CN105582007A - Novel application of osthole in preparation of echinococcosis treating drug - Google Patents
Novel application of osthole in preparation of echinococcosis treating drug Download PDFInfo
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- CN105582007A CN105582007A CN201610045091.XA CN201610045091A CN105582007A CN 105582007 A CN105582007 A CN 105582007A CN 201610045091 A CN201610045091 A CN 201610045091A CN 105582007 A CN105582007 A CN 105582007A
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- osthole
- echinococcosis
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- treating drug
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
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- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a novel application of osthole in preparation of an echinococcosis treating drug. The novel application of the osthole in the preparation of the echinococcosis treating drug has the benefits that the application effect of the osthole on the echinococcosis resistance is disclosed for the first time, the application of the osthole is expanded, and one novel echinococcosis treating drug is developed. A cytotoxicity test, an in-vitro echinococcosis protoscolices killing test, an in-vivo hydatid tissue mass growth inhibition test and a drug in-vivo liver and kidney injury test research prove that the osthole has remarkable echinococcosis protoscolices killing effect, can remarkably inhibit growth of hydatid tissue, does not have obvious cytotoxicity when the osthole is in effective concentration and has no influence on liver and kidney functions of a mouse when the osthole is in the effective concentration.
Description
Technical field
The present invention relates to the new purposes technical field of Chinese herbal medicine, be specifically related to the new purposes of Osthole in the medicine for the preparation for the treatment of echinococcosis.
Background technology
Echinococcosis is to parasitize human body or host animal and the serious parasitic disease that causes by echinococcus. And China is the echinococcosis district occurred frequently that simultaneously has two types of capsule type and blisters. Clinical practice at present the most anti-treating echinococcosis is albendazole, but the intestinal absorption rate of this medicine is very poor, and it generally can only suppress parasite growth and can not thoroughly effectively kill parasite, cause patient must take in a large number for a long time this medicine and just can reach result for the treatment of. Meanwhile, a large amount of research finds that this medicine can cause the serious adverse drug reaction of multisystem. Therefore, finding or develop echinococcosis treatment novel drugs evident in efficacy and that side effect is little is significant.
Cnidium Monnieri is all on the books in medical science works in ancient times, and mainly in order to control, sore tinea scabies, scrotum are wet itches and tonifying kidney and strengthening yang etc. Osthole (Osthole) is the compound that separation and purification obtains from the fruit-frutus cnidii of Umbelliferae annual herb plant cnidium monnieri. Molecular formula is C15H16O3, molecular weight is 244.29, its structural formula is suc as formula shown in (I). This material is dissolved in aqueous slkali, methyl alcohol, ethanol, chloroform, acetone, ethyl acetate and the benzinum etc. that boils, water insoluble and benzinum, mp.83 DEG C～84 DEG C, bp.145 DEG C～150 DEG C. But have no the report that is used for the treatment of echinococcosis with frutus cnidii.
Formula (I)
Summary of the invention
Object of the present invention is exactly for above-mentioned defect of the prior art, provides Chinese herbal medicine common cnidium fruit P.E-Osthole in the new purposes in the medicine for the preparation for the treatment of echinococcosis.
To achieve these goals, technical scheme provided by the invention is: the new purposes of Osthole in the medicine for the preparation for the treatment of echinococcosis.
Further, above-mentioned new purposes, is by Osthole and any one auxiliary material pharmaceutically allowing is made pharmaceutical composition, or makes pharmaceutical composition with other anti-treating echinococcosis.
Further, above-mentioned new purposes, described pharmaceutical dosage form is pharmaceutically acceptable any one formulation, comprises tablet, granule, capsule, pill, oral liquid, injection or liposome.
For Echinococcus Granulosus Cysts, can utilize the external mode of killing Echinococcus Granulosus Cysts protoscolex of Osthole to suppress its activity.
For many rooms echinococcosis tissue, can utilize the mode that suppresses the growth of tissue block in Osthole body to suppress its activity.
Beneficial effect of the present invention is: the new purposes of Osthole provided by the invention in the medicine for the preparation for the treatment of echinococcosis, the effect of Osthole in anti-echinococcosis application disclosed first, expand the application of Osthole, developed a kind of medicine of new treatment echinococcosis simultaneously. The present invention suppresses lesions of liver and kidney experimental study in Hydatid tissues piece growth experiment and medicine body by cytotoxicity experiment, external killing in the experiment of echinococcus protoscolex, body, show that Osthole has the effect of killing significantly echinococcus protoscolex, can suppress significantly the growth of echinococcus tissue, in effective concentration, without obvious cytotoxicity, in effective concentration, the hepatic and renal function of mouse is not affected.
Brief description of the drawings
Fig. 1 is the affect result schematic diagram of Osthole on Echinococcus Granulosus Cysts.
Wherein, viability refers to the survival rate of protoscolex, and Days refers to number of days, and DMSO is dimethyl sulfoxide (DMSO).
Fig. 2 is the affect result schematic diagram of Osthole on Hydatid tissues in Mice Body.
Wherein, control: control group, ABZ: albendazole processed group, osthole: Osthole processed group, parasiteweight: parasite weight in wet base.
Fig. 3 is the affect result schematic diagram of Osthole on cell.
Wherein, cellviability: cell survival rate, ostholeconcentration: Osthole concentration, Changlivercell CCL 13, HePG-2 HCC.
Fig. 4 is the affect result schematic diagram of Osthole on Mouse Liver renal function.
Wherein, Testindexes: test index, Control: control group, ABZ: albendazole processed group, Osthole: Osthole processed group, Totalbilirubin (TBIL) total bilirubin, Directbilirubin (DBIL) bilirubin direct, Indirectbilirubin (IBIL) indirect bilirubin, TP (TotalProtein) total protein, ALB (Albumin) albumin, GLB (Globulin) globulin, ALP (Alkalinephosphatase) alkaline phosphatase, ALT (Alanineaminotransferase) glutamic-pyruvic transaminase, AST (Aspartateaminotransferase) glutamic-oxalacetic transaminease, UREA urea, CREA creatinine.
Detailed description of the invention
Experiment material:
Osthole, purity > 98%, (purchased from Chinese institute for drug control), with the dissolving of DMSO solution, is made into stoste and stores, and then filters with the filter of 0.22 μ m, is placed in-20 DEG C of preservations. When experiment, be diluted to desired concn with sterilized water.
Embodiment 1:
The impact of Osthole on Echinococcus Granulosus Cysts:
Object and principle: observe in vitro the survival rate after protoscolex drug-treated by trypan blue staining, can observe the action effect of medicine to Echinococcus Granulosus Cysts. Normal living cells, after birth structural integrity, can repel trypan blue, makes it can not enter in born of the same parents; And the incomplete cell of loss of activity or cell membrane, the permeability of after birth increases, and can be dyed blueness by trypan blue. It has been generally acknowledged that cell membrane integrity forfeiture, can think dead.
Method: add cleaned Echinococcus Granulosus Cysts protoscolex in 24 orifice plates, control group and dosing group are set, control group adds solvent, and dosing group adds the Osthole containing variable concentrations, Continuous Observation 7 days, with Trypan Blue, records the survival rate of protoscolex.
Calculate protoscolex survival rate according to following formula: survival rate=(the total procephalon joint number of experimental group procephalon joint number/experimental group alive) × 100%.
Result and evaluation: as shown in Figure 1, compared with control group, after Osthole effect, the survival rate of protoscolex obviously declines, illustrate the energy-conservation Echinococcus Granulosus Cysts protoscolex that effectively kills of procephalon.
Embodiment 2:
The effect of Osthole to anti-Echinococcus hydatid cyst in Mice Body:
Object and principle: observe anti-Echinococcus hydatid cyst effect in the body of medicine by taking the method for the weight in wet base of Hydatid tissues piece before and after administration.
Method: 15 every day gastric infusion 100mg/kg, after administration 6 weeks, weigh the weight of tissue block. Balb/c female mice inoculation Hydatid tissues, after 3 months, is divided into three groups: blank group, positive control albendazole group, experimental group Osthole group. Every group five,
Result and evaluation: as shown in Figure 2, compared with control group, after Osthole effect, the weight in wet base of tissue block obviously declines, illustrate that Osthole has anti-Echinococcus hydatid cyst effect in good body.
Embodiment 3:
The impact of Osthole on cell:
Object and principle: cytotoxicity experiment adopts MTTassay. MTTassay is a kind of assay method that uses colorimetric method indirectly to measure living cells quantity. Detection principle is that the succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to water-insoluble bluish violet Jie Jing Jia Za and be deposited in cell, and dead cell is without this function. Jia Za in dimethyl sulfoxide (DMSO) energy dissolved cell, measures its absorbance value with ELIASA at 490nm wavelength place, and within the scope of certain cell number, the amount that MTT crystallization forms is directly proportional to cell number.
Method: add HePG-2 and people's CCL 13 in 96 orifice plates, control group and dosing group are set, control group adds solvent, dosing group adds the Osthole containing variable concentrations, hatches after 48 hours, adds MTT, hatch 4 hours, detect absorbance value with ELIASA at 490nm place.
Result and evaluation: as shown in Figure 3, compared with control group, the propagation of HePG-2 and people's CCL 13 is not subject to obvious inhibition, illustrate in the valid density that echinococcus is had to fragmentation effect Osthole to cell without overt toxicity.
Embodiment 4:
The schematic diagram of the impact of Osthole on Mouse Liver renal function:
Object and principle: by the biochemical indicator of hepatic and renal function being verified to the toxicity of Osthole. Hepatic and renal function inspection is by the various biochemical test method monitoring indices relevant with hepatic and renal function metabolism, to reflect the function basal conditions of liver.
Method: 9 Balb/c female mices are divided into three groups: blank group, positive control albendazole group, experimental group Osthole group. Every group 3, every day gastric infusion 100mg/kg, administration is after 6 weeks, eyeball blood sampling, separates supernatant, test liver kidney biochemical indicator.
Result and evaluation: as shown in Figure 4, compared with control group, Osthole group and albendazole group all do not have conspicuousness to change, and prove that Osthole does not affect hepatic and renal function in valid density.
Finally it should be noted that: the foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, although the present invention is had been described in detail with reference to previous embodiment, for a person skilled in the art, its technical scheme that still can record aforementioned each embodiment is modified, or part technical characterictic is wherein equal to replacement. Within the spirit and principles in the present invention all, any amendment of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (3)
1. the new purposes of Osthole in the medicine for the preparation for the treatment of echinococcosis.
2. new purposes according to claim 1, is characterized in that, is any one auxiliary material of Osthole and pharmaceutically permission is made to pharmaceutical composition, or makes pharmaceutical composition with other anti-treating echinococcosis.
3. new purposes according to claim 1, is characterized in that, described pharmaceutical dosage form is pharmaceutically acceptable any one formulation, comprises tablet, granule, capsule, pill, oral liquid, injection or liposome.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610045091.XA CN105582007B (en) | 2016-01-22 | 2016-01-22 | Purposes of the Osthole in the drug for treating echinococcosis is prepared |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610045091.XA CN105582007B (en) | 2016-01-22 | 2016-01-22 | Purposes of the Osthole in the drug for treating echinococcosis is prepared |
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| Publication Number | Publication Date |
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| CN105582007A true CN105582007A (en) | 2016-05-18 |
| CN105582007B CN105582007B (en) | 2018-06-01 |
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| CN201610045091.XA Expired - Fee Related CN105582007B (en) | 2016-01-22 | 2016-01-22 | Purposes of the Osthole in the drug for treating echinococcosis is prepared |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107982264A (en) * | 2017-11-24 | 2018-05-04 | 武汉市农业科学院 | A kind of drug regimen for preventing animal echinococcosis and its application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1205215A (en) * | 1997-07-10 | 1999-01-20 | 张富永 | Parasitosis eliminating powder |
| CN1371708A (en) * | 2001-05-18 | 2002-10-02 | 蒋次鹏 | Medicine coposition for treating hydatid disease |
| CN104840613A (en) * | 2015-06-16 | 2015-08-19 | 段占娥 | Medicine composition for treating primary alveolar hydatid disease as well as preparation method and application thereof |
-
2016
- 2016-01-22 CN CN201610045091.XA patent/CN105582007B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1205215A (en) * | 1997-07-10 | 1999-01-20 | 张富永 | Parasitosis eliminating powder |
| CN1371708A (en) * | 2001-05-18 | 2002-10-02 | 蒋次鹏 | Medicine coposition for treating hydatid disease |
| CN104840613A (en) * | 2015-06-16 | 2015-08-19 | 段占娥 | Medicine composition for treating primary alveolar hydatid disease as well as preparation method and application thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107982264A (en) * | 2017-11-24 | 2018-05-04 | 武汉市农业科学院 | A kind of drug regimen for preventing animal echinococcosis and its application |
| CN107982264B (en) * | 2017-11-24 | 2020-03-20 | 武汉市农业科学院 | Pharmaceutical composition for preventing and treating animal echinococcosis and application thereof |
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| Publication number | Publication date |
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| CN105582007B (en) | 2018-06-01 |
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Granted publication date: 20180601 Termination date: 20190122 |