CN110075162A - A kind of combination medicine for treating breast cancer - Google Patents
A kind of combination medicine for treating breast cancer Download PDFInfo
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- CN110075162A CN110075162A CN201910463068.6A CN201910463068A CN110075162A CN 110075162 A CN110075162 A CN 110075162A CN 201910463068 A CN201910463068 A CN 201910463068A CN 110075162 A CN110075162 A CN 110075162A
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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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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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
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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- A—HUMAN NECESSITIES
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- 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
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The present invention provides one kind to the treatment effective combination medicine of breast cancer, contains the first active constituent industrial hemp class compound and the second active constituent artemisine compounds.Industrial hemp class compound and artemisine compounds use in conjunction can be used for preparing anti-tumor drug, and synergistic effect is obvious, have a good application prospect.Patent describes the compositions and preparation method thereof, belong to technical field of pharmaceuticals.
Description
Technical field
The present invention relates to the combination medicine of a kind of class containing industrial hemp compound and artemisine compounds, which is used
Drug can be used for preparing anti-tumor drug, especially be used for the drug of breast cancer treatment.Belong to pharmaceutical technology field.
Background technique
Tumour is a kind of uncontrolled cell proliferation class disease, and reason is complicated, is involved in multiple genetic, epigenetic, cell
And the exception in tissue level.Height variability on genome and apparent gene group level, it is multiple from transcript to albumen etc.
The extreme of biological level is heterogeneous and to the extremely strong adaptability of environment, is the root for the difficult severe that tumour becomes diagnosis and treatment art the most weary
This reason.
Breast cancer (Metastatic breast cancer) is one of most common malignant tumour in the whole world, swollen positioned at women
Tumor disease incidence first, the physical and mental health of women is seriously threatened, wherein in women, male only accounts for 1% for 99% generation in breast cancer.Entirely
Ball breast cancer incidence is in rising trend always since the late 1970s.8, U.S. women just has 1 people trouble in life
Breast cancer.It is unsuitable optimistic although China is not the high-incidence country of breast cancer, the growth rate of China's breast cancer incidence in recent years
But it is higher by high-incidence national 1~2 percentage point.It is announced within 2012 according to National Cancer Center and prevention and control of diseases office, the Ministry of Public Health
Pathogenesis of breast carcinoma data is shown within 2009: national tumour registration area breast cancer incidence occupies the 1st of female malignant,
Female mammary gland cancer morbidity (rough and careless) whole nation adds up to 42.55/10 ten thousand, and city is 51.91/10 ten thousand, and rural area is 23.12/10 ten thousand.
Although mammary gland is not the vitals for maintaining human life activity, breast cancer in situ is simultaneously not fatal；But due to breast cancer cell
The characteristic of normal cell is lost, connection is loose between cell, is easy to fall off.Cancer cell once falls off, and free cancer cell can
To send out whole body with blood or lymph, transfer, threat to life are formed.Breast cancer, which has become, at present threatens women physical and mental health
Kinds of tumor.
The treatment of breast cancer includes the methods of operation, radiotherapy, chemotherapy.Although being continuously improved in early diagnosis and therapy method
With the help of, the prognosis of patient with breast cancer is significantly improved, and still, still has nearly half patient with breast cancer head to examine i.e. at present
Terminal illness state, no healing chance are transferred into for advanced stage or due to recurrence after operation.Thus develop effective, toxic side effect
Lower anti-tumor drug is significant and the urgent need of clinical treatment.
Industrial hemp class compound is extracted from plant industrial hemp flower, leaf and is obtained, containing there are two types of main components: tetrahydro work
Industry cannabinol (THC) and industrial hemp diphenol (CBD).THC (tetrahydro industrial hemp phenol) psychotropic activity is high, Central nervous effect
It is extremely strong；And CBD can hinder influence of the THC to nerve system of human body, not have psychotropic activity and additive, safe tolerance is good.
In addition, CBD also shows the pharmacological activity such as anti-spasm, antianxiety, anti-inflammatory, anticancer, antidepression, in epilepsy, depression, Parkinson
Huge application potential and Industry hemp are shown in the treatment of a variety of diseases such as disease, cancer becomes a kind of important
Bio-pharmaceuticals raw material.
Multinomial in vivo and in vitro finds that industrial hemp class compound shows specific inducing apoptosis of tumour cell, inhibits
The effects such as tumor cell proliferation and growth of transplanted human.Personal use plant industrial hemp class compound is improving cancer disease in recent years
The report that unexpected effect is shown on shape and control cancer progression is also commonplace.Industrial hemp class compound conduct
Anti-tumor drug, and the equal desirable of synergistic effect with traditional tumour therapeutic scheme, such as radiotherapy, chemotherapy.
Qinghaosu extracts isolated one kind from compositae plant artemisia annua (Atemisia annua L.) leaf and contained
The Sesquiterpene lactones compound of oxygen bridge structure is the active drug for the world control malaria prevalence that WHO assert.Due to qinghaosu
In the presence of water-soluble and fat-soluble difference, difficulty is made suitable preparation and causes the problems such as bioavilability is low and re-ignition is high, in qinghaosu
On the basis of derive several common drugs again through chemical improvement, such as dihydroartemisinine, Artemether, arteether, Artesunate.This
A little artemisinin derivatives not only have efficient antimalarial, and low toxicity works the advantages that rapid, also in antitumor, immunosupress such as erythema
Lupus, anti parasitic are anti-inflammatory etc. to achieve compared with good therapeutic effect.Especially in anti-tumor aspect, artemisine chemical combination
Object, which mainly passes through, to be induced cell apoptosis, inhibits the generation of free radical, the effects of angiogenesis is inhibited to play antitumor action.
Industrial hemp class compound is united and applied in tumour with artemisine compounds and explored by the present invention, to widen
The clinical value of industrial hemp class compound and qinghaosu chlorins compound at medicinal aspect.Inventor is sent out by In vivo study
It is existing, the generation and life of the mouse intestinal cancer that industrial hemp class compound joint artemisine compounds can effectively inhibit carcinogen to induce
It is long.It can be seen that industrial hemp class compound and artemisinin derivative are used in combination to be had very in preparation field of antineoplastic medicaments
Good application prospect, can be used for treating cancer.
Summary of the invention
The first aspect of the present invention provides a kind of combination medicine, contains the first active constituent industrial hemp class compound,
With the second active constituent artemisinin derivative or its officinal salt, hydrate, and optional pharmaceutically acceptable auxiliary material.
The second aspect of the present invention provides combination medicine described in first aspect present invention in preparation for treating tumour
And/or the purposes in the drug of prevention tumor recurrence, the especially treatment of breast cancer.
The third aspect of the present invention provides a kind of method for the treatment of and/or pre- preventing tumor, and this method is by therapeutically effective amount
The first active constituent industrial hemp class compound and the second active constituent qinghaosu or derivatives thereof be administered in combination to needs and control
In the individual for the treatment of.Wherein the first active constituent and the second active constituent simultaneously, respectively or are successively administered in need for the treatment of
In body.
In the present invention, the industrial hemp class compound includes 50% or more industrial hemp diphenol (CBD) or its derivative
Object, including and it is not limited only to time industrial hemp diphenol (CBDV) and any medicine for targeting internal industrial hemp element receptor system
Object.
In the present invention, the artemisine compounds are selected from qinghaosu, dihydroartemisinine, Artesunate, Artemether, wormwood artemisia
Ether or its pharmaceutical salt, hydrate, preferably dihydroartemisinine, Artemether, Artesunate.
Combination medicine of the present invention, wherein the molar ratio of the first active constituent and the second active constituent is 100:1
Between~1:100, preferably 20:1~1:20, the molar ratio of preferred first active constituent and the second active constituent is from 5:1
Between~1:5.
Combination medicine of the present invention, wherein the first active constituent industrial hemp class compound with plant extracts,
The combined form of pure compound or both exists.
Combination medicine of the present invention, wherein the first active constituent and the second active constituent are in same preparation unit
In or the first active constituent and the second active constituent respectively in different specification preparation units.
Advantageous effect of the invention
The present invention has carried out industrial hemp class compound, artemisine compounds and the two drug combination respectively and has inhibited breast cancer raw
Long experiment in vivo.The results show that industrial hemp class compound of the present invention and artemisine compounds use in conjunction are shown pair
The coordinate repression of tumour.
Detailed description of the invention
Fig. 1 is CBD and influence of the qinghaosu use in conjunction to nude mice tumor formation；
Fig. 2 is CBD and influence of the Artesunate use in conjunction to nude mice tumor formation；
Fig. 3 is CBD and influence of the dihydroartemisinine use in conjunction to nude mice tumor formation.
Specific embodiment
The present invention is further illustrated below, but the present invention is limited in any way, based on the present invention
It is any made by introduction to transform or replace, it all belongs to the scope of protection of the present invention.
Embodiment 1
The present embodiment provides a kind of injections of pharmaceutical composition for treating breast cancer, operate as follows: weighing Industry hemp
Floral leaf extract 500mg, Artesunate 500mg, add water for injection 200mL, adjust pH value with 8% NaOH solution and make it dissolve；
Sodium chloride 3g is added, 0.2% active carbon is added to boil 15 minutes, filters, filtrate injects water to 1000mL；0.22 μ of medical fluid
The miillpore filter of m filters, and filling 5 bottles, rolls lid, in 110 DEG C pressure sterilizing 40 minutes to get injection type of the invention.
Embodiment 2
The present embodiment provides a kind of dripping pills of pharmaceutical composition for treating breast cancer, operate as follows: weighing Industry cannabis
Leaf extract 50g, Artemether 50g, another taking polyethylene glycol 4000 and appropriate Macrogol 6000 are placed in 80-85 DEG C of water-bath and add
After heat fusing, weighed above two raw material is added, mixes, is kept for 75 DEG C of temperature, instills in atoleine (0-5 DEG C), is made
1000 to get drops of the invention.
Pharmacological experiment
To better illustrate objects and advantages of the present invention, the present invention is by following experiments example to the present invention as antitumor agent
Effect is described, and carcinoma of endometrium can effectively be inhibited by illustrating that industrial hemp class compound and artemisine compounds are used in combination
Tumour growth.The drug dose used in experimental example of the present invention is merely to illustrate technical effect of the invention, not for limitation
Protection scope of the present invention.In experimental example, method therefor unless otherwise instructed, according to normal conditions, conventional method or manufacture
The condition that quotient suggests carries out.Production firm person is not specified in agents useful for same together, is that can buy the normal of acquisition by market
Advise product.
Experimental example 1: the effect of cannabidiol and qinghaosu use in conjunction to endometrial cancer cell growth in nude mouse
1. experimental material
1) reagent: after CBD (Sigma, St. Louis, MO, USA) is dissolved with ethyl alcohol, with normal saline at 1mg/ml
Solution, 4 degree of preservations；Qinghaosu (ART) and its derivative dihydroartemisinine (DHA), Artesunate (ARS) are purchased from purchased from wheat
Crin biochemical technology Co., Ltd, Chinese Shanghai (are purchased from Sigma-Aldrich with 4 degree of 1% methylcellulose refrigerated respectively
Company, Chinese Shanghai) solution dissolution be configured to corresponding solution, it is ready-to-use.
2) cell: human breast cancer cell MDA-MB-231.
3) Female nude mice, 4-5 week old.
2. experimental group
1) control group: nude mice is handled using isometric drug solvent
2) CBD treatment group: CBD 60mg/kg, intraperitoneal injection, once a day
3) ART treatment group: ART 60mg/kg, stomach-filling, once a day
4) CBD+ART treatment group: CBD 30mg/kg, intraperitoneal injection, while ART 30mg/kg, stomach-filling, once a day
3. nude mice by subcutaneous Tumorigenesis
Breast cancer lines MDA-MB-231 cell is containing 10% FBS, 100 U/ml penicillin, 100g/ml strepto-
It is cultivated under conditions of 37 DEG C, 5% CO2 in the culture medium DMEM of element, every 3~4 d passage is primary, takes logarithmic growth
The cell of phase, and concentration is adjusted to 2 × 107/ml, single cell suspension is collected, it is outstanding to extract cell using l ml syringe
0.2 ml of liquid, it is subcutaneous to be injected into mice belly side to the right, establishes tumor model.Nude mice tumor formation situation is observed, and measures subcutaneous tumors
Longest diameter (L) and shortest diameter (S), to gross tumor volume (V=L × S2/ 2) reach 100mm3Afterwards, start to treat according to grouping.Every 3
Its nude mouse tumor volume of measurement, put to death animal after 4 weeks.
4. experimental result
As a result as shown in Fig. 1, each treatment group (n=5) gross tumor volume is obviously reduced than control group, shows CBD and qinghaosu list medicine
The growth that can effectively inhibit breast cancer has significant curative effect to breast cancer, and the tool of the growth to tumour is used in combination in two medicines
There is more significant inhibitory effect.
Experimental example 2: the effect of cannabidiol and Artesunate use in conjunction to breast cancer cell growth in nude mouse
Experimental method and dosage are the same, and as a result as shown in Fig. 2, each treatment group (n=5) gross tumor volume is obviously reduced than control group,
The growth of carcinoma of endometrium can effectively be inhibited by showing CBD and Artesunate list medicine, have significant curative effect, and two to breast cancer
The growth to tumour is used in combination with more significant inhibitory effect in medicine.
Experimental example 3: the work of cannabidiol and dihydroartemisinine use in conjunction to endometrial cancer cell growth in nude mouse
With.
Experimental method and dosage are the same, and as a result as shown in Fig. 3, each treatment group (n=5) gross tumor volume is more obvious than control group
It reduces, the growth of breast cancer can effectively be inhibited by showing CBD and dihydroartemisinine list medicine, there is significant curative effect to breast cancer,
And two medicine the growth to tumour is used in combination with more significant inhibitory effect.
Pharmacological experiment is summarized: being better than industrial hemp with dosage industrial hemp diphenol+artemisinin-based drug processing group result
Diphenol drug-treated group, artemisinin-based drug processing group, it was demonstrated that industrial hemp diphenol and the combination of qinghaosu medicine series play
Unexpected synergy.
Claims (11)
1. the drug combination of a kind of industrial hemp class compound and artemisine compounds is in treatment of solid tumor drug, especially
Application in breast cancer treatment drug.
2. application as described in claim 1, affiliated pharmaceutical composition includes the first active constituent at least one industrial hemp class
Compound or derivatives thereof and a kind of artemisine compounds of the second active constituent and optional pharmaceutically acceptable carrier
Or excipient.
3., wherein the first active constituent is industrial hemp class compound, at least being wrapped such as combination medicine claimed in claims 1-2
Include 50% or more cannabidiol (CBD) or derivatives thereof.
4. wherein artemisine compounds are a effective amount of qinghaosu, double hydrogen blueness such as pharmaceutical composition claimed in claims 1-2
Artemisin, Artesunate, Artemether, arteether or its officinal salt, hydrate be one such or several mixtures.
5. the pharmaceutical composition as described in claim 1-4, wherein the molar ratio of the first active constituent and the second active constituent is
100:1 to 1:100.
6. the pharmaceutical composition as described in claim 1-4, wherein the molar ratio of the first active constituent and the second active constituent is
20:1 to 1:20.
7. such as the combination medicine of any one of claim 1-4, wherein the first active constituent and the second active constituent are same
In preparation unit or the first active constituent and the second active constituent are respectively in different specification preparation units.
8. combination medicine according to any one of claims 1-4 is controlling applied to treatment of cancer, especially breast cancer
It treats.
9. the combination medicine as described in claim 1-4, which is characterized in that the drug is oral preparation or ejection preparation；
Preferably, the oral preparation is selected from tablet, capsule, soft capsule, granule, suspension, dripping pill, pill, liquid oral
One of preparation；Preferably, the tablet is conventional tablet, dispersible tablet, oral disnitegration tablet or sustained release tablets；Preferably, described
Ejection preparation is injection or powder-injection.
10. the combination medicine as described in claim 1-4, wherein the first effective component industrial hemp class compound is mentioned with plant
The composition forms of object, pure compound or both are taken to exist.
11. in application described in any of the above-described claim, wherein industrial hemp class compound and artemisine compounds that
This distinguishes, is serially or simultaneously administered.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910463068.6A CN110075162A (en) | 2019-05-30 | 2019-05-30 | A kind of combination medicine for treating breast cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910463068.6A CN110075162A (en) | 2019-05-30 | 2019-05-30 | A kind of combination medicine for treating breast cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110075162A true CN110075162A (en) | 2019-08-02 |
Family
ID=67422642
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910463068.6A Withdrawn CN110075162A (en) | 2019-05-30 | 2019-05-30 | A kind of combination medicine for treating breast cancer |
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| CN (1) | CN110075162A (en) |
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2019
- 2019-05-30 CN CN201910463068.6A patent/CN110075162A/en not_active Withdrawn
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| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| CB02 | Change of applicant information | ||
| CB02 | Change of applicant information |
Address after: No. 300, Southwest Forestry University, Panlong District, Kunming, Yunnan 650224 Applicant after: Luan Yunpeng Address before: 650000 No. 141 Chunyu Road, Wuhua District, Kunming City, Yunnan Province Applicant before: Luan Yunpeng |
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| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20190802 |