2.2
Baicalin 20		49.45±3.1
				Baicalin 40		90.82±2.5
1∶1	Wild yellow first 5+ wild yellow 5	65.2±2.2	0.9428
					Wild yellow first 10+ wild yellow 10	82.2±2.3	1.1
	Wild yellow first 20+ wild yellow 20	95.1±3.2	1
					Wild yellow first 40+ wild yellow 40	98.5±2.1	1

1∶2	Wild yellow first 2.5+ wild yellow 5	45.35±2	1
					Wild yellow first 5+ wild yellow 10	77 8±3.2	0.952
	Wild yellow first 10+ wild yellow 20	91.2±3.1	1
					Wild yellow first 20+ wild yellow 40	98±29	0.93
1∶4	Wild yellow first 2.5+ wild yellow 10	75±3.5	0.822
					Wild yellow first 5+ wild yellow 20	90.02±2.5	0.923
	Wild yellow first 10+ wild yellow 40	97.2±2.1	0.912
					Wild yellow first 20+ wild yellow 80	99±3	1
1∶1	Wild yellow first 5+ Huang 5	56.8±2.2	0.95
					Wild yellow first 10+ Huang 10	87.8±2.2	0.706
	Wild yellow first 20+ Huang 20	95.5±2.5	0.75
					Wild yellow first 40+ Huang 40	98.5±2.5	0.777
1∶2	Wild yellow first 2.5+ Huang 5	49.8±3.5	0.727
					Wild yellow first 5+ Huang 10	86.7±2.3	0.476
	Wild yellow first 10+ Huang 20	95.2±3.1	0.49
					Wild yellow first 20+ Huang 40	98.72±3	0.439
1∶4	Wild yellow first 2.5+ Huang 10	76.2±2.5	0.5199
					Wild yellow first 5+ Huang 20	85.7±2.2	0.712
	Wild yellow first 10+ Huang 40	95.8±2.8	0.638
					Wild yellow first 20+ Huang 80	99±3	0.528

Table 5 wild-scutellaglucone, scutellarin, the TE2 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		2.03±2.2
Wild yellow unit 5		25±2.2
				Wild yellow unit 10		52.5±3.2
Wild yellow unit 20		73 5±3
				Wild yellow unit 40		75.8±2.5

Scutellarin 25		4.7±2.2
				Scutellarin 5		12.97±3.1
Scutellarin 10		27.1±2.7
				Scutellarin 20		66±2.9
Scutellarin 40		84 62±2.5
				Baicalin 2.5		7.5±2.2
Baicalin 5		16.3±2.5
				Baicalin 10		27.2±2.3
Baicalin 20		40.1±3.1
				Baicalin 40		72.3±2.5
1∶1	Wild yellow first 5+ wild yellow 5	36±2.2	0.973
					Wild yellow first 10+ wild yellow 10	64.5±2.5	0.99
	Wild yellow first 20+ wild yellow 20	85.8±2.2	0.996
					Wild yellow first 40+ wild yellow 40	97±1.5	0.761
1∶2	Wild yellow first 2.5+ wild yellow 5	35±3	0.736
					Wild yellow first 5+ wild yellow 10	61.7±3.3	0.784
	Wild yellow first 10+ wild yellow 20	87.9±2.1	0.661
					Wild yellow first 20+ wild yellow 40	97.5±2	0.503
1∶4	Wild yellow first 2.5+ wild yellow 10	47.2±3	0.9
					Wild yellow first 5+ wild yellow 20	87±2.8	0.567
	Wild yellow first 10+ wild yellow 40	97±3	0.458
					Wild yellow first 20+ wild yellow 80	99±3	0.481
1∶1	Wild yellow first 5+ Huang 5	25.2±3	1.25
					Wild yellow first 10+ Huang 10	52.9±1.7	1.1
	Wild yellow first 20+ Huang 20	83 41±2.5	0.818
					Wild yellow first 40+ Huang 40	95.1±28	0 69
1∶2	Wild yellow first 2.5+ Huang 5	13±3.2	1.696
					Wild yellow first 5+ Huang 10	29.5±2.5	1.567
	Wild yellow first 10+ Huang 20	67 1±3.2	0.99

	Wild yellow first 20+ Huang 40	87 2±2.5	0.85
				1∶4	Wild yellow first 2.5+ Huang 10	40 7±2 2	0.86
	Wild yellow first 5+ Huang 20	61.1±2	0.912
					Wild yellow first 10+ Huang 40	83±3.2	0.778
	Wild yellow first 20+ Huang 80	95±3	0.578

Table 6 wild-scutellaglucone, scutellarin, the HL60 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		7.3±2.5
Wild yellow unit 5		24.4±2.5
				Wild yellow unit 10		47±2.5
Wild yellow unit 20		71.5±3.5
				Wild yellow unit 40		87.7±2.5
Scutellarin 2.5		2.25±2.7
				Scutellarin 5		8.64±3.2
Scutellarin 10		37±2.2
				Scutellarin 20		64.2±2.7
Scutellarin 40		88.5±2.5
				Baicalin 2.5		3.5±2.2
Baicalin 5		29.22±1.2
				Baicalin 10		56.1±2.3
Baicalin 20		71,3±3.2
				Baicalin 40		82 1±2.2
1∶1	Wild yellow first 5+ wild yellow 5	62 1±2.1	0.597
					Wild yellow first 10+ wild yellow 10	80 1±2.2	0.724
	Wild yellow first 20+ wild yellow 20	90±3	0.929
					Wild yellow first 40+ wild yellow 40	96.7±2.1	0.976
1∶2	Wild yellow first 2.5+ wild yellow 5	51±2.5	0.552

	Wild yellow first 5+ wild yellow 10	81.5±2.2	0.512
					Wild yellow first 10+ wild yellow 20	87±3.2	0.822
	Wild yellow first 20+ wild yellow 40	95±2.9	0 95
				1∶4	Wild yellow first 2.5+ wild yellow 10	80.1±3 2	0.44
	Wild yellow first 5+ wild yellow 20	85.9±2.2	0.72
					Wild yellow first 10+ wild yellow 40	95±2.1	0.812
	Wild yellow first 20+ wild yellow 80	98±3	1
				1∶1	Wild yellow first 5+ Huang 5	49.02±2.1	0.88
	Wild yellow first 10+ Huang 10	77.12±2.5	0.816
					Wild yellow first 20+ Huang 20	90±2.7	0.892
	Wild yellow first 40+ Huang 40	97±2.5	0.812
				1∶2	Wild yellow first 2.5+ Huang 5	19±3	1.55
	Wild yellow first 5+ Huang 10	59.9±2.1	1
					Wild yellow first 10+ Huang 20	85.7±3.1	0.855
	Wild yellow first 20+ Huang 40	97±3	0.61
				1∶4	Wild yellow first 2.5+ Huang 10	18±2.1	2.65
	Wild yellow first 5+ Huang 20	71.6±2.3	1.2
					Wild yellow first 10+ Huang 40	95±2.8	0.7
	Wild yellow first 20+ Huang 80	99±3	0.52

Table 7 wild-scutellaglucone, scutellarin, the MCF-7 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		6.5±2.1
Wild yellow unit 5		33.6±2.2
				Wild yellow unit 10		62 1±2 8
Wild yellow unit 20		85±2.1
				Wild yellow unit 40		95.8±25
Scutellarin 2.5		5±2.5

Scutellarin 5		20 71±3.2
				Scutellarin 10		71±2.2
Scutellarin 20		87.5±2 5
				Scutellarin 40		95 57±2 2
Baicalin 2.5		4.2±2 1
				Baicalin 5		28.4±2.3
Baicalin 10		48.8±2.5
				Baicalin 20		82.3±2.1
Baicalin 40		93.03±2.5
				1∶1	Wild yellow first 5+ wild yellow 5	61.2±2.1	0.958
	Wild yellow first 10+ wild yellow 10	88.12±2.2	0.92
					Wild yellow first 20+ wild yellow 20	97.2±2.2	0.888
	Wild yellow first 40+ wild yellow 40	99.2±2.1	0.972
				1∶2	Wild yellow first 2.5+ wild yellow 5	51±2	0.868
	Wild yellow first 5+ wild yellow 10	82.5±3.5	0.858
					Wild yellow first 10+ wild yellow 20	95±2.2	0.895
	Wild yellow first 20+ wild yellow 40	98.8±2.2	0.9
				1∶4	Wild yellow first 2.5+ wild yellow 10	82 55±2.5	0.715
	Wild yellow first 5+ wild yellow 20	92.9±2.2	0.895
					Wild yellow first 10+ wild yellow 40	97.9±1.9	0.997
	Wild yellow first 20+ wild yellow 80	99.5±3.2	1
				1∶1	Wild yellow first 5+ Huang 5	58±2.2	0.947
	Wild yellow first 10+ Huang 10	82.8±2.2	1
					Wild yellow first 20+ Huang 20	95.5±2.5	0.97
	Wild yellow first 40+ Huang 40	98.8±2.5	0.99
				1∶2	Wild yellow first 2.5+ Huang 5	59.8±3.5	0.66
	Wild yellow first 5+ Huang 10	89.7±2.3	0.55
					Wild yellow first 10+ Huang 20	95±3	0.746
	Wild yellow first 20+ Huang 40	98±3	0.931

1∶4	Wild yellow first 2.5+ Huang 10	82.5±2.5	0.6
					Wild yellow first 5+ Huang 20	92.02±2.2	0.77
	Wild yellow first 10+ Huang 40	96.7±2.8	0 97
					Wild yellow first 20+ Huang 80	99±2	1

Table 8 wild-scutellaglucone, scutellarin, the PC3 cell increment suppression ratio when the independent medication of baicalin and wild-scutellaglucone associating scutellarin or baicalin medication, and drug combination index

Single-dose thing activity (μ m)	Combination medicine activity (μ m)	Inhibitory rate of cell growth (%)	Drug combination coefficient value (CI)
				Wild yellow unit 2.5		7 7±2.5
Wild yellow unit 5		22.7±3.6
				Wild yellow unit 10		51±3.8
Wild yellow unit 20		70±2.7
				Wild yellow unit 40		91.8±2.5
Scutellarin 2.5		1±2.5
				Scutellarin 5		17.7±3.1
Scutellarin 10		47±2.7
				Scutellarin 20		61±2.2
Scutellarin 40		90±2.9
				Baicalin 2.5		2±2.5
Baicalin 5		19±3.3
				Baicalin 10		48±3.5
Baicalin 20		67±2.7
				Baicalin 40		91.9±3.2
1∶1	Wild yellow first 5+ wild yellow 5	47.9±2.7	0.877
					Wild yellow first 10+ wild yellow 10	79±3.2	0.842
	Wild yellow first 20+ wild yellow 20	91±3.1	1
					Wild yellow first 40+ wild yellow 40	99±2.5	0.636
1∶2	Wild yellow first 2.5+ wild yellow 5	47±2.9	0.638
					Wild yellow first 5+ wild yellow 10	79±3.2	0.622

	Wild yellow first 10+ wild yellow 20	91±2.8	0.765
					Wild yellow first 20+ wild yellow 40	98±2 7	0.71
1∶4	Wild yellow first 2.5+ wild yellow 10	58±2.5	0.826
					Wild yellow first 5+ wild yellow 20	78±2 5	1
	Wild yellow first 10+ wild yellow 40	97±2.9	0.743
					Wild yellow first 20+ wild yellow 80	99±3 2	0.88
1∶1	Wild yellow first 5+ Huang 5	49±2.7	0.899
					Wild yellow first 10+ Huang 10	81±2.5	0.818
	Wild yellow first 20+ Huang 20	92±3.5	0.97
					Wild yellow first 40+ Huang 40	99±2.2	0.636
1∶2	Wild yellow first 2.5+ Huang 5	52±3.2	0.616
					Wild yellow first 5+ Huang 10	68.8±2.3	0.858
	Wild yellow first 10+ Huang 20	87±3.2	0.977
					Wild yellow first 20+ Huang 40	97±3	0.885
1∶4	Wild yellow first 2.5+ Huang 10	72.2±2.2	0.65
					Wild yellow first 5+ Huang 20	82±2.5	0.99
	Wild yellow first 10+ Huang 40	95.1±2.8	0.97
					Wild yellow first 20+ Huang 80	99±3.2	0.88

Annotate: Ye Huangyuan=wild-scutellaglucone; Wild Huang=scutellarin; Huang=baicalin

Suppression ratio %; Mean value SD, n=3

When CI＜1, be synergism, during CI=1, be summation action; CI＞1 o'clock is antagonism.

Table 1-8 demonstrates at wild-scutellaglucone scutellarin and baicalin is about (1: 2) to the molar concentration rate of the IC50 of each cell strain, and be presented near this concentration ratio the zone (1: 1～1: 4) good drug combination index is all arranged, can show significantly that wild-scutellaglucone and scutellarin or baicalin are to each human tumor cell line; Human hepatoma cell strain HepG2, people's large intestine HCT116, human lung carcinoma cell line A549, human stomach cancer cell line MKN45, esophageal cancer cell strain TE2, human leukemia cell line HL60, human breast JEG-3 MCF-7, Human Prostate Cancer Cells strain PC3 has good drug combination effect.

Embodiment 2 wild-scutellaglucones associating scutellarin is to transplanting the antitumor synergism of entity tumor

With the strain of mice B16 melanoma cell at In vitro culture after two generations, with 2 * 10 ⁶Cell/only the be inoculated in female C57BL/6 of laboratory animal (body weight is about 20 grams) mice oxter is subcutaneous.Inoculate the second largest random packet in back, and begin administration by the 0.1ml/10g body weight.Wild-scutellaglucone (Kunming Fengshanjian Medicine Research Co., Ltd.) and scutellarin (Kumin Longjin Medicine Co., Ltd) are united different administering mode grouping carrying out antitumor tests such as closing administration with individually dosed.Every group laboratory animal is 10.Measure the weight of animals before the administration, test and took off neck execution behind the title the weight of animals on 15th, strip tumor block organization and weigh.The mensuration of tumour inhibiting rate is by computing formula; Tumour inhibiting rate=(1-treatment group tumor weight/blank group tumor is heavy) * 100% calculates the heavy suppression ratio of tumor and carries out statistics (t check) and handle.

Result of the test sees Table 9

Table 9

Grouping dosed administration schedule body weight subtracts heavy (g) tumour inhibiting rate number of animals (only) of tumor

The few rate mean value SD of mg/kg, % beginning/end

％

Matched group-＜02 28 ± 0 08 10/10

Wild yellow first 30 abdominal cavity 1-10＜51 71 ± 0 09 25 10/10

Wild yellow glycoside 25 abdominal cavity 1-10＜51 81 ± 0 102 20 6 10/10

Wild yellow glycoside 50 abdominal cavity 1-10＜51 725 ± 0 12 24 3 10/10

Wild yellow glycoside 100 abdominal cavity 1-10＜51 59 ± 0 11 34 2 10/10

Wild yellow glycoside 200 abdominal cavity 1-10＜51 451 ± 0 106 36 36 10/10

Each abdominal cavity 1-10＜51 65 ± 0 08 27 6 of wild yellow unit+wild yellow glycoside 30+25 ^*# 10/10

Each abdominal cavity 1-10＜51 525 ± 0 12 33 1 of wild yellow unit+wild yellow glycoside 30+50 ^*# 10/10

Each abdominal cavity 1-10＜51 15 ± 0 09 49 55 of wild yellow unit+wild yellow glycoside 30+100 ^*# 10/10

Each abdominal cavity 1-10＜50 98 ± 0 12 57 of wild yellow unit+wild yellow glycoside 30+200 ^*# 10/10

5-fluorouracil 10 subcutaneous 1-10＜51 39 ± 01 39 10/10

Wild yellow unit=wild-scutellaglucone, wild yellow glycoside=scutellarin

^*P＜0.1 and single scutellarin tuple ratio of using, ^*P＜0.01 and single scutellarin tuple ratio of using

#P＜0.01 with single with scutellarin group ratio

Visible wild-scutellaglucone of result of the test and scutellarin have embodied tangible antitumor potentiation when share.Wild-scutellaglucone+scutellarin 30+50mg/kg, wild-scutellaglucone+scutellarin 30+100mg/kg, each group of wild-scutellaglucone+scutellarin 30+200mg/kg all has significant difference on the statistics with single comparing with baicalin tuple and baicalin respectively.Wild-scutellaglucone+scutellarin 30+25mg/kg also presented certain antitumor potentiation but effect not as above-mentioned two groups obviously.

Change and can see from the weight of animals, each combination group is not seen has any toxicity to strengthen trend.

Near wild-scutellaglucone and the scutellarin zone 1: 0.5～1: 4 concentration ratio has collaborative medication effect, and the collaborative medication effect near the zone 1: 1～1: 4 concentration ratio is more obvious.As seen animal test results has been supported the result of in vitro tests significantly.

As seen wild-scutellaglucone and scutellarin share entity tumor are had good synergistic antitumor effect.

Embodiment 3 wild-scutellaglucones associating scutellarin is to transplanting the antitumor synergism of neoplastic hematologic disorder

With the mouse leukemia cell strain L1210 of growth animated period, with 10 ⁵Cell/only be inoculated in the female BDF1 of laboratory animal (body weight is about the 20 grams) mouse peritoneal.Inoculate back second day random packet, and begin administration by the 0.1ml/10g body weight.Wild-scutellaglucone (Kunming Fengshanjian Medicine Research Co., Ltd.) and scutellarin (Kumin Longjin Medicine Co., Ltd) are united different administering mode grouping carrying out antitumor tests such as closing administration with individually dosed.Every group laboratory animal is 10.The record animals survived time.(increase of life span, the curative effect of each treatment group is judged in variation ILS) with the mice increase in life span.The mensuration of increase in life span is by computing formula; Increase in life span=(treatment treated animal life span/blank treated animal life span-1) * 100% also carries out statistics (t check) and handles.

Result of the test sees Table 10

Table 10

Grouping dosed administration schedule The average survival time number of days ILS (%)

Mg/kg mean value SD

Matched group-10.2 ± 1.23

Wild yellow first 30 abdominal cavity 1-10 14.05 ± 2.36 37.7

Wild yellow glycoside 25 abdominal cavity 1-10 11.8 ± 1.72 15.7

Wild yellow glycoside 50 abdominal cavity 1-10 12.4 ± 2.32 21.57

Wild yellow glycoside 100 abdominal cavity 1-10 15.15 ± 2.7 48.5

Wild yellow glycoside 200 abdominal cavity 1-10 18.25 ± 3.3 79

Each abdominal cavity 1-10 14.85 ± 1.9 45.6 of wild yellow unit+wild yellow glycoside 30+25 ^*#

Each abdominal cavity 1-10 16.25 ± 2.7 59 of wild yellow unit+wild yellow glycoside 30+50 ^*#

Wild yellow unit+wild each abdominal cavity 1-10 19.2 of yellow glycoside 30+100 ± 2.57 88.2 ^{* *}#

Each abdominal cavity 1-10 21.9 ± 2.1 114.7 of wild yellow unit+wild yellow glycoside 30+200 ^{* *}#

Cytosine arabinoside (positive 10 abdominal cavity 1-5 18.2 ± 2.5 78

Matched group)

Wild yellow unit=wild-scutellaglucone, wild yellow glycoside=scutellarin

^*P＜05 and single scutellarin tuple ratio of using, ^*P＜0.05 and single scutellarin tuple ratio of using, ^{* *}P＜0 01 and single, #P＜0.01 with scutellarin tuple ratio with single with scutellarin group ratio

Visible wild-scutellaglucone of result of the test and scutellarin have embodied tangible antitumor potentiation when share.Wild-scutellaglucone+scutellarin 30+50mg/kg, wild-scutellaglucone+scutellarin 30+100mg/kg, each group of wild-scutellaglucone+scutellarin 30+200mg/kg all has significant difference on the statistics with single comparing with scutellarin tuple and scutellarin respectively.Wild-scutellaglucone+scutellarin 30+25mg/kg also presented certain antitumor potentiation but effect not as above-mentioned three groups obviously.

Near wild-scutellaglucone and the scutellarin zone 1: 0.5～1: 4 concentration ratio has collaborative medication effect, and the collaborative medication effect near the zone 1: 1～1: 4 concentration ratio is more obvious.As seen animal test results has been supported the result of in vitro tests significantly.

As seen to share blood be that tumor has good synergistic antitumor effect for wild-scutellaglucone and scutellarin.

Embodiment 4 wild-scutellaglucones associating baicalin is to transplanting the antitumor synergism of entity tumor

The strain of mice B16 melanoma cell is at In vitro culture after two generations, subcutaneous with 2 * 106 cells/only the be inoculated in female C57BL/6 of laboratory animal (body weight is about 20 grams) mice oxter.Inoculate back second day random packet, and begin administration by the 0.1ml/10g body weight.Wild-scutellaglucone (Kunming Fengshanjian Medicine Research Co., Ltd.) and baicalin (Sichuan superman's plant development corporation, Ltd.) are united different administering mode grouping carrying out antitumor tests such as closing administration with individually dosed.Every group laboratory animal is 10.Measure the weight of animals before the administration, test and took off neck execution behind the title the weight of animals on 15th, strip tumor block organization and weigh.The mensuration of tumour inhibiting rate is by computing formula; Tumour inhibiting rate=(1-treatment group tumor weight/blank group tumor is heavy) * 100% calculates the heavy suppression ratio of tumor and carries out statistics (t check) and handle.

Result of the test sees Table 11

Table 11

Grouping dosed administration schedule heavy (g) tumour inhibiting rate number of animals (only) of tumor of losing weight

Mg/kg leads mean value SD, % beginning/end

％

Matched group-＜02 28 ± 0 08 10/10

Wild yellow first 30 abdominal cavity 1-10＜51 71 ± 0 09 25 10/10

Yellow glycoside 25 abdominal cavity 1-10＜51 81 ± 01 20 6 10/10

Yellow glycoside 50 abdominal cavity 1-10＜51 77 ± 0 10 22 36 10/10

Yellow glycoside 100 abdominal cavity 1-10＜51 525 ± 0 14 33 1 10/10

Yellow glycoside 200 abdominal cavity 1-10＜51 458 ± 0 08 304 10/10

Each abdominal cavity 1-10＜51 62 ± 01 29 of wild yellow unit+yellow glycoside 30+25 ^*# 10/10

Each abdominal cavity 1-10＜51 586 ± 0 08 30 4 of wild yellow unit+yellow glycoside 30+50 ^*# 10/10

Each abdominal cavity 1-10＜51 141 ± 0 09 50 of wild yellow unit+yellow glycoside 30+100 ^*# 10/10

Each abdominal cavity 1-10＜50 982 ± 0 128 57 of wild yellow unit+yellow glycoside 30+200 ^*# 10/10

5-fluorouracil 10 subcutaneous 1-10＜51 35 ± 01 38 10/10

Wild yellow unit=wild-scutellaglucone, yellow glycoside=baicalin

^*P＜0.05 and single baicalin tuple ratio of using, ^*P＜0.01 and single baicalin tuple ratio of using

#P＜0.01 with single with scutellarin group ratio

Visible wild-scutellaglucone of result of the test and baicalin have embodied tangible antitumor potentiation when share.Wild-scutellaglucone+baicalin 30+50mg/kg, wild-scutellaglucone+baicalin 30+100mg/kg, each group of wild-scutellaglucone+baicalin 30+200mg/kg all has significant difference on the statistics with single comparing with scutellarin tuple and baicalin respectively.Wild-scutellaglucone+baicalin 30+25mg/kg also presented certain antitumor potentiation but effect not as above-mentioned three groups obviously.

Change and can see from the weight of animals, each combination group is not seen has any toxicity to strengthen trend.

Near wild-scutellaglucone and the baicalin zone 1: 0.5～1: 4 concentration ratio has collaborative medication effect, and the collaborative medication effect near the zone 1: 1～1: 4 concentration ratio is more obvious.As seen animal test results has been supported the result of in vitro tests significantly.

As seen wild-scutellaglucone and baicalin share entity tumor are had good synergistic antitumor effect.

Embodiment 5 wild-scutellaglucones associating baicalin is to transplanting the antitumor synergism of neoplastic hematologic disorder

With the mouse leukemia cell strain L1210 of growth animated period, with 10 ⁵Cell/only be inoculated in the female BDF1 of laboratory animal (body weight is about the 20 grams) mouse peritoneal.Inoculate back second day random packet, and begin administration by 0 1ml/10g body weight.Wild-scutellaglucone (Kunming Fengshanjian Medicine Research Co., Ltd.) and baicalin (Sichuan superman's plant development corporation, Ltd.) are united different administering mode grouping carrying out antitumor tests such as closing administration with individually dosed.Every group laboratory animal is 10.The record animals survived time.(increase of life span, the curative effect of each treatment group is judged in variation ILS) with the mice increase in life span.The mensuration of increase in life span is by computing formula; Increase in life span=(treatment treated animal life span/blank treated animal life span-1) * 100% is also added up word (t check) and is handled.

Result of the test sees Table 12

Table 12

Grouping dosed administration schedule The average survival time number of days ILS (%)

Mg/kg mean value SD

Matched group-10.2 ± 1.23

Wild yellow first 30 abdominal cavity 1-10 14.05 ± 2.36 37.7

Yellow glycoside 25 abdominal cavity 1-10 11.49 ± 2.4 12.6

Yellow glycoside 50 abdominal cavity 1-10 13.25 ± 3 29.9

Yellow glycoside 100 abdominal cavity 1-10 15.15 ± 2.7 48.5

Yellow glycoside 200 abdominal cavity 1-10 16.85 ± 3.25 65.2

Each abdominal cavity 1-10 14.7 ± 1.9 44.1 of wild yellow unit+yellow glycoside 30+25 ^*#

Wild yellow each abdominal cavity 1-10 17.35 of unit+yellow glycoside 30+50 ± 2.38 70.1 ^*#

Wild yellow each abdominal cavity 1-10 18.65 of unit+yellow glycoside 30+100 ± 2.69 82.8 ^*#

Each abdominal cavity 1-10 22 ± 3 115.7 of wild yellow unit+yellow glycoside 30+200 ^*#

Cytosine arabinoside (positive 10 abdominal cavity 1-5 18.2 ± 2.5 78

Matched group)

Wild yellow unit=wild-scutellaglucone, yellow glycoside=baicalin

^*P＜0.05 and single scutellarin tuple ratio of using, ^*P＜0.01 and single scutellarin tuple ratio of using

#P＜0.01 with single with baicalin group ratio

Visible wild-scutellaglucone of result of the test and baicalin have embodied tangible antitumor potentiation when share.Wild-scutellaglucone+baicalin 30+50mg/kg, wild-scutellaglucone+baicalin 30+100mg/kg, each group of wild-scutellaglucone+baicalin 30+200mg/kg all has significant difference on the statistics with single comparing with scutellarin tuple and baicalin respectively.Wild-scutellaglucone+baicalin 30+25mg/kg also presented certain antitumor potentiation but effect not as above-mentioned three groups obviously.

Near wild-scutellaglucone and the baicalin zone 1: 0.5～1: 4 concentration ratio has collaborative medication effect, and the collaborative medication effect near the zone 1: 1～1: 4 concentration ratio is more obvious.As seen animal test results has been supported the result of in vitro tests significantly.

As seen to share blood be that tumor has good synergistic antitumor effect for wild-scutellaglucone and baicalin.

Each above listed pertinent literature is all introduced the application as a reference with a full piece of writing.Many aspects involved in the present invention have been done as above and have been set forth.Yet, it should be understood that under the prerequisite of spirit that does not depart from the present invention and scope, any modification of foregoing description is all allowed.Equally, similarly situation is also included within the claim.

Claims (9)

1. wild-scutellaglucone has purposes in the synergistic antitumor drug in preparation to following general formula (I) chemical compound:

Wherein, R ₁Represent the glucal acidic group, R ₂Represent hydrogen or hydroxyl; The molar concentration rate of described wild-scutellaglucone and general formula (I) chemical compound is 2: 1 to 1: 4.

2. the purposes of claim 1, wherein said tumor is that entity tumor or blood are tumor; The molar concentration rate of described wild-scutellaglucone and general formula (I) chemical compound is 1: 1 to 1: 4.

3. the purposes of claim 1, wherein said tumor is selected from melanoma, hepatocarcinoma, gastric cancer, pulmonary carcinoma, colorectal cancer, esophageal carcinoma, breast carcinoma, carcinoma of prostate and leukemia.

4. the pharmaceutical composition that has the synergistic antitumor effect, said composition comprise wild-scutellaglucone and following general formula (I) chemical compound:

Wherein, R ₁Represent the glucal acidic group, R ₂Represent hydrogen or hydroxyl; It is characterized in that the molar concentration rate of described wild-scutellaglucone and general formula (I) chemical compound is 2: 1 to 1: 4.

5. the pharmaceutical composition of claim 4, wherein said tumor is that entity tumor or blood are tumor; The molar concentration rate of described wild-scutellaglucone and general formula (I) chemical compound is 1: 1 to 1: 4.

6. the pharmaceutical composition of claim 5, wherein said tumor is selected from melanoma, hepatocarcinoma, gastric cancer, pulmonary carcinoma, colorectal cancer, esophageal carcinoma, breast carcinoma, carcinoma of prostate and leukemia.

7. prepare the method for arbitrary pharmaceutical composition of claim 4～6, this method comprises wild-scutellaglucone and at least a compound that is selected from following general formula (I):

Wherein, R ₁Represent the glucal acidic group, R ₂Represent hydrogen or hydroxyl.

8. the method for claim 7, this method comprise that also adding pharmaceutically acceptable additive is mixed with suitable dosage form with described mixture.

9. arbitrary pharmaceutical composition of claim 4～6 is in the purposes of preparation in the antitumor drug.