CN106692129A - Simvastatin for reducing toxic and side effects of radiation therapy for abdominal and pelvic tumor - Google Patents
Simvastatin for reducing toxic and side effects of radiation therapy for abdominal and pelvic tumor Download PDFInfo
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- CN106692129A CN106692129A CN201611028614.6A CN201611028614A CN106692129A CN 106692129 A CN106692129 A CN 106692129A CN 201611028614 A CN201611028614 A CN 201611028614A CN 106692129 A CN106692129 A CN 106692129A
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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Abstract
The invention relates to simvastatin for reducing toxic and side effects of radiation therapy for abdominal and pelvic tumor. Specifically, the invention relates to a use of simvastatin or a pharmaceutical composition comprising the same for reducing the toxic and side effects of radiation therapy for abdominal and pelvic tumor.
Description
Technical field
The present invention relates to a kind of new indication of medicine, particularly for reduction basin abdominal tumor radiotherapy toxic and side effect
Simvastatin.
Background technology
The basin such as colorectal cancer, prostate cancer, liver cancer abdominal tumor incidence of disease in the world is pointed out in epidemiological study
Prostatitis is all in fatal rate.Radiotherapy effective oncotherapy means as tradition, in the art of above-mentioned basin abdominal tumor
Before, be widely used in art and in postoperative.But at the same time, due to the characteristic of its own, it is in " kill " tumor group for radiotherapy
While knitting, normal histocyte is inevitably damaged, bring toxic and side effect.Clinical studies show, hemopoietic system pair
Ionising radiation is extremely sensitive, and radiotherapy can cause the irreversible damage of hemopoietic system.Also based on this, many researchs before are all
It is directed to hemopoietic system is damaged caused by ionising radiation treatment and rehabilitation, it has been found that antioxidant and bone-marrow transplantation etc. can
Significantly to alleviate the treatment means of hemopoietic system damage.But, the small intestine of hemopoietic system is only second to as ionizing radiation sensitive
Tissue, and it is not affected by enough concerns.Research display, after basin abdominal tumor radiotherapy, patient all shows different degrees of
The damage of gut integrity and the obstacle of function of intestinal canal.Clinical manifestation is generally poor appetite, diarrhoea and chronic enteritis etc..
The toxic and side effect of enteron aisle drastically influence the quality of life of patient's prognosis caused by these radiotherapies, and more very entail dangers to is to suffering from
The life of person.And so far, not yet occur specifically designed for the medicine for alleviating basin abdominal tumor patient radiation treatment toxic and side effect.
Simvastatin is a kind of oral blood lipid-lowering medicine, mainly acts on HMG CoA (HMG-COA) reduction
On enzyme, the synthesis of endogenous cholesterol can be suppressed, be one of most widely used cardiovascular drugs of Present Global.Simvastatin is not
Only there is good efficacy and saferry evidence, but also be the essential drugs of China with good health economics benefit
One of.Simvastatin is applied to clinical existing nearly 30 years history, also has the Clinical practice experience of nearly 20 years in China, criticizes at present
Accurate indication is the prevention for treating hyperlipidemia and coronary heart disease.
At present, the main application fields of Simvastatin concentrate on cardiovascular system field, do not have any document report to be used for
Reduce in basin abdominal tumor radiotherapy toxic and side effect.
The content of the invention
It is an object of the invention to provide a kind of medicine for alleviating abdominal tumor radiotherapy toxic and side effect --- it is pungent to cut down
Statin is Simvastatin or the pharmaceutical composition containing Simvastatin in new application medically.
Therefore, the present invention provides Simvastatin and is preparing the medicine for reducing basin abdominal tumor radiotherapy toxic and side effect
In purposes.
Prepared for reducing the radiation of basin abdominal tumor the present invention further provides the pharmaceutical composition containing Simvastatin
The purposes in the medicine of toxic and side effect is treated, wherein described pharmaceutical composition contains as the Simvastatin and pharmacy of active component
Upper acceptable carrier.
The chemical name of Simvastatin of the present invention is [1S- [1 α, 3 α, 7 β, 8 β, (2S*, 4S*) 8 α β]] -1,2,
3,7,8,8a- hexahydro -3,7- dimethyl -8- [2- (tetrahydrochysene -4- hydroxyl -6- oxo -2H- pyrans -2- bases) ethyl] -1- naphthyls -
ST20 ester.Structural formula is as follows：
It is known in the art a kind of blood lipid-lowering medicine, with good cardiovascular and cerebrovascular diseases effect.
Pharmaceutically acceptable carrier of the present invention include the conventional diluent of pharmaceutical field, excipient, filler,
Adhesive, wetting agent, disintegrant, sorbefacient, surfactant, absorption carrier, lubricant etc..Those skilled in the art's energy
Enough to understand, pharmaceutical composition of the invention can be formulated into various preparation shapes well known in the art according to specific method of application
Formula, such as peroral dosage form (pulvis, tablet, capsule, soft capsule, oral administration solution, syrup, wine made of broomcorn millet ball, powder, wafer, granule etc.),
Or topical formulation (creme, emulsifiable paste, ointment, lotion, gel, face cream, plaster, paste, spray, aerosol etc.), or note
Penetrate preparation (solution, powder pin, suspending agent, emulsion).The medicine of above-mentioned various formulations can be according to the conventional method of pharmaceutical field
Prepare.Can be made using any known method in this area, so as to quick, lasting or slow release can be provided after patient's medication
Active component.
Active component Simvastatin of the invention can be used alone, it is also possible to which combining with other pharmacy activity components makes
With.Described other pharmacy activity components include the clinical conventional active component with enteron aisle protective effect, such as prostaglandin, big
Flavine, Amifostine, montmorillonite etc..
The dosage of inventive compound can be according to individual situation and weight, the order of severity of the state of an illness, medicine
Form, method of administration and dosage period it is different and different, it can also be selected by those skilled in the art.For example,
The daily dosage of Simvastatin can take or part vic for 1-80mg pauses, can be with successive administration or doses at intervals, each course for the treatment of
Without specific time restriction, can be decided in its sole discretion according to clinical requirement or association area expert judgments.
Pharmaceutical composition of the invention can be applied to by all means individual animals such as mammal (rat, mouse,
Domestication animal or the mankind), all of administering mode is expected.For example, administration can be oral, rectally or through quiet
In arteries and veins, intramuscular, subcutaneous, intracutaneous, sheath, Epidural cavity or intraventricular injection.Can by injection, injection, collunarium, infiltration, absorption,
The method for physically or chemically mediating imports body such as muscle, intracutaneous, subcutaneous, vein, mucosal tissue；Or mixed by other materials
Or import body after parcel.
In a preferred embodiment, according to purposes of the present invention, wherein the pharmaceutically acceptable load
Body is selected from diluent, excipient, filler, adhesive, wetting agent, disintegrant, sorbefacient, surfactant, absorption load
One or more in body and lubricant.
In another preferred embodiment, according to purposes of the present invention, wherein described pharmaceutical composition can be with
It is pulvis, tablet, capsule, soft capsule, oral administration solution, syrup, wine made of broomcorn millet ball, powder, wafer, granule.
In another preferred embodiment, according to purposes of the present invention, wherein described pharmaceutical composition can be with
Containing using the biomaterial work that for example polycaprolactone, polylactic acid-polyglycol, polyvinyl alcohol, albumin nano plasmid are contained
Property composition Simvastatin.
In another preferred embodiment, according to purposes of the present invention, wherein described pharmaceutical composition can be with
Further comprising another or various active components with enteron aisle protective effect, such as prostaglandin, rheum emodin, Amifostine, illiteracy
De- stone.
In another preferred embodiment, according to purposes of the present invention, wherein the basin abdominal tumor is selected from
Stomach cancer, liver cancer, oophoroma and colorectal cancer.
In another preferred embodiment, according to purposes of the present invention, wherein described radiotherapy includes
Three dimensional conformal radiation therapy, gamma knife, and/or ejected wave knife.
In another preferred embodiment, according to purposes of the present invention, wherein described toxic and side effect includes
Intestinal mucosa injury, retardance diarrhoea, acute intestinal are damaged, nauseous, and/or vomiting.
In another preferred embodiment, according to purposes of the present invention, the wherein daily dosage of Simvastatin
It is 1-80mg clothes or part vic.
Composition with enteron aisle protective effect of the present invention refers to by playing physically or chemically effect protection enteron aisle
Epithelial cell, such as material for diminishing inflammation or preventing intestinal wall fibrosis, prostaglandin, rheum emodin, Amifostine, montmorillonite etc..
Basin abdominal tumor of the present invention refers to the basin abdominal swelling occurred in digestive system, urinary system, reproductive system etc.
Knurl, such as stomach cancer, liver cancer, oophoroma, colorectal cancer etc..
Radiotherapy of the present invention refers to α, β, gamma-rays and the treatment of all kinds of x-rays produced using radio isotope
A kind of local therapeutic approaches of tumour, including three dimensional conformal radiation therapy, gamma knife, ejected wave knife etc..
Basin abdominal tumor radiotherapy toxic and side effect of the present invention refers to that radioactive ray is to enteron aisle in addition to normal curative effect
Caused adverse reaction, such as intestinal mucosa injury, retardance diarrhoea, acute intestinal damage, Nausea and vomiting etc..
Brief description of the drawings
Fig. 1 is experiment mice survival rate analysis figure；30 days survival rates of each group experiment mice, Kaplan-Meier survival rates point
Analysis P<0.05.
Fig. 2 is experiment mice changes of weight figure；The changes of weight of each group experiment mice, *, P<0.05；*, P<0.005.
Fig. 3 is experiment mice gut integrity molecular marked compound MDR1 expression variation diagrams；*, P<0.005.
Fig. 4 is experiment mice gut integrity molecular marked compound TTF3 expression variation diagrams；*, P<0.005.
Specific embodiment
The present invention is further detailed below by embodiment, embodiment is served only for that the present invention will be described,
It is not intended that limiting the scope of the present invention, the researcher in the field can make according to foregoing invention content to the present invention
The adjustment and improvement of some non-intrinsically safes.
Influence of the Simvastatin of embodiment 1 to the survival rate and body weight of experiment mice after belly local irradiation
1. model is set up
C57BL/6J mouse (animal is provided consonance) are divided into control group and Simvastatin group, every group 10,1ml/g
After 0.3% chloral hydrate anesthesia experiment mice, use40Exactor (MDS Nordian) is carried out to mouse
12Gy gamma ray belly local irradiations.
2. administering mode
Simvastatin Tablets (Shandeshi (China) pharmaceutical Co. Ltd) are soluble in water, it is stand-by.To Simvastatin group mouse
Simvastatin is given, 2 gastric infusions every afternoon, successive administration 10 days are played after irradiation every other day.Dosage：0.4mg/ml medicines
Thing, every each gavage 200ul.
3. observation index
The death toll and Mouse Weight of every group of mouse are recorded in time.Continuous Observation 30 days, tries to achieve the 30 of each group experiment mice
Its survival rate and average weight.Statistical procedures are carried out with Kaplan-Meier survival Analysis method.
4. check experiment
Control group mice (C57BL/6J mouse 10) receives same illumination, plays 2 gavages every afternoon after irradiation every other day
Give physiological saline, successive administration 10 days.
5. experimental result
30 days survival results of mouse are as shown in figure 1, changes of weight result is as shown in Figure 2.
Test result indicate that：2 gavages every afternoon are played after irradiation every other day and gives Simvastatin, successive administration 10 days, often
1) 80ug, can be improving the survival rate of experiment belly local irradiation mouse；2) reality caused by belly local irradiation is significantly slowed
Test the decline of Mouse Weight.
Thus illustrate, Simvastatin can significantly improve the survival rate and body weight of experiment mice after belly local irradiation, right
Toxic and side effect has significant alleviation caused by radiotherapy.
Effect of the Simvastatin of embodiment 2 to the intestinal tissue integrality of experiment mice after belly local irradiation
1. model is set up
C57BL/6J mouse (animal is provided consonance) are divided into control group and Simvastatin group, every group 10,1ml/g
After 0.3% chloral hydrate anesthesia experiment mice, use40Exactor (MDS Nordian) is carried out to mouse
12Gy gamma ray belly local irradiations.
2. administering mode
Simvastatin (Shandeshi (China) pharmaceutical Co. Ltd) is soluble in water, it is stand-by.Simvastatin group mouse is given
Simvastatin is given, 2 gastric infusions every afternoon, successive administration 10 days are played after irradiation every other day.Dosage：0.4mg/ml medicines
Thing, every each gavage 200ul.
3. observation index
Mouse is put to death after 15 days, mouse small intestine tissue is taken, RNA is extracted, with Real-time quantitative PCR (SYBRGreenl
Method) expression of the detection mouse intestinal integrality label MDR1 and TTF3 in each group.
4. check experiment
Control group mice (C57BL/6J mouse 10) receives same illumination, plays 2 gavages every afternoon after irradiation every other day
To physiological saline, successive administration 10 days.
5. experimental result
Experiment mice gut integrity molecular marked compound expression change is as shown in Figure 3 and Figure 4.
Test result indicate that：2 gavages every afternoon are played after irradiation every other day and gives Simvastatin, successive administration 10 days, often
80ug, can significantly improve the expression of mouse intestinal integrality molecular marked compound.
Thus illustrate, Simvastatin can improve the integrality of experiment mice intestinal tissue after belly local irradiation, reduce abdomen
Toxic and side effect caused by portion's local irradiation.
Claims (10)
1. Simvastatin prepare for reduce basin abdominal tumor radiotherapy toxic and side effect medicine in purposes.
2. the pharmaceutical composition containing Simvastatin is preparing the medicine for reducing basin abdominal tumor radiotherapy toxic and side effect
In purposes, wherein described pharmaceutical composition contains as the Simvastatin and pharmaceutically acceptable carrier of active component.
3. purposes according to claim 2, wherein the pharmaceutically acceptable carrier is selected from diluent, excipient, fills out
The one kind or many filled in agent, adhesive, wetting agent, disintegrant, sorbefacient, surfactant, absorption carrier and lubricant
Kind.
4. the purposes according to Claims 2 or 3, wherein described pharmaceutical composition can be pulvis, tablet, capsule, flexible glue
Capsule, oral administration solution, syrup, wine made of broomcorn millet ball, powder, wafer, granule.
5. the purposes according to any one of claim 2 to 4, wherein described pharmaceutical composition can be containing using biological materials
The active component Simvastatin that material is contained such as polycaprolactone, polylactic acid-polyglycol, polyvinyl alcohol, albumin nano plasmid.
6. the purposes according to any one of claim 2 to 5, wherein described pharmaceutical composition can further comprising another
Plant or various active components with enteron aisle protective effect such as prostaglandin, rheum emodin, Amifostine, montmorillonite.
7. purposes according to any one of claim 1 to 6, wherein the basin abdominal tumor is selected from stomach cancer, liver cancer, ovary
Cancer and colorectal cancer.
8. purposes according to any one of claim 1 to 7, wherein described radiotherapy include three dimensional conformal radiation therapy,
Gamma knife, and/or ejected wave knife.
9. purposes according to any one of claim 1 to 8, wherein described toxic and side effect includes intestinal mucosa injury, prolongs
Slow property diarrhoea, acute intestinal are damaged, nauseous, and/or vomiting.
10. purposes according to any one of claim 1 to 9, the wherein daily dosage of Simvastatin are 1-80mg clothes
Or part vic.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611028614.6A CN106692129A (en) | 2016-11-18 | 2016-11-18 | Simvastatin for reducing toxic and side effects of radiation therapy for abdominal and pelvic tumor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611028614.6A CN106692129A (en) | 2016-11-18 | 2016-11-18 | Simvastatin for reducing toxic and side effects of radiation therapy for abdominal and pelvic tumor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106692129A true CN106692129A (en) | 2017-05-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201611028614.6A Pending CN106692129A (en) | 2016-11-18 | 2016-11-18 | Simvastatin for reducing toxic and side effects of radiation therapy for abdominal and pelvic tumor |
Country Status (1)
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004024073A2 (en) * | 2002-09-11 | 2004-03-25 | The Board Of Trustees Of The University Of Arkansas | Use of statins in the prevention and treatment of radiation injury and other disorders associated with reduced endothelial thrombomodulin |
-
2016
- 2016-11-18 CN CN201611028614.6A patent/CN106692129A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004024073A2 (en) * | 2002-09-11 | 2004-03-25 | The Board Of Trustees Of The University Of Arkansas | Use of statins in the prevention and treatment of radiation injury and other disorders associated with reduced endothelial thrombomodulin |
Non-Patent Citations (3)
| Title |
|---|
| BIJI MATHEW等: "Simvastatin Attenuates Radiation-Induced Murine Lung Injury and Dysregulated Lung Gene Expression", 《AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY》 * |
| JUNRU WANG等: "SIMVASTATIN AMELIORATES RADIATION ENTEROPATHY DEVELOPMENT AFTER LOCALIZED, FRACTIONATED IRRADIATION BY A PROTEIN C-INDEPENDENT MECHANISM", 《INT. J. RADIATION ONCOLOGY BIOL. PHYS.》 * |
| 赵心彬: "辛伐他汀改善辐射诱导的小鼠组织损伤", 《第二军医大学硕士学位论文》 * |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170524 |
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| WD01 | Invention patent application deemed withdrawn after publication |