CN101829199B - Application of ranunculus japonicus extract in preparing anti-tumor and anti-tumor angiogenesis drugs - Google Patents
Application of ranunculus japonicus extract in preparing anti-tumor and anti-tumor angiogenesis drugs Download PDFInfo
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- CN101829199B CN101829199B CN2010101685455A CN201010168545A CN101829199B CN 101829199 B CN101829199 B CN 101829199B CN 2010101685455 A CN2010101685455 A CN 2010101685455A CN 201010168545 A CN201010168545 A CN 201010168545A CN 101829199 B CN101829199 B CN 101829199B
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Abstract
The invention discloses the application of ranunculus japonicus extract in preparing drugs, health food or cosmetics for inhibiting angiogenesis. The invention discovers that the ranunculus japonicus extract has activity for inhibiting tumor and tumor angiogenesis for the first time, and the drugs for inhibiting tumor and tumor angiogenesis, which are prepared by utilizing the discovery, can be used for treating or preventing diseases related to tumors or tumor angiogenesis or for tumor chemotherapy and/or adjuvant chemotherapy. The invention skillfully takes the angiogenesis as a target point for treating diseases, studies and clarifies the medical treatment effects and mechanism of the ranunculus japonicus extract, provides scientific foundation and important information for the development of new application and for discovering new target points of the drug effects, and is a novel development direction of traditional Chinese medical theories.
Description
Technical field
The present invention relates to a kind of Herba Ranunculi Japonici extract and suppress the medicine of angiogenesis or the application in health food or the cosmetics in preparation.
Background technology
Blood vessel is essential with the function maintenance by the form generation of normal structure organ, and it is closely related with all diseases that human development's imbalance and Different types of etiopathogenises cause.Malignant tumor is the arch-criminal of present China people's life health, also is country's " Population and Health " scientific and technological key research projects.The tumor neovascularization tumorigenesis, transfer and recurrence play a part very important.A series of studies show that as long as effectively suppress the tumor neovascularization or destroy existing tumor vessel just can be suppressed tumor and be generated, shift and recurrence.In addition, the diseases such as diabetes and rheumatic arthritis have blood vessel hyperplasia, and its aberrant angiogenesis and tumor vessel are closely similar.Therefore, angiogenic inhibitor also can be used for treating the vascular proliferative diseases such as diabetes and rheumatic arthritis.
In recent years, people deepen continuously to the research of tumor-blood-vessel growth mechanism, and medicine such as Avastin, Angiostatin etc. that many antineoplastic vasculars generate are developed in succession, apply clinically.This class medicine not only can be used for the treatment of most of entity tumors, can also be used for the prevention of tumor and the treatment of Malignancy, to prevention and the treatment of the disease of other and associated angiogenesis such as diabetic renal papillary necrosis, rheumatic arthritis, psoriasis, hemangioma, atherosclerosis etc., all have certain theory and realistic meaning simultaneously.
Herba Ranunculi Japonici is the Herb of Ranunculaceae (Ranunculaceae) Ranunculus (Ranunculus) Herba Ranunculi Japonici, property suffering, little hardship, temperature, energy dampness removing, detumescence, pain relieving, nebula removing, preventing the attack (or recurrence) of malaria, parasite killing are used for stomachache, jaundice, malaria, tuberculous lymphadenitis, pterygium, corneal nebula, the maggot of going out, infanticide Jue.Herba Ranunculi Japonici originates in all parts of the country, is born in field, roadside, limes marginis, the hillside weeds clump; There is distribution in northeast to south China.Through the document investigation, have no Chinese scholar suppresses angiogenesis function to Herba Ranunculi Japonici extract pertinent literature report.
Summary of the invention
The object of the invention is to provide a kind of Herba Ranunculi Japonici extract to suppress the medicine of angiogenesis or the application in health food or the cosmetics in preparation, a kind of scheme of preventing and treating of new inhibition angiogenesis is provided, for finding that the new target spot of drug effect provides scientific basis and important information, for Chinese medical theory provides new developing direction.
In order to solve these problems of the prior art, technical scheme provided by the invention is:
A kind of Herba Ranunculi Japonici extract suppresses the medicine of angiogenesis or the application in health food or the cosmetics in preparation.
Preferably, contain pharmaceutically Herba Ranunculi Japonici extract and the pharmaceutically acceptable carrier thereof of effective dose in the medicine of described inhibition angiogenesis.
Preferably, the pharmaceutical dosage form of described inhibition angiogenesis is selected from injection, tablet, powder, granule, capsule, oral agents, unguentum, cream or Emulsion.
Preferably, the medicine of described inhibition angiogenesis is used for preventing and treating at least a disease that is selected from one of the following: hemangioma, fibrohemangioma, leukemia, neovascular glaucoma, diabetic renal papillary necrosis, retinopathy of prematurity and retinal vein occlusion, retinal degeneration, retrolental fibroplasia, trachomatous conjunctivitis, the keratopathy that angiogenesis causes, climacteric macula lutea and degeneration of macula, psoriasis, the degeneration of old plate-like speckle, rheumatic arthritis, psoriasis, telangiectasis, botryomycosis hominis, suppressing spot in the wound healing forms, atherosclerosis, seborrheic dermatitis and acne.
Preferably, the medicine of described inhibition angiogenesis is used for chemotherapy or the auxiliary treatment of tumor or neoplasm metastasis.
The invention provides the Chinese medicine extract of the preparation take Herba Ranunculi Japonici as raw material, wherein contain the active component of multiple inhibition tumor and tumor-blood-vessel growth effect.
Herba Ranunculi Japonici extract for suppressing tumor and tumor-blood-vessel growth of the present invention, its preparation method is the dry seed that water or organic solvent or water-containing organic solvent extract Herba Ranunculi Japonici, and extracting liquid filtering, concentrated, drying are formed.The Herba Ranunculi Japonici extract that the inhibition tumor of described Herba Ranunculi Japonici extract preparation and tumor-blood-vessel growth medicine contain effective dose and routine will be used carrier and or excipient.Can be made into injection, tablet, powder, granule, capsule, oral agents, unguentum, cream or Emulsion.
Extract of the present invention be used for control and or treat the disease that is selected from one of the following more than at least a:: cancer and or cancer metastasis, hemangioma, fibrohemangioma, neovascular glaucoma, diabetic renal papillary necrosis, retinopathy of prematurity and retinal vein occlusion, retinal degeneration, retrolental fibroplasia, trachomatous conjunctivitis, the keratopathy that angiogenesis causes, climacteric macula lutea and degeneration of macula, psoriasis, the degeneration of old plate-like speckle and rheumatic arthritis, psoriasis, telangiectasis, botryomycosis hominis suppresses spot and forms in the wound healing, atherosclerosis, seborrheic dermatitis and acne.
Extract of the present invention has the purposes of antitumor, tumor-blood-vessel growth and other and associated angiogenesis disease treatment, prevention.Certainly, extract also is useful on the purposes of chemotherapy of tumors and/or auxiliary treatment.Extract of the present invention can prepare and suppress tumor and tumor-blood-vessel growth health food or cosmetics.
Herba Ranunculi Japonici extract can prepare with conventional method among the present invention.In actual needs, in Herba Ranunculi Japonici extract, can add one or more pharmaceutically acceptable carriers.Described carrier comprises the diluent of pharmaceutical field routine, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption carrier, lubricant, emulsifying agent, osmotic pressure regulator can also add flavouring agent, sweeting agent etc. in case of necessity.
The preparation process that Herba Ranunculi Japonici extract can be routinely among the present invention, use separately or prepare the clinically medicine of operable various different dosage forms that causes disaster, various ways such as injection, tablet, powder, granule, capsule, oral agents, unguentum, cream or Emulsion with other drug.
Herba Ranunculi Japonici extract can be applied to antitumor, tumor-blood-vessel growth and other and associated angiogenesis disease treatment, prevention among the present invention, can also be used for chemotherapy of tumors and/or adjuvant chemotherapy.More specifically, the invention provides extract for the inhibition angiogenesis of medicine, food, cosmetics.
With respect to scheme of the prior art, advantage of the present invention is:
The present invention finds that first Herba Ranunculi Japonici extract has the activity that suppresses tumor and tumor-blood-vessel growth, the disease that the medicine that utilizes this discovery preparation to suppress tumor and tumor-blood-vessel growth can be used for treating or prevention is relevant with tumor or tumor-blood-vessel growth also can be used for the treatment of chemotherapy of tumors and/or adjuvant chemotherapy aspect.The present invention is dexterously with the target spot of angiogenesis as the treatment disease, research is also illustrated medicinal curative effect and the mechanism of Herba Ranunculi Japonici extract, developing and find that for its new purposes the new target spot of drug effect provides scientific basis and important information, is the new developing direction of Chinese medical theory.This Herba Ranunculi Japonici extract can be used for medicine, health product and or the purposes such as cosmetics.
Description of drawings
The invention will be further described below in conjunction with drawings and Examples:
Fig. 1: Herba Ranunculi Japonici extract is on the impact (A: Herba Ranunculi Japonici water extract of tumor cell in vitro class angiogenesis; B: the Herba Ranunculi Japonici ethanol extract)
Fig. 2: Herba Ranunculi Japonici extract is on the impact (C: Herba Ranunculi Japonici ether extract of tumor cell in vitro class angiogenesis; D: the Herba Ranunculi Japonici chloroform extract);
Fig. 3: Herba Ranunculi Japonici extract is on the impact (E: Herba Ranunculi Japonici ethyl acetate extract of tumor cell in vitro class angiogenesis; F: the Herba Ranunculi Japonici n-butanol extract);
Fig. 4: Herba Ranunculi Japonici extract is on the impact (G: Herba Ranunculi Japonici total glycosides) of tumor cell in vitro class angiogenesis;
Fig. 5: Herba Ranunculi Japonici extract D is on the impact of tumor cell in vitro class angiogenesis;
Fig. 6: Herba Ranunculi Japonici extract D1 is on the impact of tumor cell in vitro class angiogenesis;
Fig. 7: Herba Ranunculi Japonici extract D2 is on the impact of tumor cell in vitro class angiogenesis;
Fig. 8: Herba Ranunculi Japonici extract D3 is on the impact of tumor cell in vitro class angiogenesis;
Fig. 9: Herba Ranunculi Japonici extract D4 is on the impact of tumor cell in vitro class angiogenesis;
Figure 10: Herba Ranunculi Japonici extract E is on the impact of tumor cell in vitro class angiogenesis;
Figure 11: Herba Ranunculi Japonici extract E1 is on the impact of tumor cell in vitro class angiogenesis;
Figure 12: Herba Ranunculi Japonici extract E2 is on the impact of tumor cell in vitro class angiogenesis;
Figure 13: Herba Ranunculi Japonici extract G is on the impact of tumor cell in vitro class angiogenesis;
Figure 14: Herba Ranunculi Japonici extract G1 is on the impact of tumor cell in vitro class angiogenesis;
Figure 15: Herba Ranunculi Japonici extract G2 is on the impact of tumor cell in vitro class angiogenesis;
Figure 16: Herba Ranunculi Japonici extract G3 is on the impact of tumor cell in vitro class angiogenesis;
Figure 17: Herba Ranunculi Japonici extract G4 is on the impact of tumor cell in vitro class angiogenesis;
Figure 18: Herba Ranunculi Japonici extract G is on the impact of external Matrigel tumor cell 3B11 class angiogenesis;
Figure 19: Herba Ranunculi Japonici extract G is on the impact of external Matrigel tumor cell SW872 class angiogenesis;
Wherein Control is the blank group; The positive matched group of Fu; A represents the Herba Ranunculi Japonici water extract, B represents the Herba Ranunculi Japonici ethanol extract, C represents the Herba Ranunculi Japonici ether extract, D represents the Herba Ranunculi Japonici chloroform extract, E represents the Herba Ranunculi Japonici ethyl acetate extract, and F represents the Herba Ranunculi Japonici n-butanol extract, and G represents Herba Ranunculi Japonici total glycosides, be provided with the comparative result of the variable concentrations such as 1ug/mL, 10ug/mL, 100ug/mL, 1000ug/mL (or 250ug/mL, or 500ug/mL).
The specific embodiment
Below in conjunction with specific embodiment such scheme is described further.Should be understood that these embodiment are not limited to limit the scope of the invention for explanation the present invention.The implementation condition that adopts among the embodiment can be done further adjustment according to the condition of concrete producer, and not marked implementation condition is generally the condition in the normal experiment.Herba Ranunculi Japonici extract provided by the invention is provided by Suzhou Chinese Herbal Medicine Inst.
Embodiment 1: Herba Ranunculi Japonici extract is to the inhibitory action of external tumor-blood-vessel growth
Place the DMEM culture fluid that contains 10% hyclone in 37 ℃, 5%CO mice liposarcoma cell SW872
2Incubator is cultivated.The trophophase cell of taking the logarithm is with 4*10
4/ mL cell kind is put in 37 ℃, 5%CO in being covered with in advance fibrinous 24 orifice plates of one deck
2Incubator was cultivated 24 hours.Behind the 24h, add variable concentrations (1-1000ug/mL) Herba Ranunculi Japonici extract, take blank culture fluid as contrast, with the positive contrast of 5uM 5-Fu, behind the cultivation 36h, carefully remove supernatant, dye with the Wright-Gimsa dye liquor, choose afterwards every hole representative region and take pictures.Above-mentioned experiment repeats 3 times.
The result is shown in Fig. 1 to 17, and multiple Herba Ranunculi Japonici extract has good inhibitory action to the external class angiogenesis of tumor cell.
Embodiment 2: Herba Ranunculi Japonici extract is to the inhibitory action of kinds of tumor cells propagation
Place the DMEM that contains 10% hyclone or RPMI RPMI-1640 in 37 ℃, 5% CO tumor cell line 2C4G2, U937,2C4, Dami, Namalva, K562, PMKO102-3#, BAEC, HMY2-CIR
2Incubator is cultivated.The trophophase cell of taking the logarithm in 96 orifice plates, wherein carries out administration when suspension cell kind plate with the cell kind of suitable concn, carries out administration behind the attached cell 24h.Be put in 37 ℃, 5% CO
2Incubator was cultivated 24 hours.Behind the 24h, attached cell adds variable concentrations (1-400ug/mL) Herba Ranunculi Japonici extract, take the blank culture fluid that adds cell as contrast, take the blank culture fluid that do not add cell as blank, cultivate 46h after, add Alamar blue reagent 10uL/ hole, being put in 37 ℃, 5% CO2 incubator cultivates after 2 hours and carries out drafting board, choose 560nm, 590nm and carry out fluoroscopic examination, obtain basic flat fluorescent (RFU), and calculate suppression ratio.Above-mentioned experiment repeats 3 times.Suppression ratio is calculated as follows:
The result as shown in Table 1 and Table 2, Herba Ranunculi Japonici extract G component has good inhibitory action to kinds of tumor cells system such as the propagation of 2C4G2,2C4, Dami, Namalwa, K562, HMY2-CIR etc.
Table 1 G component is to the exercising result (RFU) of kinds of tumor cells system
Table 2 G component is to the exercising result (suppression ratio) of kinds of tumor cells system
Embodiment 3: Herba Ranunculi Japonici extract is to the inhibitory action of external Matrigel tumor-blood-vessel growth
Get the Matrigel of the BD company of 150uL thawing, join in 48 orifice plates, pat and make it even distribution, hatch 1h for 37 ℃ and make Matrigel aggregate into glue.Take the logarithm tumor cell SW872 and the 3B11 of trophophase are with 4*10
5/ mL cell kind is seeded on the Matrigel with the 200uL/ hole, in 37 ℃, 5% CO in mixing with the RPMI RPMI-1640 equal-volume that contains the variable concentrations Herba Ranunculi Japonici extract
2Incubator was cultivated after some hours, use the dyeing of Wright-Gimsa dye liquor after, place microscopically to observe and take pictures.
Such as Figure 18 and shown in Figure 19, the result shows, Herba Ranunculi Japonici extract G component all has good inhibitory action to the external Matrigel model of two kinds of tumor cells, and is dose dependent.Contrast category blood vessel is thick, and it is clear that tubular structure connects, and after the Herba Ranunculi Japonici extract effect, the tubular structure mould obviously reduces, and is interrupted, breaks up.
The present invention is described in conjunction with most preferred embodiment, yet after having read foregoing of the present invention, those skilled in the art can understand and do many changes in disclosed embodiment and also can obtain same or similar result, and do not exceed design of the present invention, spirit and scope.More particularly, obviously some chemistry and alternative reagent disclosed herein of physiological related reagent and obtain same or similar result.All similarly replace and modify for a person skilled in the art, obviously think all that namely all above-mentioned these equivalent form of values all fall within the application's appended claims limited range equally in spirit of the present invention, scope and design and the claim scope.
Claims (4)
1. the application of Herba Ranunculi Japonici extract in the medicine of preparation inhibition angiogenesis, the medicine of described inhibition angiogenesis is that inhibition tumor cell is the medicine of SW872,3B11,2C4G2,2C4, Namalva, BAEC, HMY2-CIR angiogenesis; Described Herba Ranunculi Japonici extract is Herba Ranunculi Japonici total glycosides.
2. application according to claim 1 is characterized in that containing pharmaceutically Herba Ranunculi Japonici extract and the pharmaceutically acceptable carrier thereof of effective dose in the medicine of described inhibition angiogenesis.
3. application according to claim 1 is characterized in that the pharmaceutical dosage form of described inhibition angiogenesis is selected from injection, tablet, powder, granule, capsule, unguentum, cream or Emulsion.
4. application according to claim 1 is characterized in that the medicine of described inhibition angiogenesis is used for chemotherapy or the auxiliary treatment of tumor or neoplasm metastasis.
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| 张家华等.毛茛甙体外抗白血病细胞的毒性试验.《中国肿瘤临床》.1993,第20卷(第12期),941-942. * |
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Effective date of registration: 20210204 Address after: Room 104, building 7, No.10 Lishe lane, Suzhou, Jiangsu 215000 Patentee after: Jiangsu Big Investment Co.,Ltd. Address before: Yunxuan building, Suzhou University, 199 Ren'ai Road, Suzhou Industrial Park, Jiangsu Province, 215123 Patentee before: Suzhou Institute of Traditional Chinese Medicine |
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