CN108042545A - Azelastine hydrochloride is preparing the application in inhibiting colon cancer tumours growth drug - Google Patents
Azelastine hydrochloride is preparing the application in inhibiting colon cancer tumours growth drug Download PDFInfo
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- CN108042545A CN108042545A CN201711246087.0A CN201711246087A CN108042545A CN 108042545 A CN108042545 A CN 108042545A CN 201711246087 A CN201711246087 A CN 201711246087A CN 108042545 A CN108042545 A CN 108042545A
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- azelastine hydrochloride
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- colon cancer
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- cancer
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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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- Pharmacology & Pharmacy (AREA)
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Abstract
The invention discloses azelastine hydrochloride as the application for inhibiting colon cancer tumours growth drug.Azelastine hydrochloride is a kind of with 2,3 phthalazinone derivatives, can be used for nettle rash, allergic asthma, allergic rhinitis etc. through FDA approvals, effect is strong and lasting.Azelastine hydrochloride can be used for the growth for inhibiting colon cancer cell in the present invention, notable to the inhibition of tumour growth.Existing anticancer drug is largely expensive, limits the use of drug and with obvious toxic-side effects.Azelastine hydrochloride toxic side effect is small and cheap, overcomes the deficiency of existing drug.And azelastine hydrochloride can be combined with SN38, Oxaliplatin conventional anti-cancer medicines, can significantly increase the inhibition to growth of cancer cells multiplication.
Description
Technical field
The invention belongs to pharmaceutical technology fields, are specially that azelastine hydrochloride is preparing inhibition colon cancer tumours growth drug
In application.
Background technology
Azelastine hydrochloride (Azelastine HCL) is a kind of 2,3 phthalazinone derivatives with new construction, warp
FDA approvals can be used for nettle rash, allergic asthma, allergic rhinitis etc., and effect is strong and lasting.0.05% azelastine hydrochloride
The existing approval production of conventional eye drop solutions, is mainly used for treating and preventing seasonal allergic conjunctivitis.
Cancer is one of most refractory disease in the world.Colon cancer (CRC) occupies second in global mortality of malignant tumors
Position.In China, the colorectal cancer death rate has been located in the 5th.Radiotherapy, chemotherapy etc. are confined to the treatment of intestinal cancer at present.Although it puts
Chemotherapy can inhibit most cancer cell, but can also be killed normal cell while cancer cell is killed, moreover it is possible to cause
The toxic side effects such as gastrointestinal dysfunction, bone marrow suppression greatly reduce the life quality of patient and long-term chemotherapy, malignant tumour
Cell easily generates drug resistance.And the drug for the treatment of cancer is largely at high price, also limits the application of drug.Therefore, seek
It is small to find a kind of toxic side effect, good drug efficacy, low-cost security anticarcinogen are extremely urgent.
Azelastine hydrochloride is in addition to antagonizing histamine effect, and still there are many anti-allergic effects, this product is anti-to causing allergy
The generations of the substances such as the leukotriene and histamine answered, release have inhibition and direct antagonism, can inhibit tentative pant and nose
Allergy and nettle rash etc., effect are strong and lasting.Previously there is activation (such as acidophilus that relevant report azelastine can inhibit inflammatory cell
Property, neutrophilia, basophilla and multinuclear leucocyte and macrophage) medium release (such as leukotriene, the Na-p first different with inhibition
Benzenesulfonyl -1- methyl esters, superoxide anion and platelet activating factor), it reduces acidophil and transfers, significantly reduce ICAM-1 tables
It reaches, it is horizontal to reduce serum acidophilia cationic (ECP).Also there is the anti-inflammatory that document report azelastine can enhance budesonide
Effect.
SN38, Oxaliplatin are traditional anticancer drugs, but it easily causes the drug resistance of cancer cell, and to cancer cell
Proliferation inhibiting effect it is undesirable.If being combined with azelastine hydrochloride, the effect for preferably inhibiting growth of cancer cells can be played.
There has been no articles to show azelastine and cancer cell multiplication side's relation of plane.It there is no report or patent application at present.
The content of the invention
It is an object of the present invention to provide azelastine hydrochlorides to prepare the application in inhibiting colon cancer tumours growth drug.
To achieve the above object, the present invention adopts the following technical scheme that：
Application of the azelastine hydrochloride in inhibition colon cancer tumours growth drug is prepared, the active ingredient of the drug are
Azelastine hydrochloride, chemical structural formula are
Preferably, the drug contains at least one of the azelastine hydrochloride or its pharmaceutical salts.
Preferably, the drug contains pharmaceutical carrier or excipient.
Preferably, the drug is tablet, capsule, dripping pill, electuary or oral liquid.
The purposes of drug the azelastine hydrochloride water dissolution, is administered orally, the dosage (mg/kg) of people=small
Dosage (mg/kg)/(0.0026/20 (g)) of mouse.
The remarkable advantage and advantageous effect of the present invention：
(1) combination of the present invention is outer and experiment in vivo, the results showed that azelastine hydrochloride can inhibit the growth of intestinal cancer, be
The auxiliary treatment of colon cancer cancer provides a kind of new medicament sources.
(2) azelastine hydrochloride is the drug available for diseases such as allergic rhinitis having been approved by, safe, exploitation profit
Prospect is good, cheap, and toxic side effect is small.
(3) azelastine hydrochloride and SN38, Oxaliplatin conventional anti-cancer medicines are combined, can dramatically increased thin to cancer
The inhibition of born of the same parents (Fig. 7-9 is experimental result).
(4) when for taking orally, conventional solid pharmaceutical preparation such as tablet, capsule, liquid preparation, particle can be prepared into
Agent, etc.；During for injecting, parenteral solution can be prepared into.Azelastine hydrochloride can be passed through into intravenous injection or mouth by dosage form
The form of clothes is applied to the patient for needing this treatment.Being applied to the general dosage of patient in need for the treatment of is：The dosage of people
(mg/kg) dosage (mg/kg)/(0.0026/20) (g) of=mouse can also take the circumstances into consideration to change according to age, state of an illness of patient etc..
Description of the drawings
Fig. 1 is the influence result figure that azelastine hydrochloride is proliferated HCT116.
Fig. 2 is the influence result figure that azelastine hydrochloride is proliferated DLD.
Fig. 3 is the influence result figure that azelastine hydrochloride is proliferated HT29.
Fig. 4 is that nude mouse is subendothelial into knurl experimental result picture.
Fig. 5 is the subendothelial quantization experimental result picture into knurl of nude mouse.
Fig. 6 is the change curve of nude mice weight.
Fig. 7 is azelastine hydrochloride and camptothecin derivative (SN38), oxaliplatin (Oxaliplatin) traditional anti-cancer medicine
Internet of Things is with the influence result figure being proliferated to HCT116.
Fig. 8 is azelastine hydrochloride and camptothecin derivative (SN38), oxaliplatin (Oxaliplatin) traditional anti-cancer medicine
Internet of Things is with the influence result figure being proliferated to DLD.
Fig. 9 is azelastine hydrochloride and camptothecin derivative (SN38), oxaliplatin (Oxaliplatin) traditional anti-cancer medicine
Internet of Things is with the influence result figure being proliferated to HT29.
Specific embodiment
With reference to specific embodiment, the present invention is further illustrated.
Embodiment 1
Experiment in vitro
Colon-cancer cell (ATCC, Rockville, the U.S.) is carried out with the azelastine hydrochloride for the various concentration for being dissolved in water
Handle 72 it is small when, then with detection cell Proliferation kit (Beyotime Biotechnology, Chinese Shanghai) carry out
WST-1 experiments detection cytoactive and colony formation1, the azelastine hydrochloride of various concentration is studied to colon-cancer cell
The influence of multiplication.Fig. 1-3 is display Vitro Experimental Results, the results showed that azelastine hydrochloride can inhibit the multiplication of colon-cancer cell.
1.Wang,Y.；Yu,R.Y.；Zhang,J.；Zhang,W.X.；Huang,Z.H.；Hu,H.F.；Li,Y.L.；Li,
B.；He,Q.Y.,Inhibition of Nrf2enhances the anticancer effect of 6-O-
angeloylenolin in lung adenocarcinoma.Biochemical pharmacology 2017,129,43-
53.
Embodiment 2
Experiment in vivo
Choose 21 6 week old, female nude mice (balb/c-nu/nu) is purchased from this Leco Corp. of Shanghai.Control group 7 and
Experimental group 14 builds metastasis models：
(1) every nude mouse need to squeeze into 106A colon cancer cell HT29 (ATCC, Rockville, the U.S.), is resuspended with PBS
Cell HT29 and and matrigel 1:1 mixing obtains that cell is resuspended；
(2) nude mice is anaesthetized before the experiments, by painless and there is pain to stimulate to assess anesthesia level, determine nude mice
In narcosis；
(3) take resuspension cell that nude mice is subcutaneously injected with the micro-syringe of 25G syringe needles, 21 altogether；
(4) colon cancer cell HT29 is squeezed into 21 mouse after a week, starts to be administered with the mode of gavage：By hydrochloric acid nitrogen
Zhuo Siting is dissolved in H2In O, every mouse once feeds 100 μ L.This experiment sets 3 Imperatorin concentration gradients altogether, is respectively
0mg/kg, 10mg/kg and 20mg/kg, each 7, daily medicine feed is once.Size (the measurement shifting of transplantable tumor is measured every three days
The length and width of knurl is planted, and transplantable tumor volume is calculated according to length × wide ^2/2) and nude mice weight.After 2 to 3 weeks, nude mice is pacified
Pleasure is dead and takes out transplantable tumor.
Fig. 4-6 is experiment in vivo result.Fig. 4-5 shows that nude mouse is subendothelial into knurl and its experimental result of quantization.Tumour
Growth curve show colon-cancer cell one-tenth knurl ability be subject to nude mouse subendothelial into knurl apparent inhibition, especially experimental group connecing
When being managed by 20mg/kg azelastine hydrochlorides, reduce 74% compared with control group tumour growth, be significantly suppressed.This example
The bright azelastine hydrochloride of sublist can inhibit the tumour growth of colon cancer.And mouse weight and indifference between three groups are shown in Fig. 6
Not, use not toxic side effect of the azelastine hydrochloride as antitumor drug is illustrated.
Embodiment 3
Experiment in vitro
To the colon-cancer cell azelastine hydrochloride and camptothecin derivative of various concentration (0,2.5,5,10,20,40 μM)
(SN38) (6 μM), oxaliplatin (Oxaliplatin) (10 μM) conventional anti-cancer medicines handle simultaneously cell for 24 hours, 48h, 72h, so
WST-1 experiment detection cytoactive experiments are carried out afterwards, and Fig. 7-9 is display Vitro Experimental Results.The result shows that by hydrochloric acid nitrogen Zhuo Si
Spit of fland and camptothecin derivative (SN38), oxaliplatin (Oxaliplatin) conventional anti-cancer medicines are used in combination can substantially inhibit intestines
The multiplication of cancer cell (HCT116, DLD, HT29).
The implementation of the present invention is not limited to this, and the above according to the invention is known using the ordinary skill of this field
Knowledge and customary means, under the premise of the above-mentioned basic fundamental thought of the present invention is not departed from, the present invention can also make other a variety of shapes
Modification, replacement or the change of formula, all fall within rights protection scope of the present invention.
Claims (4)
1. azelastine hydrochloride inhibits the application of colon cancer tumours growth drug preparing, which is characterized in that the work of the drug
Property ingredient is azelastine hydrochloride, and chemical structural formula is
2. application according to claim 1, which is characterized in that the drug contains the azelastine hydrochloride or its medicine
With at least one of salt.
3. application according to claim 2, which is characterized in that the drug contains pharmaceutical carrier or excipient.
4. application according to claim 3, which is characterized in that the drug is tablet, capsule, dripping pill, electuary or oral
Liquid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711246087.0A CN108042545B (en) | 2017-12-01 | 2017-12-01 | Application of azelastine hydrochloride in preparation of medicine for inhibiting growth of colon cancer tumor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711246087.0A CN108042545B (en) | 2017-12-01 | 2017-12-01 | Application of azelastine hydrochloride in preparation of medicine for inhibiting growth of colon cancer tumor |
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| Publication Number | Publication Date |
|---|---|
| CN108042545A true CN108042545A (en) | 2018-05-18 |
| CN108042545B CN108042545B (en) | 2020-01-17 |
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| CN201711246087.0A Active CN108042545B (en) | 2017-12-01 | 2017-12-01 | Application of azelastine hydrochloride in preparation of medicine for inhibiting growth of colon cancer tumor |
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| CN (1) | CN108042545B (en) |
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2017
- 2017-12-01 CN CN201711246087.0A patent/CN108042545B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| BOSCH-BARRERA J等: "Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy", 《CANCER TREATMENT REVIEWS》 * |
| JOHNSTON PA等: "High-content pSTAT3/1 imaging assays to screen for selective inhibitors of STAT3 pathway activation in head and neck cancer cell lines", 《ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES》 * |
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| CN108042545B (en) | 2020-01-17 |
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