CN107456456A - The purposes of Irinotecan or its officinal salt in the medicine for preparing treatment breast cancer - Google Patents
The purposes of Irinotecan or its officinal salt in the medicine for preparing treatment breast cancer Download PDFInfo
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- CN107456456A CN107456456A CN201710408211.2A CN201710408211A CN107456456A CN 107456456 A CN107456456 A CN 107456456A CN 201710408211 A CN201710408211 A CN 201710408211A CN 107456456 A CN107456456 A CN 107456456A
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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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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Abstract
The present invention relates to the purposes of Irinotecan or its officinal salt in the medicine for preparing treatment breast cancer.Specifically, the purposes the present invention relates to irinotecan liposome in the medicine for preparing treatment breast cancer.
Description
Technical field
The present invention relates to the purposes of Irinotecan or its officinal salt in the medicine for preparing treatment breast cancer.
Background technology
Breast cancer is one of most common malignant tumour of women, has the incidence of disease high, has much invasion, but course advancement delays
Slowly, Chinese population association 2010 year 2 month issues in Beijing on the 1st《Chinese mammary gland disease survey report》, report display, China city
The death rate of city area breast cancer increases 38.91%, and breast cancer, which has become, threatens WomanHealth maximum disease, at present
In at least 156 kinds of the breast cancer medicines for grinding and listing, wherein 68% is target therapeutic agent.
Irinotecan is the semi-synthetic derivative of camptothecine.Camptothecine can be combined specifically with topoisomerase I, the latter
Inducing reversible single-strand is broken, so that DNA double chain structure is untwisted；Irinotecan and its active metabolite SN-38 can be with topologys
Isomerase I-DNA compounds combine, so as to prevent to be broken single-stranded reconnection.Existing research prompting, the cell toxicant of Irinotecan
Effect is attributed in DNA building-up processes, replicase and the compound phase of topoisomerase I-DNA- Irinotecans (or SN-38) three
Interaction, so as to cause DNA double chain to be broken.
At present, Irinotecan is clinically mainly used in the treatment of late stage colorectal cancer patients.Although there is Irinotecan to be used for
Other cancers are treated, or the report for the treatment of breast cancer is used in combination with other medicines for Irinotecan, but do not find that Yi Li is replaced
Health, which is used alone, can treat breast cancer.Particularly BEACON researchs (NCT01492101) use the length after Irinotecan improvement
Effect topoisomerase enzyme inhibitor Etirinotecan Pegol are used to more than the two wires of advanced breast cancer treat not bring existence
Benefit.
CN103120645A and CN102271659A discloses a kind of irinotecan liposome composition and preparation method thereof,
And confirm that it has good inhibiting effect to human colon carcinoma Ls-174 cells, but the document is also not disclosed irinotecan liposome and used
In the purposes for the treatment of breast cancer.
The content of the invention
The present invention is it has surprisingly been found that Irinotecan or its officinal salt can be used in treating breast cancer, and achieve good
The effect of good.
Therefore, the purposes the invention provides Irinotecan or its salt in the medicine for preparing treatment breast cancer.Preferably,
Wherein described Irinotecan or its officinal salt are used alone, i.e., need not be used in combination with other medicines can produce it is good
The effect of good.
In a preferred embodiment of the present invention, described Irinotecan or its salt are applied in the form of liposome.It is preferred that
Irinotecan liposome contain Irinotecan or its salt, neutral phospholipid and cholesterol, wherein the cholesterol and neutral phosphor
The weight ratio of fat is 1：3~5, preferably 1：3.5~4.5, most preferably 1：4.
The weight ratio of Irinotecan or itself and neutral phosphine fat is 1：2~5, preferably 1：2.5-4 most preferably 1：4.
In preferred embodiments, the neutral phospholipid is selected from HSPC, phosphatidyl-ethanolamine, ovum
One or more in phosphatide, cuorin, preferably hydrogenated soya phosphatide.
In preferred embodiments, the liposome also lipid derivate containing hydrophilic macromolecule, is preferably trained
Change phosphatidyl-ethanolamine DSPE-PEG2000。
In the present invention, described breast cancer can be advanced breast cancer, such as can be metastatic breast cancer.The present invention
Patient with breast cancer can be including chemotherapy, radiotherapy, endocrine or the patient of targeted therapy failure by systematic treating, herein
Endodontic failure refers to that disease cannot control after these are treated, and continue to the situation of progress.What these patients were received
Systematic treating can be treated by the one or more in the various conventional medicines in this area.Wherein described chemotherapy can be with
It is to use various conventional chemotherapeutic drug therapies, such as anthracycline (includes but is not limited to Doxorubicin, epirubicin, how soft ratio
Star liposome)；Japanese yew class (includes but is not limited to taxol, docetaxel, albumin combination type taxol)；Anti-metabolism (bag
Include but be not limited to capecitabine, gemcitabine)；Microtubule inhibitors class (includes but is not limited to vinorelbine, vinflunine, Ai
Bu Lin)；And other chemotherapeutics for being not belonging to above-mentioned classification (include but is not limited to endoxan, mitoxantrone, cis-platinum, card
Platinum, Etoposide, vinblastine, fluorouracil, oxaliplatin, tegafur, gimeracil and oteracil potassium, Ipsapirone).Described endocrine therapy is made
Medicine include but is not limited to Anastrozole, Letrozole, Exemestane, fulvestrant, everolimus, Palbociclib, he
Not former times sweet smell, Toremifene, megestrol acetate, Medroxyprogesterone, ethinylestradiol, Fluoxymesterone etc..Described targeted therapy can
With use a variety of targeted drugs, such as HER2 inhibitor (include but is not limited to Herceptin, handkerchief trastuzumab, Lapatinib,
HKI-272 etc.)；Angiogenesis inhibitors (include but is not limited to bevacizumab, match cut down pearl monoclonal antibody, relax cloth for Buddhist nun, Ah pa for Buddhist nun,
Sutent, Lucentis, ramucirumab etc.)；EGFR inhibitor (include but is not limited to Gefitinib, Tarceva or angstrom
Gram replace Buddhist nun)；And other targeted drugs, such as Sorafenib etc..
In the present invention, described Irinotecan or its salt and their liposome, in terms of irinotecan hydrochloride, with 40
~200mg/m2Dosage apply, preferably with 80~120mg/m2Dosage apply, more preferably 100~120mg/m2, most preferably with
100mg/m2Dosage apply.Each breast cancer patients are according to the every three Mondays dosage period of preceding doses, each cycle administration
Once.
By the clinical test of reality, it was demonstrated that Irinotecan or its salt, it is right particularly when being administered in the form of liposome
There is the effect of fine in breast cancer patients, and toxic side effect is in the range of can bearing.
Embodiment
It is used to further describe the present invention with reference to embodiments, but these embodiments are not intended to limit the scope of the invention.
Trial drug and dosage regimen：Yi Li is prepared into according to method disclosed in CN103120645A according to prescription in following table to replace
Health liposome freeze-drying powder injection.
Table 1：Irinotecan liposome prescription
Note：A 40mg dosages are with the irinotecan hydrochloride (C without the crystallization water33H38N4O6HCl) count, base in b finished products
This removal, removing substantially in c finished products, d is conversion AMSP dosage, is actually used as sodium dihydrogen phosphate-water,
Because irinotecan hydrochloride has the crystallization water, and there is about 8% loss after feeding intake, according to irinotecan hydrochloride when actually feeding intake：Hydrogenation
Soy phosphatidylcholine phatidylcholine=3:10 ratio feeds intake.
Embodiment 1：The clinical test of one irinotecan liposome treatment breast cancer
Test method：Irinotecan liposome is diluted using the sodium chloride injections of 250ml 0.9%, then vein drips
Note, 90 ± 5min is interior to be completed to instil.Every 3 Monday dosage period, each cycle are administered once.The medicine-feeding test in 2 cycles terminates
Afterwards, curative effect is evaluated by RECIST1.1 standards, first evaluation CR, PR, SD subject can continue to receive controlling for same scheme
Treat, first evaluation CR, PR subject carry out curative effect confirmation in 4 weeks after evaluating first.
By on March 3rd, 2017 breast cancer enter group 15, that completes therapeutic evaluation has 11, wherein 5 PR
(45.4%), 3 SD (27.3%), 3 PD (27.3%), i.e. ORR (objective remission rate) are 45.4%, DCR (disease controls
Rate) it is 72.7%.Still there is 0 in group medication at present.For advanced breast cancer patient, irinotecan liposome is in 100mg/
m2And 120mg/m2Security, tolerance are good, clinical controllable, and antitumor curative effect is notable.
Patient's details such as following table of existing curative effect evaluation.Wherein, the implication of each english abbreviation is as follows.
PD：Progression of disease, diameter and minimum value increase at least 20% than target focus diameter sum and diameter sum it is absolute
(there are one or more new focuses and is also considered as progression of disease) in value increase at least 5mm；SD：Stable disease, target focus maximum diameter it
PR is not reached with reducing, or increase does not reach PD PR：Part is alleviated, and target focus diameter sum reduces at least 30% than baseline values, extremely
Maintain 4 weeks less.ER:ERs.PR:Progesterone receptor.HER-2:Human epidermal growth factor receptor 2.C is cycle English
Write a Chinese character in simplified form, represent the test period.
Claims (19)
1. the purposes of Irinotecan or its officinal salt in the medicine for preparing treatment breast cancer, described officinal salt are preferably
Hydrochloride.
2. purposes according to claim 1, wherein described Irinotecan or its officinal salt are used alone.
3. purposes according to claim 1, wherein described Irinotecan or its its officinal salt are in the form of liposome
Using.
4. purposes according to claim 2, wherein described irinotecan liposome contains Irinotecan or its is pharmaceutically acceptable
Salt, neutral phospholipid and cholesterol.
5. purposes according to claim 4, wherein the weight of the cholesterol and neutral phospholipid ratio is 1：3~5, preferably 1：
3.5~4.5, most preferably 1：4.
6. purposes according to claim 4, wherein the weight of described Irinotecan or its officinal salt and neutral phosphine fat
Than for 1：2~5, preferably 1：2.5-4 most preferably 1：4.
7. purposes according to claim 4, wherein the neutral phospholipid is selected from HSPC, phosphatidyl second
One or more in hydramine, lecithin, cuorin, preferably hydrogenated soya phosphatide.
8. purposes according to claim 4, wherein, the liposome also lipid derivate containing hydrophilic macromolecule,
Preferably trainingization phosphatidyl-ethanolamine DSPE-PEG2000。
9. purposes according to claim 1, wherein the breast cancer is advanced breast cancer.
10. purposes according to claim 1, wherein the breast cancer is metastatic breast cancer.
11. purposes according to claim 1, wherein the breast cancer be HER-2 positive breast cancers or PR it is positive or
Person ER positive breast cancers or three cloudy breast cancer.
12. purposes according to claim 1, wherein the breast cancer is by selected from chemotherapy, radiotherapy, endocrine or targeting
The breast cancer continued to progress from after the treatment means for the treatment of.
13. purposes according to claim 12, wherein described chemotherapy is to use such as anthracycline, Japanese yew class, antimetabolic
The chemotherapy that class microtubule inhibitors class medicine is carried out.
14. purposes according to claim 12, wherein described chemotherapy is used selected from endoxan, mitoxantrone, suitable
The chemotherapy that platinum, carboplatin, Etoposide, vinblastine, fluorouracil, oxaliplatin, the medicine of tegafur, gimeracil and oteracil potassium and Ipsapirone are carried out.
15. purposes according to claim 13, wherein described anthracene nucleus medicament is selected from Doxorubicin, epirubicin, more
It is soft than star liposome；Described Taxane family is selected from taxol, docetaxel, albumin combination type taxol；Described is anti-
It is metabolized class medicine and is selected from capecitabine, gemcitabine；Described microtubule inhibitors class medicine be selected from vinorelbine, vinflunine,
Eribulin.
16. purposes according to claim 12, wherein medicine used in described endocrine therapy be selected from Anastrozole,
Letrozole, Exemestane, fulvestrant, everolimus, Palbociclib, TAM, Toremifene, megestrol acetate,
One or more in Medroxyprogesterone, ethinylestradiol, Fluoxymesterone.
17. purposes according to claim 12, wherein described targeted therapy is selected from HER2 inhibitor, Agiogenesis inhibition
Agent and the targeted drug of EGFR inhibitor.
18. purposes according to claim 17, wherein described HER2 inhibitor is selected from the appropriate pearl list of Herceptin, pa
Anti-, Lapatinib, HKI-272；Described angiogenesis inhibitors be selected from bevacizumab, match cut down pearl monoclonal antibody, relax cloth for Buddhist nun, Ah
Pa is for Buddhist nun, Sutent, Lucentis, ramucirumab；Described EGFR inhibitor be selected from Gefitinib, Tarceva and
Conmana.
19. purposes according to claim 1, wherein described Irinotecan or its officinal salt and their lipid
Body, in terms of irinotecan hydrochloride, with 40~200mg/m2Dosage apply, preferably with 80~120mg/m2Dosage apply, it is more excellent
Select 100~120mg/m2, most preferably with 100mg/m2Dosage apply.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2016103889346 | 2016-06-03 | ||
| CN201610388934 | 2016-06-03 |
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| Publication Number | Publication Date |
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| CN107456456A true CN107456456A (en) | 2017-12-12 |
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| CN201710408211.2A Pending CN107456456A (en) | 2016-06-03 | 2017-06-02 | The purposes of Irinotecan or its officinal salt in the medicine for preparing treatment breast cancer |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110433167A (en) * | 2019-03-06 | 2019-11-12 | 武汉百药联科科技有限公司 | A kind of pharmaceutical composition and its application in preparation treatment breast cancer medicines |
Citations (4)
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|---|---|---|---|---|
| CN1774249A (en) * | 2003-04-28 | 2006-05-17 | 法玛西雅厄普约翰有限责任公司 | Use of irinotecan for treatment of resistant breast cancer |
| CN103120645A (en) * | 2009-12-03 | 2013-05-29 | 江苏恒瑞医药股份有限公司 | Irinotecan or irinotecan hydrochloride lipidosome and preparation method thereof |
| CN102271659B (en) * | 2009-12-03 | 2013-09-18 | 江苏恒瑞医药股份有限公司 | Liposome of irinotecan or its hydrochloride and preparation method thereof |
| CN104906586A (en) * | 2014-03-10 | 2015-09-16 | 中国科学院上海药物研究所 | Irinotecan hydrochloride composite phospholipid composition, preparation method and applications thereof |
-
2017
- 2017-06-02 CN CN201710408211.2A patent/CN107456456A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1774249A (en) * | 2003-04-28 | 2006-05-17 | 法玛西雅厄普约翰有限责任公司 | Use of irinotecan for treatment of resistant breast cancer |
| CN103120645A (en) * | 2009-12-03 | 2013-05-29 | 江苏恒瑞医药股份有限公司 | Irinotecan or irinotecan hydrochloride lipidosome and preparation method thereof |
| CN102271659B (en) * | 2009-12-03 | 2013-09-18 | 江苏恒瑞医药股份有限公司 | Liposome of irinotecan or its hydrochloride and preparation method thereof |
| CN104906586A (en) * | 2014-03-10 | 2015-09-16 | 中国科学院上海药物研究所 | Irinotecan hydrochloride composite phospholipid composition, preparation method and applications thereof |
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| 刘圣等主编: "《静脉用药物调配技术》", 31 January 2015 * |
| 陈果等: "伊立替康长循环脂质体的初步生物学活性研究", 《中国现代医学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110433167A (en) * | 2019-03-06 | 2019-11-12 | 武汉百药联科科技有限公司 | A kind of pharmaceutical composition and its application in preparation treatment breast cancer medicines |
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