CN104490913A - Application of breviscapine and glycyrrhizic acid in preparation of medicine for preventing and treating ionizing radiation injury - Google Patents
Application of breviscapine and glycyrrhizic acid in preparation of medicine for preventing and treating ionizing radiation injury Download PDFInfo
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- CN104490913A CN104490913A CN201410858049.0A CN201410858049A CN104490913A CN 104490913 A CN104490913 A CN 104490913A CN 201410858049 A CN201410858049 A CN 201410858049A CN 104490913 A CN104490913 A CN 104490913A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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Abstract
The invention relates to the field of medicines, relates to application of breviscapine and glycyrrhizic acid in preparation of a medicine for preventing and treating ionizing radiation injury, and discloses application of breviscapine which is a flavonoid effective ingredient extracted from plant Erigeronbrevisca-pus and has a chemical name of 4,5,6, trihydroxy ketone-7-glucuronide and glycyrrhizic acid which is a saponin ingredient (artificial synthesis available) extracted from plant licorice root and has an English name of Glycyrrhizin in preparation of a medicine for preventing and treating ionizing radiation injury. The two active ingredients have the radiation protecting effect in cellular level and animal living level, have a protective effect in wide dosage ranges of lethal dose, sub-lethal dose and low dose radiation, have the advantages of stable quality, low cost and wide source, and can be used for preparing a medicine for preventing and treating related injury rescue and diseases caused by ionizing radiation injury.
Description
Relate to field
The present invention relates to field of medicaments, specifically be to extract and next flavonoids effective constituent breviscapine from plant Herba Erigerontis Erigeronbrevisca-pus, chemistry by name 4,5,6, trihydroxy ketone-7-glucuronide and a kind of saponin component extracting from liquorice root and come or can by the glycyrrhizic acid of synthetic, the application of English name Glycyrrhizin in the associated injury treatment caused for the preparation of prevention and therapy ionizing radiation and disease treatment.
Background technology
Flourish along with global core cause, nuclear technology is in every field extensive uses such as nuclear power station, aerospace industry, national defence and biological medicines, human contact's ionizing radiation also causes the chance damaged to increase, the nuclear war simultaneously brought along with world's nuclear safety situation is nervous and nuclear terrorism secret worry, the protection of the body injury (referred to as radiation damage) that ionizing radiation causes is being subject to increasing attention with treatment.
On the other hand, the sickness rate of malignant tumor and patient populations are in recent years always in the trend continuing to rise, radiotherapy is as one of essential therapeutic arsenals, play a part indispensable, but high dose radiation irradiates the acute radiation injury of tumor surrounding normal tissue and organ and even the whole body that can cause unavoidably, the side reaction that radiation damage brings seriously limits the extensive use of radiotherapy in oncotherapy, also obviously have impact on the quality of life after tumor patient Radiotherapy and treatment.
The radiation damage treatment related drugs of putting on market at present mainly contains: sulfur-containing compound, hormones, cytokine class and Chinese herbal medicine etc., there is respective inherent shortcoming in them: the general side effect of such as sulfur-containing compound larger respectively, amifostine (having another name called Amifostine) is the best compound of the protection effect of generally acknowledging at present as the representative of this compounds, it is international managing body pass through first selectively wide spectrum cytoprotective, but half-life extremely short (7 minutes) and expensive (domestic medical market price 400-500 unit /) limit its application, and hormone medicine to the control of radiation damage mainly to bone marrow nucleated cell, hematopoietic stem cell and CFU-GM, the impact of this type of medicine on sexual organ and reproductive system limits widely using of it, the hemopoietic function of bone marrow system injury that radiation causes can be alleviated and give treatment to cytokine class medicine such as interleukin class, colony stimulating factor class medicine, but its Study On The Radioprotective and administration time closely related (in the medical practice for preventing and give treatment to, this type of medicine requires high to medical care detection level and degree of concern), there is obvious proinflammatory effect, and expensive, be difficult to room temperature and preserve, Chinese herbal medicine class radioprotective composition mainly contains phenols, polysaccharide, natural flavonoid, has the features such as active component is indefinite, low toxicity, studies through for many years, so far without listing or similar drugs to be gone on the market.
The present invention relates to two kinds to extract from natural plants, also can synthetic compound preparing prevention and therapy ionization radiation injury treatment and tumour radiotherapy ancillary drug in application.
Breviscapine is a kind of effective ingredient being extracted from natural plants, and be the flavonoids effective constituent of extraction and isolation from Compositae short stem of a herb platymiscium Herba Erigerontis Erigeronbrevisca-pus whole plants, molecular formula is C
25h
24o
12, molecular weight is 462.21, water soluble, and chemistry 4,5,6, trihydroxy ketone-7-glucuronides by name, have the effect of expansion of cerebral vascular, reduce cerebral vascular resistance, increase cerebral blood flow, improve microcirculation, and have the effect to antiplatelet aggregation.Clinically be used for the treatment of sudden deafness, atherosclerosis obliterans cortical blindness, diabetic peripheral neuropathy, ischemic necrosis of femoral head, rheumatoid arthritis, acquired paralytic strabismus, nephrotic syndrome etc.
Glycyrrhizic acid is a kind of is extracted from natural plants and can the single compound of synthetic in a large number, also known as glycyrrhizin, glycyrrhizin, it is a kind of saponin component be separated from glycyrrhiza uralensis fisch, it is the main component in Radix Glycyrrhizae, also be effective ingredient, be present in glycyrrhizic legume Glycyrrhizinauralensis Fisch. root and rhizome, Glycyrrhiza glabra L. Glycyrrhiza glabraL. root and rhizome, Semen Abri Precatorii Abrus precatoriusL. leaf etc.Radix Glycyrrhizae has multiple pharmacological function and body-care effect, is listed in be food and the health food list of medicine by national health and Family Planning Committee.Glycyrrhizic acid, has another name called glycyrrhizin, English name Glycyrrhizin, Glycyrrhizic acid, molecular formula C
12h
22o
16divide in amount 833.94, CAS 1405-86-3, white is to pale yellow powder, taste is sweet, sugariness is about the 150-200 of sucrose doubly, and sweet taste remaining time is long, soluble in water, be dissolved in Diluted Alcohol, glycerol, propylene glycol, be insoluble to dehydrated alcohol, ether, chloroform and oils and fats, be used as correctives and flavoring agent, with low cost, safety non-toxic in industry and food service industry.This compound is had the fields such as antitumor, treatment cardiovascular and cerebrovascular vessel ischemical reperfusion injury, neurological disease, inflammatory diseases by wide coverage.
Up to now, breviscapine, glycyrrhizic acid, and both compositionss for the preparation of prevention and therapy ionization radiation injury treatment and tumour radiotherapy ancillary drug in application there is not been reported.
Summary of the invention
The object of this invention is to provide the novelty teabag of breviscapine and glycyrrhizic acid composite reagent.
The novelty teabag of breviscapine provided by the present invention and glycyrrhizic acid is: for the preparation of the treatment of prevention and therapy ionization radiation injury and the application of tumour radiotherapy ancillary drug aspect.
Ionization radiation injury of the present invention comprises fatal dose irradiation, sublethal dose and low dose exposure damage, also comprises the radiation damage that tumour radiotherapy produces.
Breviscapine provided by the invention and glycyrrhizic acid type of service, according to clinical needs, can add corresponding adjuvant, exists with dosage forms such as tablet, pill, capsule, suspension, solution, syrup, injection, solvent, cream, ointment, sprays.
The using dosage of breviscapine provided by the present invention and glycyrrhizic acid novelty teabag 1-10g/Kg body weight (people), but is not limited thereto scope, and both preferred proportions are 1: 4 ~ 1: 10, and preferred formulation form is oral+injection.
Objects and advantages of the present invention are by for illustration and explanation by the non-limitative illustration of following preferred embodiments, and these embodiments provide as an example with reference to accompanying drawing.
Accompanying drawing explanation
Fig. 1 breviscapine and glycyrrhizic acid significant prolongation C57 Mus fatal dose irradiate, and (χ roentgenization: Fig. 1 a, gamma-rays irradiates: natural law of Fig. 1 b) surviving afterwards.
Fig. 2 breviscapine and glycyrrhizic acid significantly improve C57 Mus sublethal dose (9Gy gamma-rays) and irradiate latter 30 days survival rates.
Fig. 3 breviscapine and glycyrrhizic acid irradiate the Hemoprotection of the radiation damage caused to low dosage (5Gy gamma-rays).
Fig. 4 breviscapine and glycyrrhizic acid are to the radiate protective action of breast cancer tumor cells (MCF-7 cytological map, 1. matched group under microscope; 2. irradiation group; 3 breviscapine 0.1mg/ml; 4. irradiation+breviscapine 0.1mg/ml; 5. matched group; 6. irradiation group; 7. glycyrrhizic acid 0.1 μM; 8. irradiation+breviscapine glycyrrhizic acid 0.1 μM).
Detailed description of the invention
Embodiment one
Single fatal dose (13Gy χ ray/gamma-rays) irradiates the radiation damage treatment caused
Breviscapine, can prepare voluntarily with reference to published patent of invention description or pertinent literature, also can buy in medical market, administering mode is lumbar injection, and dosage is 3 ~ 6mg/Kg body weight (Mus).
Glycyrrhizic acid, Glycyrrhizin, purchased from TCI company, article No. G0150, lot number 8XM3D-EJ, purity > 93.0%, administering mode is lumbar injection, and dosage is 20 ~ 40mg/Kg body weight.
χ beam exposure apparatus X-Rad RS-2000 irradiation instrument, voltage 160KV, band radiation energy is 50KeV, close rate 1.01Gy/min.
Gamma-rays irradiation unit
137cs irradiation instrument, close rate 0.5Gy/min.
C57BL/6 mice, male and female half and half, body weight 18-20g, quality certification SCXK (capital) 2012-0001, grouping situation is: do not irradiate group, irradiation and to normal saline group, irradiation and to breviscapine group, irradiation and to glycyrrhizic acid group, irradiation and give breviscapine+glycyrrhizic acid group, often organize 10.
Adopt the total irradiation of single fatal dose, single medicine group dosage regimen is pre-irradiation 30 minutes intraperitoneal administrations, supplements immediately and is administered once, within every 24 hours afterwards, be administered once, continuous 14 days after irradiation.Composite reagent group dosage regimen is pre-irradiation 30 minutes intraperitoneal administration breviscapines: glycyrrhizic acid (1: 10,4mg/Kg body weight: 40mg/Kg body weight), administration glycyrrhizic acid (40mg/Kg body weight) is supplemented once immediately after irradiation, according to breviscapine after 8 hours: glycyrrhizic acid (1: 5) administration, then every 24 hours in 1: 5 ratio continue administration, continuous 14 days.
Testing index: survival natural law.
Experimental result is shown in Fig. 1, and breviscapine and glycyrrhizic acid combination medicine-feeding can the postradiation survival natural law of significant prolongation C57 Mus fatal dose, are better than both individually administrations.
Embodiment two
Sublethal dose (9Gy gamma-rays) irradiates the radiation damage treatment caused
Medicine information, animal information, irradiation devices and parameter, administering mode are identical with embodiment one.
Exposure dose is 9Gy.
Testing index: 30 days survival rates.
Experimental result is shown in Fig. 2, and breviscapine and glycyrrhizic acid combination medicine-feeding can significantly improve the survival rate after C57 Mus Sublethal Doses, is better than both individually administrations.
Embodiment three
Low dosage (5Gy gamma-rays) irradiates the Hemoprotection of the radiation damage caused
Medicine information, animal information, irradiation devices and parameter, administering mode are identical with embodiment one.
Exposure dose is 5Gy.
Testing index: body weight, peripheral blood counting, one-sided femur counting, CFU-GM, index and spleen index, thymus index.Experimental result is shown in Fig. 3, and breviscapine and glycyrrhizic acid combination medicine-feeding significantly can show the hemopoietic system damage alleviating the animal that low dose exposure causes.
Embodiment four
Breviscapine, glycyrrhizic acid are to kinds of tumor cells/Normocellular radiate protective action
Medicine information, irradiation devices are identical with embodiment one with parameter.
Cell line adopts MCF-7 Breast Cancer Cell, breast carcinoma MDA-MB-231 cell, hepatoma Hep G 2 cells, lung cancer A549 cell, Human Embryonic Kidney HEK 293 cell, people's microvascular endothelial HMEC-1 cell.
Experimentation:
1. cell line and cultivation
Adopt human hepatoma HepG2 cell, typeⅡ pneumocyte, respectively with containing 10%FBS (Gibico, REF10099-141), containing 100 μ g/ml streptomycins and 100U/ml penicillin, DMEM in high glucose (Hyclone, SH30243.01B) and PRMIl640 (Hyclone, SH30809.01B) cultivate, be placed in 37 DEG C, 5%CO
2constant incubator in routine passage cultivate.
2. drug treating and irradiation
Cell culture, to exponential phase, changes the culture fluid containing variable concentrations medicine, continues cultivation 24 hours, accepts various dose gamma-rays and irradiates.
3. colony formation
After cell irradiation, inoculate different cell quantity by different exposure doses and be inoculated into 60mm culture dish.Cell continuous culture was fixed with methanol after 3 weeks, and add Ji's nurse Sa application liquid and dye 30 minutes, flowing water is cleaned, clone's number of counting cells number >=50.Cloning efficiency and surviving fraction is calculated by cloning efficiency PE=(matched group clone number/experimental group cell number) × 100% and surviving fraction=clone's number/(experimental group cell number × PE).And click models fitting drafting cell survival curve by many targets.
Testing index: IC50 (killing the radiological dose of 50% cell)
Experimental result is shown in Fig. 4 and table 1 ~ 2, and breviscapine and glycyrrhizic acid can improve kinds of tumor cells or Normocellular radiation tolerance dose respectively, have certain radiate protective action.
Table 1 breviscapine irradiates the impact (Gy) of IC50 to kinds of tumor cells/normal cell gamma-rays
Table 2 glycyrrhizic acid irradiates the impact (Gy) of IC50 to kinds of tumor cells/normal cell gamma-rays
Comprehensive above embodiment result, explanation the invention has the advantages that:
Breviscapine and glycyrrhizic acid is individually dosed and combination can both play radiate protective action in cellular level and living animal level to medication; and under radiation dose range widely; all there is protective effect; wherein combination medicine-feeding is better than individually administration; therefore, breviscapine and glycyrrhizic acid can be used for the treatment of prevention and therapy ionization radiation injury and tumour radiotherapy ancillary drug.
Claims (6)
1. the application in prevention and therapy ionization radiation injury treatment medicine prepared by breviscapine and glycyrrhizic acid.
2. application according to claim 1, wherein said ionization radiation injury treatment includes but not limited to that single fatal dose irradiates the acute ionization radiation injury treatment caused.
3. application according to claim 1, wherein said ionization radiation injury treatment includes but not limited to that the hemopoietic system damage that single/repeatedly low dose exposure causes is given treatment to.
4. application according to claim 1, wherein the use preferred proportion of breviscapine and glycyrrhizic acid is 1: 4 ~ 1: 10.
5. the application in tumour radiotherapy ancillary drug prepared by breviscapine and glycyrrhizic acid.
6. application according to claim 4, wherein said tumour radiotherapy includes but not limited to breast carcinoma.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117121906A (en) * | 2023-10-26 | 2023-11-28 | 深圳市茵冠生物科技有限公司 | Blood preservation solution and preparation method and application thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117121906A (en) * | 2023-10-26 | 2023-11-28 | 深圳市茵冠生物科技有限公司 | Blood preservation solution and preparation method and application thereof |
| CN117121906B (en) * | 2023-10-26 | 2024-02-23 | 深圳市茵冠生物科技有限公司 | Blood preservation solution and preparation method and application thereof |
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Application publication date: 20150408 |