CN103893166A - Pharmaceutical composition for resisting chemotherapy induced bone marrow suppression and application thereof - Google Patents
Pharmaceutical composition for resisting chemotherapy induced bone marrow suppression and application thereof Download PDFInfo
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- CN103893166A CN103893166A CN201410137511.8A CN201410137511A CN103893166A CN 103893166 A CN103893166 A CN 103893166A CN 201410137511 A CN201410137511 A CN 201410137511A CN 103893166 A CN103893166 A CN 103893166A
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Abstract
The invention discloses a pharmaceutical composition for resisting chemotherapy induced bone marrow suppression and application thereof. The pharmaceutical composition is prepared from an active ingredient and accessories, wherein the active ingredient comprises quercetin and/or a derivative thereof. The quercetin not only has an antitumor activity but also is capable of significantly improving the quantity of leukocytes after chemotherapy, and especially the quercetin has the bioactivity of increasing the quantity of neutrophils, showing that the quercetin and the derivative thereof are expected to be developed as a medicine for resisting chemotherapy induced bone marrow suppression.
Description
Technical field
The invention belongs to chemotherapy bone marrow depression practical technique field, be specifically related to the myelosuppressive pharmaceutical composition of a kind of anti-chemotherapy and application thereof.
Background technology
Leukocyte comprises neutrophilic granulocyte, eosinophilic granulocyte and basophilic granulocyte, and leukocyte is by bone marrow hematogenesis, clinically; tumour patient is being accepted after medicine chemotherapy; usually there will be bone marrow depression, thereby peripheral white blood cell amount is reduced, neutrophilic granulocyte quantity reduces.Human peripheral blood neutrophilic granulocyte accounts for the 50-70% of total white blood cells, and it increases and lower the variation that directly affects total white blood cells, and neutrophilic granulocyte increases, and leukocyte increases thereupon; Neutrophilic granulocyte lowers, and total white blood cells also lowers thereupon.Both also show the concordance in meaning by dependency quantitatively, i.e. the meaning of neutrophilic granulocyte increase and decrease with in the meaning of the increase and decrease of total white blood cells, be consistent substantially.
The hemopoietic system of human body is made up of the hematopoietic cell of a small amount of marrow hemopoietic stem cells and different development stage different series, harmful factor to various physical chemistry and internal metabolism generation is very responsive, such as body is exposed to radiation or some chemotherapeutics, and the patient who accepts clinically radiotherapy, chemotherapy very easily sustains damage and occurs bone marrow depression in various degree, show as that peripheral blood leucocyte reduces, aplastic anemia even occurs bone marrow proliferation function reduction, patient's life quality is caused to even threat to life of serious harm.Once suffer from cancer, patient will use antitumor drug within considerable time, and most antitumor drug equal (the most serious with alkylating agent) can cause bone marrow depression in various degree, main manifestations is leukopenia, and especially neutrophilic granulocyte reduces the most remarkable.Radiotherapy chemotherapy remains means the most frequently used in oncotherapy at present, but the complication such as the bone marrow hematogenesis inhibition causing after treatment become the major reason that affects life in patients.Some oncotherapy assistant chemical medicines with clear and definite curative effect itself will produce more untoward reaction after use, have increased patient's misery.Many medical personnels are being devoted to find some effectively but the few medicine of side reaction resists the infringement that Radiotherapy chemotherapy brings.
Give various somatomedin to occurring that mostly bone marrow depression is to adopt clinically at present, to increase the propagation of hematopoietic cell.The hemopoietic growth factor of the gene recombinaton of just having gone on the market this year is as SHENGBAINENG (rhGM-GSF), G-CSF (rhG-CSF) etc., it is remarkable to be used for leukocyte increasing effect, but because of expensive, be not that most patients can bear, and rhGM-GSF, rhG-CSF cannot use in chemotherapy, also cannot prevent to use, can only in the time there is leukopenia, use, otherwise can produce by toxic side effect.In addition, the gene therapy of hemopoietic growth factor is if the gene therapy such as IL-6, IL-3 is still in the animal experiment stage, is used in conjunction with, but is difficult to repeatedly apply when high-dose chemotherapy is everlasting in self bone marrow depression.Therefore, find a kind of side reaction of safe, effective, inexpensive method antagonism chemotherapy, rising Leukocytes after Chemotherapy, for the chemotherapy effect that improves tumor, extends cancer patient's life cycle, and improving life quality has very important meaning.
(quercetin, is called for short QU to Quercetin, is 3,4,5 ', 3 ', 4 ',-pentahydroxyflavone) and derivant be distribute the widest flavone compound of plant kingdom, there is multiple biological activity and very high medical value, be also topmost bioflavonoids in human diet.In recent years, the performance of Quercetin caused the extensive concern of Chinese scholars, and its biological activity, pharmacological action have all been carried out to a large amount of research.Quercetin has the multiple pharmacological effect such as coronary artery dilator, reduction capillary permeability and fragility, antiviral, antiinflammatory, antitumor, fibrosis, antiplatelet aggregation, antiallergic, analgesia, antioxidation, removing free radical.
Find by retrieving domestic and international prior art, also do not adopt at present Quercetin or derivatives thereof treatment chemotherapeutics to cause myelosuppressive bibliographical information.
Summary of the invention
When adopting cyclophosphamide combined Quercetin for anticancer research, the inventor finds unexpectedly, Quercetin not only has anti-tumor activity, and can significantly improve the quantity of Leukocytes after Chemotherapy, especially have the biological activity that improves neutrophilic granulocyte quantity, this is indicating that Quercetin and its derivant are expected to be developed to the myelosuppressive medicine of anti-chemotherapy.
On this basis, the inventor has carried out more deep research, finds that Quercetin commissural arch phosphamide is showing beyond thought synergism aspect treatment tumor-bearing model, and it can not only strengthen tumour inhibiting rate, and can accelerate bone marrow hematogenesis.Therefore the object of the present invention is to provide the myelosuppressive pharmaceutical composition of a kind of anti-chemotherapy and application thereof.
The object of the present invention is achieved like this:
The myelosuppressive pharmaceutical composition of a kind of anti-chemotherapy, is prepared from by active component and adjuvant, and described active component comprises Quercetin or/and its derivant.
Preferably, the myelosuppressive pharmaceutical composition of anti-chemotherapy described above, wherein said active component is made up of Quercetin.
Further preferably, the myelosuppressive pharmaceutical composition of anti-chemotherapy described above, it can be made into ejection preparation, comprises injection, injection lyophilized powder.
The present invention proves by zoopery, Quercetin and cyclophosphamide are combined with can synergistic antitumor simultaneously, it has alleviated the bone marrow depression that cyclophosphamide brings when performance suppresses tumor growth, in ensureing tumour inhibiting rate, can promote bone marrow hematogenesis, thereby increase quantity of leucocyte, increase neutrophilic granulocyte quantity, reduced to a certain extent side reaction.Therefore, the present invention also provides a kind of pharmaceutical applications, that is: Quercetin is or/and the application of its derivant in the myelosuppressive medicine of the anti-chemotherapy of preparation.Preferred scheme is: Quercetin is the application in the myelosuppressive medicine of the anti-chemotherapy of preparation as unique active component.Further preferred scheme is: the application in the myelosuppressive medicine that Quercetin causes at the anti-cyclophosphamide of preparation as unique active component.
It should be noted that, the inventor finds that bone marrow depression that Quercetin causes cyclophosphamide has the antagonism of highly significant, but, regrettably, Quercetin can not be treated the bone marrow depression that all cancer therapy drugs cause, such as evidence its can not antagonism vinca, the bone marrow depression that causes for anticarcinogens such as Buddhist nun's class medicines.
Compared with prior art, the pharmaceutical composition tool the present invention relates to has the following advantages and marked improvement:
(1) for chemotherapy bone marrow depression provides new drug candidate, can use with this based chemotherapy medicine of cyclophosphamide simultaneously, also can, separately as the myelosuppressive drug use of prevention, there is very important clinical meaning.
(2) in treatment cancer, prevent leucocytes reduction, even improve the granulocytic quantity in center, thereby improve the chemotherapy effect of tumor, extend cancer patient's life cycle, improve life quality.
Detailed description of the invention
Be below specific embodiments of the invention, technical scheme of the present invention is done to further description, but protection scope of the present invention is not limited to this embodiment.Every do not deviate from the change of the present invention design or be equal to substitute include within protection scope of the present invention.
Embodiment Quercetin is to the myelosuppressive antagonism research of chemotherapy
By mouse ascites tumor S180 cell culture in RPMI-1640,37 DEG C, 5%CO
2lower cellar culture, on average goes down to posterity once for every two days, and during to exponential phase, being prepared into density with normal saline is 3.0 × 10
7individual/ml single cell suspension, at aseptic condition hemostasis in KM mouse peritoneal, inoculate latter 7 days and see the obvious enlargement of mouse peritoneal, now, de-neck is put to death, and puts into the beaker that fills 75% ethanol and soaks 2～3 minutes, and the mice after sterilization is put into superclean bench, expose abdominal part, put into aseptic reagent bottle by asepsis injector extraction ascites for subsequent use.Above-mentioned ascites is counted with trypan blue, with normal saline dilution, adjusted cell number to 2.0 × 10
7individual/ml, is inoculated in the right oxter of KM mice of body weight 18～22g, every 0.2ml.
By postvaccinal 7 week age KM mice be divided at random blank group, cyclophosphamide (CTX) group, Quercetin+cyclophosphamide (QU+CTX) group, 12 every group, male and female half and half, the normal solid feed of feeding, freely drinks water.Each treated animal specifically gives corresponding tested material by the medicine of table 1 and dosage:
The grouping of table 1 laboratory animal and administration
| Group | Sample size (only) | Dosage |
| Blank group | 12 | The normal saline of injection same volume |
| CTX group | 12 | Injection 50mg/kg/d cyclophosphamide |
| QU+CTX group | 12 | Injection 10mg/kg/d Quercetin+50mg/kg/d cyclophosphamide |
Cyclophosphamide and Quercetin intraperitoneal injection, administration volume is 20ml/kg.Each group is administered once every day, altogether two weeks.In process of the test, observe animal diet followed, survival condition and behavioral activity every day, after off-test, anesthesia is dissected, and abdomen cardinal vein is got blood, surveys routine blood test, investigates total white blood cells and neutrophilic granulocyte sum.Result of the test is in table 2.
Result of the test by table 2 can find out, compared with blank group, the total white blood cells of cyclophosphamide group and neutrophilic granulocyte number all significantly reduce (
p< 0.01); Compared with CTX group, all significantly increases of the total white blood cells of QU+CTX group and neutrophilic granulocyte number (
p< 0.01); This is indicating that Quercetin and cyclophosphamide combine with can synergistic antitumor simultaneously, it has alleviated the bone marrow depression that cyclophosphamide brings when performance suppresses tumor growth, in ensureing tumour inhibiting rate, can promote bone marrow hematogenesis, thereby increase quantity of leucocyte, increase neutrophilic granulocyte quantity, reduced to a certain extent side reaction.
The impact of table 2 Quercetin on chemotherapy murine interleukin and neutrophilic granulocyte quantity
| Group | Sample size (only) | Leukocyte (10 9Individual/L) | Neutrophilic granulocyte (10 9Individual/L) |
| Blank group | 12 | 3.31±0.40 | 1.08±0.19 |
| CTX group | 12 | 1.36±0.52 ** | 0.27±0.13 ** |
| QU+CTX group | 12 | 3.07±0.68 ￥￥ | ?1.10±0.22 ￥￥ |
With the comparison of blank group,
* p< 0.05,
* p< 0.01; Compare with CTX group,
$ p< 0.05,
$$ p< 0.01.
Claims (6)
1. the myelosuppressive pharmaceutical composition of anti-chemotherapy, is prepared from by active component and adjuvant, it is characterized in that: described active component comprises Quercetin or/and its derivant.
2. the myelosuppressive pharmaceutical composition of anti-chemotherapy according to claim 1, is characterized in that: described active component is made up of Quercetin.
3. the myelosuppressive pharmaceutical composition of anti-chemotherapy according to claim 1, is characterized in that: described pharmaceutical composition is injection, described injection comprises injection, injection lyophilized powder.
4. Quercetin is or/and the application of its derivant in the myelosuppressive medicine of the anti-chemotherapy of preparation.
5. Quercetin application in the myelosuppressive medicine of the anti-chemotherapy of preparation as unique active component.
6. application according to claim 5, is characterized in that: described chemotherapy bone marrow depression is the bone marrow depression that cyclophosphamide causes.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110501483A (en) * | 2019-07-25 | 2019-11-26 | 同济大学 | A kind of active detection method of Chinese herbal medicine |
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2014
- 2014-04-08 CN CN201410137511.8A patent/CN103893166A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| SALEHA. BAKHEET: "Assessment of Anti-Cytogenotoxic Effects of Quercetin in Animals Treated with Topotecan", 《OXIDATIVE MEDICINE AND CELLULAR LONGEVITY》 * |
| SRINIVAS H R等: "EFFECT OF QUERCETIN ON MICRONUCLEUS STUDY IN MICE", 《INTERNATIONAL JOURNAL OF LIFE SCIENCES BIOTECHNOLOGY AND PHARMA RESEARCH》 * |
| 马增春等: "环磷酰胺损伤小鼠骨髓造血的机制", 《毒理学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110501483A (en) * | 2019-07-25 | 2019-11-26 | 同济大学 | A kind of active detection method of Chinese herbal medicine |
| CN110501483B (en) * | 2019-07-25 | 2020-12-29 | 同济大学 | Method for detecting activity of Chinese herbal medicine |
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Application publication date: 20140702 |