CN102406921B - Medical application of GHGKHKNK octopeptide with anti-tumor synergetic effect on 5-fluorouracil - Google Patents
Medical application of GHGKHKNK octopeptide with anti-tumor synergetic effect on 5-fluorouracil Download PDFInfo
- Publication number
- CN102406921B CN102406921B CN2011103635296A CN201110363529A CN102406921B CN 102406921 B CN102406921 B CN 102406921B CN 2011103635296 A CN2011103635296 A CN 2011103635296A CN 201110363529 A CN201110363529 A CN 201110363529A CN 102406921 B CN102406921 B CN 102406921B
- Authority
- CN
- China
- Prior art keywords
- ghgkhknk
- octapeptide
- octopeptide
- group
- fluorouracil
- 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.)
- Expired - Fee Related
Links
Images
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses application of GHGKHKNK octopeptide in preparation of medicaments with an anti-tumor synergetic effect on 5-fluorouracil and provides an synergetic effect of GHGKHKNK octopeptide on anti-cancer medicaments. The GHGKHKNK octopeptide can achieve a better effect when being used together with 5-Fu; and the GHGKHKNK octopeptide can be used for enhancing the anti-cancer effect of 5-Fu and simultaneously obviously reducing the toxic and side effects of 5-Fu, thereby providing a better method for treating cancers.
Description
Technical field
The present invention relates to the potentiation of GHGKHKNK octapeptide to cancer therapy drug, especially disclose the GHGKHKNK octapeptide preparing the purposes in the medicine of 5-fluorouracil antitumor potentiation, belong to medical science pharmaceutical technology field.
Background technology
At present, cancer has become one of principal disease that causes mankind's death.According to World Health Organization's report, annual have 10 million to play new cases of cancer generation in the world.The main method for the treatment of cancer comprises at present: the chemotherapy of operative treatment, cancer therapy drug, radiotherapy and biological response modifier and other treatment.But, the poor selectivity of cancer therapy drug, toxic and side effects is large, so the use in treatment of cancer is restricted.For example: 5-fluorouracil (5-fluorouracil, be called for short: be 5-Fu) one of most widely used in the world anticarcinogen, be also one of the most frequently used intra-abdominal chemotherapy medicine, be used for the treatment of clinically the kinds cancers such as colorectal cancer, gastric cancer, hepatocarcinoma, breast carcinoma.The 5-Fu antitumor spectra is wide, but internal metabolism is fast, and the half-life is short, and the serious toxicity reaction is arranged, and can cause Bone Marrow of Patients inhibition and hemorrhagic enteritis etc.Therefore, 5-Fu general with other antitumor drug compatibilities uses.Therefore, design a kind of material and cancer therapy drug and unite treatment for cancer, and by giving full play to advantage separately, with the active anticancer that improves medicine, the toxicity that reduces cancer therapy drug, this is a kind of method of received treatment cancer.
With GHGKHKNK octapeptide and cancer therapy drug 5-FU use in conjunction,, to strengthen the antitumaous effect of 5-FU, reduce its toxic and side effects,, better to be applied to the treatment of cancer, be the task that the present invention will realize.
Summary of the invention
The invention provides the GHGKHKNK octapeptide and preparing the purposes in the medicine of 5-fluorouracil antitumor potentiation, purpose is to reduce drug toxicity by drug combination, improves the cancer therapy drug property of medicine.
The GHGKHKNK octapeptide that the present invention relates to (hereinafter to be referred as: octapeptide) have following primary structure:
Gly-His-Gly-Lys-His-Lys-Asn-Lys, that containing of selecting from the 5th domain of people's high-molecular-weight kininogen can be at the octapeptide compounds of vitro inhibition cell adhesion and the crucial block His-Gly-Lys of infiltration, it is a kind of natural micromolecule polypeptide, glycine, histidine, glycine, lysine, histidine, lysine, agedoite, eight aminoacid of lysine, consists of.
Great many of experiments by GHGKHKNK octapeptide and the potentiation of 5-Fu coupling medication enhanced sensitivity, the proof octapeptide shows the inhibitory action of height to hepatoma carcinoma cell and animal Hepatic neoplasm model, suppress the transfer of hepatoma carcinoma cell, suppress the generation of rat liver cancer ascites, extend the life cycle of tumor model Mus, can strengthen the anticancer property of medicine of multi-medicament, it can be prepared into new antitumor drug and antitumor sensitizer, particularly GHGKHKNK octapeptide can also significantly reduce its toxic and side effects when strengthening the 5-Fu antitumaous effect.
The GHGKHKNK octapeptide can be medicinal preparation for oral administration or injection medicament as the dosage form of sensitizing and potentiating agent of medicament for resisting liver cancer, described medicinal preparation for oral administration can be drop pill, soft capsule or freeze-dried powder etc., described injection medicament can be injectable emulsion etc., injectable emulsion can be used for intravenous injection Emulsion, intramuscular injection with Emulsion, lumbar injection with Emulsion or subcutaneous injection with Emulsion etc.
Good effect of the present invention is:
The synergistic function of GHGKHKNK octapeptide to cancer therapy drug is provided, and better effects if during with the 5-Fu coupling, can also significantly reduce its toxic and side effects when strengthening the 5-Fu antitumaous effect, for the treatment of cancer provides better method.
Description of drawings
Fig. 1 is that the invention experimental example is respectively organized the Mouse Weight change curve;
Fig. 2 is invention experimental example flow cytometer testing result;
Fig. 3 is that the invention experimental example is respectively organized the survival time of mice curve;
Wherein, 1, blank group; 2, octapeptide low dose group; 3, dosage group in octapeptide; 4, octapeptide high dose group; 5,5-FU high dose group; 6,5-FU low dose group; 7, administering drug combinations group.
The specific embodiment
According to method known in medical industry,, with the medicine of GHGKHKNK octapeptide as the synergy effect of 5-Fu, with one or more pharmaceutically acceptable carriers or excipient, mix mutually, can make the pharmaceutical composition of various different dosage forms.Comprise medicinal preparation for oral administration or injection medicament, described medicinal preparation for oral administration can be drop pill, soft capsule or freeze-dried powder etc., described injection medicament can be injectable emulsion etc., injectable emulsion can be used for intravenous injection Emulsion, intramuscular injection with Emulsion, lumbar injection with Emulsion or subcutaneous injection with Emulsion etc.
Following experimental example tests to further illustrate the present invention by GHGKHKNK octapeptide and the anticancer pharmacological effect of 5-Fu coupling, but does not represent that the present invention is only limited to this embodiment.
Below experiment shows that further the present invention improves cancer therapy drug property of medicine therapeutic effect:
This experiment adopts GHGKHKNK octapeptide and 5-Fu coupling to treat hepatic ascites tumor Mus, and observation GHGKHKNK octapeptide reaches both therapeutic effect of coupling to the potentiation of 5-Fu.
The pharmacodynamic experiment of octapeptide, 5-FU composition of medicine:
1, the foundation of animal model
With the H22 cell culture in 37 ℃, 5%CO
2Contain in the RPMI-1640 culture fluid of 10% hyclone, the cell of collecting exponential phase dilutes with RPMI-1640, makes single cell suspension, and with 0.4% Trypan Blue living cell counting number＞95%, being diluted to cell number with NaCl subsequently is 10
7/ uL.Get 200 these cell suspension inoculations of μ l in 2 KM mices (male, 20-22g) abdominal cavity, aseptic extraction mouse ascites after the week, adjust cell concentration to 2.5 * 10 with normal saline
6/ mL, every mouse peritoneal injection 0.2mL(5 * 10
5Cell/ is only) structure mouse ascites tumor model.
2, experiment grouping and administration
Get 12 normal mouses and do blank group, model mouse is divided into 7 groups at random, be respectively dosage group (50 μ g/kg.d), octapeptide high dose group (200 μ g/kg.d), 5-Fu high dose group (20 mg/kg.d), 5-Fu low dose group (5 mg/kg.d), octapeptide and 5-Fu drug combination group in blank group (normal saline), octapeptide low dose group (12.5 μ g/kg.d), octapeptide (5 mg/kg.d 5-Fu ﹢ 12.5 μ g/kg.d octapeptides), 18 every group.Give respectively drug treating after grouping, the medicine of every group of per injection is 0.2 ml, continuous use 30d.Only the 5-Fu high dose group was administered once every 1 day, all the other medication group successive administration 30d.Put to death and respectively to organize mice and carry out index of correlation and detect with the dislocation of cervical vertebra method in the 2nd day after drug withdrawal.Aspect research life cycle, each is organized mice and starts to observe after tumor cell inoculation until dead.
3, detect index and detection method
3.1 observe the general state of respectively organizing mice
In experimentation, the next day observe the variation respectively organize mice diet, the mental status and build etc.
Respectively organize the Mice Body mass change 3.2 observe
From inoculation, next day monitoring 8 groups of mices (12 of every group selections) body weight and record, result is carried out statistical procedures, draws form.
3.3 oncocyte and mean constant of red blood cell in mouse ascites average external volume and mouse ascites respectively organized in record
Get 6 mices for every group, open abdomen under aseptic condition after the dislocation of cervical vertebra method is put to death, collect ascites with aseptic straw and enter centrifuge tube, calculate the ascites volume.And leave and take the detection of ascites specimen line correlation index.Each specimen is got ascites 50 μ l in above-mentioned specimen, dilutes 10 times, by the numeration of leukocyte method, records leukocyte and mean constant of red blood cell.
3.4 flow cytometer detects the cell cycle in mouse ascites
Put to death mice, collect mouse ascites, add the ammonium chloride erythrocyte cracked liquid, after centrifugal 3 min of 1500 r/min,, with centrifugal 3 times of PBS washing, add 70% cold ethanol 0.5 ml to fix.Machine testing cell cycle on after placing 30 min under 4 ℃ of conditions.
3.5 observe and record the life cycle of respectively organizing mice
The time-to-live of mice respectively organized in record, and result is carried out statistical procedures, draws form.
4, experimental result
4.1 respectively organize the general state of mice
After inoculation 5-8d, blank group Mice Body quality increases sharply, and engenders subsequently depressed, dull few moving, the instability of gait of lethargy, and is reactive poor, water inlet feed reduces, and feces is dry, abdominal part in late period bulge extremely, be the dyscrasia state, dead speed is very fast, and is all dead in 30 days.It is slower that octapeptide and 5-Fu unite the group Weight gain, and better, life cycle is very long for spirit.Though other groups are improved, drug combination group curative effect is best.
4.2 respectively organizing Mouse Weight changes
Mouse Weight changes statistics as shown in Figure 1, and the Mouse Weight change curve shows, with the blank group, compares, except octapeptide high dose group and its similar trend, all the other each medication group Mouse Weight increases are all slower, but gathering way of drug combination group is the slowest, and are almost identical with normal group.Although the body weight change of 5-Fu group is also very slow, toxicity is large, and Mouse Weight decline is fast and mortality rate is high.
4.3 respectively organize oncocyte and mean constant of red blood cell in mouse ascites average external volume and mouse ascites
In mouse ascites average external volume and mouse ascites, oncocyte and mean constant of red blood cell statistical result are in Table 1, compare with the blank group, the ascites average external volume of each medication group mice diminishes, in ascites, oncocyte and mean constant of red blood cell descend, wherein the ascites average external volume of 5-Fu high dose group and drug combination group mice is minimum, in ascites, oncocyte and mean constant of red blood cell descend at most, but 5-Fu high dose group mouse death rate is high, and drug combination group mice is in good condition and without death.
Table 1 is respectively organized oncocyte and mean constant of red blood cell in mouse ascites average external volume and mouse ascites
| Grouping | n | Ascites volume (ml) | Oncocyte number (10 7/mL） | RBC number (10 7/mL） |
| |
5 | 7.9±1.91 | 8.06±1.48 | 13.52±7.47 |
| The octapeptide low dosage | 6 | 4.13±2.80 | 5.47±2.03 | 2.57±2.85 |
| Dosage in octapeptide | 6 | 1.6±1.55 | 2.43±2.3 | 1.6±1.74 |
| The octapeptide high dose | 4 | 5.4±3.91 | 7.6±3.58 | 8.98±5.89 |
| The 5-Fu high dose | 4 | 0.1±0.14 | 0 | 0 |
| The 5-Fu low dosage | 6 | 4.38±2.65 | 5.38±2.95 | 2.77±2.17 |
| Administering drug combinations of the present invention | 6 | 0.38±0.48 | 0.58±0.94 | 0 |
4.4 flow cytometer detects the cell cycle in mouse ascites
As Fig. 2, the oncocyte number that is in the S phase in administering drug combinations group mouse ascites obviously is less than the blank group.
4.5 respectively organize situation life cycle of mice
Each situation life cycle of organizing mice is added up as Fig. 3, and each organizes survival time of mice all than blank group leader, and wherein octapeptide and 5-Fu drug combination group survival time of mice are the longest.
By above experimental result as can be known, although all having certain effect aspect alleviating the mouse peritoneal tumor load, suppress the ascites generation and extending life cycle when GHGKHKNK octapeptide and the independent medication of 5-Fu, but better effects if during coupling both, this has shown that fully the GHGKHKNK octapeptide can also significantly reduce its toxic and side effects when strengthening the 5-Fu antitumaous effect.
Claims (1)
1.GHGKHKNK the purposes of octapeptide in the medicine of preparation anti-hepatic ascites potentiation to 5-fluorouracil.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103635296A CN102406921B (en) | 2011-11-16 | 2011-11-16 | Medical application of GHGKHKNK octopeptide with anti-tumor synergetic effect on 5-fluorouracil |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103635296A CN102406921B (en) | 2011-11-16 | 2011-11-16 | Medical application of GHGKHKNK octopeptide with anti-tumor synergetic effect on 5-fluorouracil |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102406921A CN102406921A (en) | 2012-04-11 |
| CN102406921B true CN102406921B (en) | 2013-11-13 |
Family
ID=45909456
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011103635296A Expired - Fee Related CN102406921B (en) | 2011-11-16 | 2011-11-16 | Medical application of GHGKHKNK octopeptide with anti-tumor synergetic effect on 5-fluorouracil |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102406921B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101270145A (en) * | 2008-05-07 | 2008-09-24 | 北华大学 | Preparation technique for GHGKHKNK octapeptide and medicine use |
-
2011
- 2011-11-16 CN CN2011103635296A patent/CN102406921B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101270145A (en) * | 2008-05-07 | 2008-09-24 | 北华大学 | Preparation technique for GHGKHKNK octapeptide and medicine use |
Non-Patent Citations (4)
| Title |
|---|
| GHGKHKNK八肽对小鼠黑色素瘤细胞B16-F10侵袭和转移的抑制作用;吕刚 等;《吉林大学学报(医学版)》;20080930;第34卷(第5期);第825-828页 * |
| GHGKHKNK八肽对肿瘤细胞克隆形成、黏附及体外侵袭能力的影响;吕刚 等;《中国老年学杂志》;20080831;第28卷;第1470-1472页 * |
| 吕刚 等.GHGKHKNK八肽对小鼠黑色素瘤细胞B16-F10侵袭和转移的抑制作用.《吉林大学学报(医学版)》.2008,第34卷(第5期),第825-828页. |
| 吕刚 等.GHGKHKNK八肽对肿瘤细胞克隆形成、黏附及体外侵袭能力的影响.《中国老年学杂志》.2008,第28卷第1470-1472页. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102406921A (en) | 2012-04-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kodama et al. | Can maitake MD-fraction aid cancer patients? | |
| CN102440986B (en) | Application of arctigenin in preparation of medicines for preventing and treating bone marrow suppression caused by radiation or chemicals | |
| CN101601695B (en) | Self-microemulsion nanometer composition of ganodenic acid extract and preparation method thereof | |
| CN104434939B (en) | Antitumor medicament composition of panax notoginseng saponins R7 and oridonin with capabilities of reducing toxicity and enhancing efficacy and application of antitumor medicament composition | |
| CN105476996A (en) | Application of curcumin and afatinib for combined treatment of non-small cell lung cancer | |
| CN101143148B (en) | Application of paris saponin I and its derivatives | |
| CN109662968B (en) | A-nor-5 alpha androstane compound-containing leucocyte increasing preparation and application thereof | |
| CN102406921B (en) | Medical application of GHGKHKNK octopeptide with anti-tumor synergetic effect on 5-fluorouracil | |
| CN101167741B (en) | Sulforaphane and platinum medicine anti-cancer combination preparation | |
| CN104622864A (en) | Application of chlorogenic acid in preparing drugs for prevention and treatment of primary cutaneous T-cell lymphoma | |
| CN115300624A (en) | Application of ginsenoside and PD-1 blocker in preparation of head and neck squamous cell carcinoma resisting medicine | |
| CN104189782A (en) | Anti-tumor medicament composition | |
| CN101507747B (en) | Preparation method of astragalus total-saponin sodium chloride injector | |
| US8003137B2 (en) | Extracts of Aristolochia paucinervis pomel and uses thereof | |
| CN102727867B (en) | Antineoplastic pharmaceutical composition and application thereof, kit and package | |
| CN102614283A (en) | Medicament for promoting postoperative gastrointestinal function recovery and application of medicament | |
| De Vries et al. | Drug resistance, supportive care and dose intensity | |
| CN103405542B (en) | Traditional Chinese medicine for treating leucopenia after chemotherapy | |
| CN104146999A (en) | Oridonin and docetaxel toxicity reducing and efficacy enhancing antitumor drug composition and application thereof | |
| CN104138386A (en) | Medical application of saikosaponin D to tumor multi-drug resistance reversion effect | |
| CN102139037A (en) | Application of rhizoma paridis total saponins in preparation of adjuvant drugs of anti-cancer drugs | |
| CN102309493B (en) | Anti-cancer medicinal composition | |
| CN102440994A (en) | Application of ganoderic acid G as immune synergist and super-antigen dependent therapeutic medicine in tumour treatments | |
| CN102872374B (en) | Chinese medicinal composition for assisting tumor radiotherapy | |
| CN101797242A (en) | Application of cysteamine in preparing medicine for treating cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Du Peige Inventor after: Wang Tuo Inventor after: Li Tancheng Inventor after: Han Xiao Inventor after: An Liping Inventor after: Wang Manli Inventor after: Xu Guangyu Inventor after: Jiang Shuang Inventor after: Li Na Inventor after: Zhan Jinzhuo Inventor after: Sun Hui Inventor before: Du Peige Inventor before: Li Tancheng Inventor before: Han Xiao Inventor before: An Liping Inventor before: Li Na Inventor before: Xu Guangyu Inventor before: Jiang Shuang Inventor before: Zhan Jinzhuo Inventor before: Sun Hui Inventor before: Wang Tuo |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: DU PEIGE HAN XIAO AN LIPING LI NA XU GUANGYU JIANG SHUANG ZHAN JINZHUO SUNHUI WANG TUO LI TANCHENG TO: DU PEIGE HAN XIAO AN LIPING WANG MANLI XU GUANGYU JIANG SHUANG LI NA ZHAN JINZHUO SUN HUI WANG TUO LI TANCHENG |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20131113 Termination date: 20141116 |
|
| EXPY | Termination of patent right or utility model |