CN1875958A - Pharmaceutical composition of scutellarin and baicalin with synergistic tumor resistance function - Google Patents
Pharmaceutical composition of scutellarin and baicalin with synergistic tumor resistance function Download PDFInfo
- Publication number
- CN1875958A CN1875958A CNA2006100775706A CN200610077570A CN1875958A CN 1875958 A CN1875958 A CN 1875958A CN A2006100775706 A CNA2006100775706 A CN A2006100775706A CN 200610077570 A CN200610077570 A CN 200610077570A CN 1875958 A CN1875958 A CN 1875958A
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- CN
- China
- Prior art keywords
- wild
- yellow
- wild yellow
- scutellarin
- baicalin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
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- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
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- 235000013355 food flavoring agent Nutrition 0.000 description 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
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- 239000008187 granular material Substances 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
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- 238000000099 in vitro assay Methods 0.000 description 1
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- 235000019388 lanolin Nutrition 0.000 description 1
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- 239000007937 lozenge Substances 0.000 description 1
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- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
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Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to a pharmaceutical composition with synergic anti-tumor action containing erigeron breviscapus, scutellarin or baicalin. the invention also provides the method for preparation and use of the pharmaceutical composition.
Description
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:
Wherein, when D1, D2 are respectively medicine 1 and medicine 2 independent uses, 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.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, and the molar concentration rate of wherein said wild-scutellaglucone and general formula (I) chemical compound is 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.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, has synergism.Thereby 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 separate from certain plants such as Herba Scutellariae Barbatae, Radix Scutellariae and obtain.Wild-scutellaglucone of the present invention, scutellarin or baicalin also can obtain or make by common synthetic technology, microbial technique and the animal and plant cells of this area are synthetic by commercial sources.Be used to separate or the chemicals of synthetic wild-scutellaglucone of the present invention, scutellarin or baicalin comprises solvent, reagent, catalyst, blocking group reagent, removes blocking group reagent.Described separation can also comprise adding or remove suitable blocking group finally to obtain the step of required wild-scutellaglucone, scutellarin or baicalin with synthetic.The synthetic chemistry that is used to prepare wild-scutellaglucone of the present invention, 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 that is suitable for includes but not limited to: 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 all can be used for promoting the drug delivery of pharmaceutical composition of the present invention through hydroxyalkyl cyclodextrin such as the derivant of chemical modification such as 2-and 3-HP-or other soluble derivatives etc.
The effective range of wild-scutellaglucone of the present invention and scutellarin or baicalin synergistic effect (molar concentration rate) is verified by suitable in vitro tests (in vitro assay).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, be 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 2.5 | 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 | ||
| 1∶1 | 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±2.9 | 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 2.5 | 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±2.8 | 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±2.5 | ||
| 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 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.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 | Dosage mg/kg | The administration schedule | The rate of losing weight % | Heavy (g) the mean value SD of tumor, | Tumour inhibiting rate % | Number of animals (only) beginning/end |
| Matched group | - | ＜0 | 2.28±0.08 | 10/10 | ||
| Wild yellow unit | 30 | Abdominal cavity 1-10 | ＜5 | 1.71±0.09 | 25 | 10/10 |
| Wild yellow glycoside | 25 | Abdominal cavity 1-10 | ＜5 | 1.81±0.102 | 20.6 | 10/10 |
| Wild yellow glycoside | 50 | Abdominal cavity 1-10 | ＜5 | 1.725±0.12 | 24.3 | 10/10 |
| Wild yellow glycoside | 100 | Abdominal cavity 1-10 | ＜5 | 1.59±0.11 | 34.2 | 10/10 |
| Wild yellow glycoside | 200 | Abdominal cavity 1-10 | ＜5 | 1.451±0.106 | 36.36 | 10/10 |
| Wild yellow unit+wild yellow glycoside | 30+25 | Each abdominal cavity 1-10 | ＜5 | 1.65±0.08 | 27.6 *# | 10/10 |
| Wild yellow unit+wild yellow glycoside | 30+50 | Each abdominal cavity 1-10 | ＜5 | 1.525±0.12 | 33.1 **# | 10/10 |
| Wild yellow unit+wild yellow glycoside | 30+100 | Each abdominal cavity 1-10 | ＜5 | 1.15±0.09 | 49.55 **# | 10/10 |
| Wild yellow unit+wild yellow glycoside | 30+200 | Each abdominal cavity 1-10 | ＜5 | 0.98±0.12 | 57 **# | 10/10 |
| 5-fluorouracil | 10 | Subcutaneous 1-10 | ＜5 | 1.39±0.1 | 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 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 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 | Dosage mg/kg | The administration schedule | The average survival time number of days mean value SD | ILS(％) |
| Matched group | - | 10.2±1.23 | ||
| Wild yellow unit | 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 |
| Wild yellow unit+wild yellow glycoside | 30+25 | Each abdominal cavity 1-10 | 14.85±1.9 | 45.6 *# |
| Wild yellow unit+wild yellow glycoside | 30+50 | Each abdominal cavity 1-10 | 16.25±2.7 | 59 **# |
| Wild yellow unit+wild yellow glycoside | 30+100 | Each abdominal cavity 1-10 | 19.2±2.57 | 88.2 ***# |
| Wild yellow unit+wild yellow glycoside | 30+200 | Each abdominal cavity 1-10 | 21.9±2.1 | 114.7 ***# |
| Cytosine arabinoside (positive controls) | 10 | Abdominal cavity 1-5 | 18.2±2.5 | 78 |
Wild yellow unit=wild-scutellaglucone, wild yellow glycoside=scutellarin
*P＜0.5 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 | Dosage mg/kg | The administration schedule | The rate of losing weight % | Heavy (g) the mean value SD of tumor, | Tumour inhibiting rate % | Number of animals (only) beginning/end |
| Matched group | - | ＜0 | 2.28±0.08 | 10/10 | ||
| Wild yellow unit | 30 | Abdominal cavity 1-10 | ＜5 | 1.71±0.09 | 25 | 10/10 |
| Yellow glycoside | 25 | Abdominal cavity 1-10 | ＜5 | 1.81±0.1 | 20.6 | 10/10 |
| Yellow glycoside | 50 | Abdominal cavity 1-10 | ＜5 | 1.77±0.10 | 22.36 | 10/10 |
| Yellow glycoside | 100 | Abdominal cavity 1-10 | ＜5 | 1.525±0.14 | 33.1 | 10/10 |
| Yellow glycoside | 200 | Abdominal cavity 1-10 | ＜5 | 1.458±0.08 | 30.4 | 10/10 |
| Wild yellow unit+yellow glycoside | 30+25 | Each abdominal cavity 1-10 | ＜5 | 1.62±0.1 | 29 *# | 10/10 |
| Wild yellow unit+yellow glycoside | 30+50 | Each abdominal cavity 1-10 | ＜5 | 1.586±0.08 | 30.4 **# | 10/10 |
| Wild yellow unit+yellow glycoside | 30+100 | Each abdominal cavity 1-10 | ＜5 | 1.141±0.09 | 50 **# | 10/10 |
| Wild yellow unit+yellow glycoside | 30+200 | Each abdominal cavity 1-10 | ＜5 | 0.982±0.128 | 57 **# | 10/10 |
| 5-fluorouracil | 10 | Subcutaneous 1-10 | ＜5 | 1.35±0.1 | 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 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.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 12
Table 12
| Grouping | Dosage mg/kg | The administration schedule | The average survival time number of days mean value SD | ILS(％) |
| Matched group | - | 10.2±1.23 | ||
| Wild yellow unit | 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 |
| Wild yellow unit+yellow glycoside | 30+25 | Each abdominal cavity 1-10 | 14.7±1.9 | 44.1 *# |
| Wild yellow unit+yellow glycoside | 30+50 | Each abdominal cavity 1-10 | 17.35±2.38 | 70.1 **# |
| Wild yellow unit+yellow glycoside | 30+100 | Each abdominal cavity 1-10 | 18.65±2.69 | 82.8 **# |
| Wild yellow unit+yellow glycoside | 30+200 | Each abdominal cavity 1-10 | 22±3 | 115.7 **# |
| Cytosine arabinoside (positive controls) | 10 | Abdominal cavity 1-5 | 18.2±2.5 | 78 |
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.
Wild-scutellaglucone and baicalin are at l: near the zone 0.5～1: 4 concentration ratios 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.
2. the purposes of claim 1, wherein said tumor is that entity tumor or blood are tumor.
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.
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| CN116162077A (en) * | 2023-02-28 | 2023-05-26 | 苏州普瑞森生物科技有限公司 | A kind of baicalein derivative and its preparation method and application |
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| CN116162077A (en) * | 2023-02-28 | 2023-05-26 | 苏州普瑞森生物科技有限公司 | A kind of baicalein derivative and its preparation method and application |
| CN116162077B (en) * | 2023-02-28 | 2024-02-02 | 苏州普瑞森生物科技有限公司 | Baicalein derivative and preparation method and application thereof |
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