CN110063988A - A kind of pharmaceutical composition and preparation method thereof for treating neuroblastoma - Google Patents
A kind of pharmaceutical composition and preparation method thereof for treating neuroblastoma Download PDFInfo
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- CN110063988A CN110063988A CN201910505679.2A CN201910505679A CN110063988A CN 110063988 A CN110063988 A CN 110063988A CN 201910505679 A CN201910505679 A CN 201910505679A CN 110063988 A CN110063988 A CN 110063988A
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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
- A61K31/365—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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- 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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Abstract
The present invention provides one kind to the treatment effective combination medicine of neuroblastoma, contains the first active constituent industrial hemp floral leaf extract and the second active constituent artemisine compounds.Industrial hemp floral leaf extract and artemisine compounds use in conjunction can be used for preparing anti-tumor drug, and unexpected synergy is especially played in the treatment of neuroblastoma, is had a good application prospect.Patent describes the pharmaceutical compositions and preparation method thereof, belong to pharmaceutical field.
Description
Technical field
The present invention relates to the combination medicine of a kind of floral leaf containing industrial hemp extract and artemisine compounds, the joints
With the therapeutic agent that drug is for neuroblastoma.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.
Neuroblastoma (NB) is the tumour being made of undifferentiated neuroblast, is outside the most common cranium of children
Solid tumor, the disease incidence in pediatric tumor are 6%~10%, account for the 10%~15% of childhood cancer death toll.For 4 years old with
Lower children, the death rate of each a population of one million are 10；For 4-9 years old children, the death rate of each a population of one million was 4.Nerve
Blastoma belongs to neuroendocrine, can be originating from any neural spine position of stomodaeal nervous system.Its is most common
Happening part be adrenal gland, but the nerve fiber in neck, chest, abdomen and pelvic cavity can also occur.Neuroblast
The treatment of tumor includes the methods of operation, radiotherapy, chemotherapy.Although with the help of early diagnosis and therapy method is continuously improved, mind
Prognosis through blastoma patient is significantly improved, and still, still has nearly half neuroblastoma patient head to examine at present
As advanced stage or since recurrence after operation is transferred into terminal illness state, no healing chance.Thus develop effective, malicious secondary work
With lower anti-tumor drug is significant and the urgent need of clinical treatment.
Industrial hemp floral leaf extract is extracted from cannabis plant flower, leaf and is obtained, containing there are two types of main components: tetrahydro hemp
Phenol (THC) and cannabidiol (CBD).THC (tetrahydrocannabinol) psychotropic activity is high, and it is that drugs are big that Central nervous effect is extremely strong
The major toxicity ingredient of fiber crops;And CBD can hinder influence of the THC to nerve system of human body, not have psychotropic activity and additive, peace
Full tolerance is good.In addition, CBD also shows the pharmacological activity such as anti-spasm, antianxiety, anti-inflammatory, anticancer, antidepression, in epilepsy, suppression
Huge application potential and industrial hemp are shown in the treatment of a variety of diseases such as strongly fragrant, parkinsonism, cancer becomes one kind
Important bio-pharmaceuticals raw material.
Qinghaosu in compositae plant chrysanthemum mugwort from extracting in a kind of isolated sequiterpene containing peroxide bridge structure
Ester type compound is the active drug for the world control malaria prevalence that WHO assert.Since qinghaosu is in the presence of water-soluble and fat-soluble
Difference, difficulty are made suitable preparation and cause the problems such as bioavilability is low and re-ignition is high, on the basis of qinghaosu again through chemical improvement
Several common drugs are derived, such as dihydroartemisinine, Artemether, arteether, Artesunate.These artemisinin derivatives are not only
With efficient antimalarial, low toxicity works the advantages that rapid, also in antitumor, immunosupress such as lupus erythematosus, anti parasitic is anti-inflammatory
Etc. achieve compared with good therapeutic effect.Artemisine compounds, which mainly pass through, inhibits the generation of free radical to play anti-nerve
The effect of blastoma.
Industrial hemp floral leaf extract and artemisine compounds are united and applied in neuroblastoma and carried out by the present invention
It explores, to widen industrial hemp floral leaf extract and qinghaosu chlorins compound in the clinical value of medicinal aspect.Inventor is logical
Pharmacodynamic study discovery is crossed, industrial hemp floral leaf extract joint artemisine compounds can effectively inhibit tumour growth, especially
It is neuroblastoma.It can be seen that industrial hemp floral leaf extract and artemisinin derivatives are used in combination and are preparing anti-mind
It is had a good application prospect through blastoma field.
Summary of the invention
The first aspect of the present invention provides a kind of combination medicine, extracts containing the first active constituent industrial hemp floral leaf
Object and the second active constituent artemisinin derivative or its officinal salt, hydrate, and optional pharmaceutically acceptable auxiliary material.
The second aspect of the present invention provide first aspect present invention described in combination medicine preparation for treat and/or
Prevent the purposes in neuroblast tumor medicine.
The third aspect of the present invention provides a kind of method treated and/or prevent neuroblastoma, and this method is will to control
It treats a effective amount of first active constituent industrial hemp floral leaf extract and the second active constituent artemisinin derivatives is administered in combination
Into individual in need for the treatment of.Wherein the first active constituent and the second active constituent simultaneously, respectively or are successively administered to needs
In the individual for the treatment of.
Wherein the first active constituent is industrial hemp floral leaf extract, cannabidiol (CBD) including at least 50% or more or
Its derivative, such as cannabidivarin (CBDV) etc..
Wherein the second active constituent is artemisine compounds, preferably a effective amount of qinghaosu, dihydroartemisinine, sweet wormwood amber
Ester, Artemether, arteether or its officinal salt, hydrate.
Wherein the molar ratio of the first active constituent and the second active constituent is 99.9:0.1 to 0.1:99.9.
Further, the molar ratio of the first active constituent and the second active constituent is between 20:1~1:20, and preferred
The molar ratio of one active constituent and the second active constituent is between 5:1~1:5.
Wherein the first active constituent and the second active constituent are in same preparation unit or the first active constituent and
Two active constituents are respectively in different specification preparation units.
Wherein affiliated drug is oral preparation or ejection preparation；Preferably, the oral preparation be selected from tablet, capsule,
One of soft capsule, granule, suspension, dripping pill, pill, oral liquid；Preferably, the tablet is ordinary tablet
Agent, dispersible tablet, oral disnitegration tablet or sustained release tablets；Preferably, the ejection preparation is injection or powder-injection.
Wherein the first effective component industrial hemp floral leaf extract is with the combination of plant extracts, pure compound or both
Object form exists.
Advantageous effect of the invention
The present invention has carried out industrial hemp floral leaf extract and artemisine compounds combination therapy neuroblastoma respectively
Pharmacodynamic experiment.The results show that industrial hemp floral leaf extract of the present invention and artemisine compounds use in conjunction are shown pair
The synergistic therapeutic action of neuroblastoma.
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 made it is any transform or replace, all belong to the scope of protection of the present invention.
Embodiment 1
The present embodiment provides a kind of injections of pharmaceutical composition for treating neuroblastoma, operate as follows: weighing industrial big
Fried dough twist leaf extract 500mg, Artesunate 500mg, add water for injection 200mL, and adjusting pH value with 8% NaOH solution keeps its molten
Solution；Sodium chloride 3g is added, 0.2% active carbon is added to boil 15 minutes, filters, filtrate injects water to 1000mL；Medical fluid is used
0.22 μm miillpore filter filtration, filling 5 bottles, roll 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 neuroblastoma, operate as follows: weighing industrial hemp
Floral leaf extract 50g, Artemether 40g, another taking polyethylene glycol 4000 and appropriate Macrogol 6000, are placed in 80-85 DEG C of water-bath
After heating melting, weighed above two raw material is added, mixes, is kept for 75 DEG C of temperature, instills in atoleine (0-5 DEG C), system
At 1000 to get drops of the invention.
Pharmacodynamic 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 neural mother can effectively be treated carefully by illustrating that industrial hemp floral leaf extract and artemisine compounds are used in combination
Born of the same parents' tumor.The drug dose used in experimental example of the present invention is merely to illustrate technical effect of the invention, not for limiting this hair
Bright protection scope.In experimental example, unless otherwise instructed, according to normal conditions, conventional method or manufacturer build method therefor
The condition of view carries out.Production firm person is not specified in agents useful for same together, is the conventional production that can be bought and be obtained by market
Product.
Subordinate list explanation
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
Experimental example 1: the effect of cannabidiol and qinghaosu use in conjunction to neuroblastoma 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 (ATS) 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 neuroblastoma cells SH-SY5Y
3) Female nude mice, 4-6 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
The SH-SY5Y cell of logarithmic phase growth is taken, is counted after PBS centrifuge washing 2 times, adjustment cell density is 2 × 107
/mL.By the cell suspension inoculation of adjustment to nude mice dorsal sc, every 0.2 mL, sterile working.Nude mice tumor formation situation is observed,
And the longest diameter (L) and shortest diameter (S) of subcutaneous tumors are measured, to gross tumor volume (V=L × S2/ 2) reach 100mm3Afterwards, according to grouping
Start to treat.The nude mouse tumor volume of measurement in every 3 days, 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 neuroblastoma has significant curative effect to neuroblastoma, and two medicines are used in combination pair
The growth of tumour has more significant inhibitory effect.
Experimental example 2: the work that cannabidiol and Artesunate use in conjunction grow neuroblastoma cell in nude mouse
With
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 neuroblastoma can effectively be inhibited by showing CBD and Artesunate list medicine, be had to neuroblastoma significant
Curative effect, and the growth to tumour is used in combination with more significant inhibitory effect in two medicines.
Experimental example 3: cannabidiol and dihydroartemisinine use in conjunction are to neuroblastoma cell growth in nude mouse
Effect
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 obviously reduced than control group,
The growth of neuroblastoma can effectively be inhibited by showing CBD and dihydroartemisinine list medicine, be had to neuroblastoma significant
Curative effect, and the growth to tumour is used in combination with more significant inhibitory effect in two medicines.
Pharmacological experiment is summarized: being better than cannabidiol drug with dosage cannabidiol+artemisinin-based drug processing group result
Processing group, artemisinin-based drug processing group, it was demonstrated that cannabidiol and the combination of qinghaosu medicine series are in treatment neuroblastoma
Aspect plays unexpected synergy.
Claims (11)
1. the drug combination of a kind of industrial hemp floral leaf extract and artemisine compounds is in the medicine of neuroblastoma
Application in object.
2. application as described in claim 1, affiliated pharmaceutical composition include at least one industrial hemp floral leaf extract or its
Derivative and a kind of artemisine compounds and optional pharmaceutically acceptable carrier or excipient.
3. such as combination medicine claimed in claims 1-2, it is characterised in that: wherein the first active constituent is industrial hemp floral leaf
Extract, including at least 50% or more cannabidiol (CBD) or derivatives thereof.
4. such as pharmaceutical composition claimed in claims 1-2, it is characterised in that: wherein the second active constituent is artemisine chemical combination
Object, preferably a effective amount of qinghaosu, dihydroartemisinine, Artesunate, Artemether, arteether or its officinal salt, hydrate.
5. the pharmaceutical composition as described in claim 1-4, it is characterised in that: wherein the first active constituent and the second active constituent
Molar ratio be 99.9:0.1 to 0.1:99.9.
6. the pharmaceutical composition as described in claim 1-4, it is characterised in that: wherein the first active constituent and the second active constituent
Molar ratio be 20:1 to 1:20.
7. such as the combination medicine of any one of claim 1-6, it is characterised in that: wherein the first active constituent and the second activity at
Point in same preparation unit or the first active constituent and the second active constituent are respectively in different specification preparation units
In.
8. being the treatment applied to neuroblastoma such as the described in any item combination medicines of claim 1-7.
9. the combination medicine as described in claim 1-7, it is characterised in that: affiliated 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. combination medicine as claimed in claims 1-9, it is characterised in that: wherein the first effective component industrial hemp floral leaf
Extract exists with the composition forms of plant extracts, pure compound or both.
11. in application described in any of the above-described claim, it is characterised in that: wherein industrial hemp floral leaf extract and sweet wormwood
Chlorins compound separately from each other, is serially or simultaneously administered.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910505679.2A CN110063988A (en) | 2019-06-12 | 2019-06-12 | A kind of pharmaceutical composition and preparation method thereof for treating neuroblastoma |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910505679.2A CN110063988A (en) | 2019-06-12 | 2019-06-12 | A kind of pharmaceutical composition and preparation method thereof for treating neuroblastoma |
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| CN110063988A true CN110063988A (en) | 2019-07-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201910505679.2A Withdrawn CN110063988A (en) | 2019-06-12 | 2019-06-12 | A kind of pharmaceutical composition and preparation method thereof for treating neuroblastoma |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114099684A (en) * | 2022-01-25 | 2022-03-01 | 中国中医科学院中药研究所 | Application of miR-32-5p in preparation of medicine for improving sensitivity of tumor cells to dihydroartemisinin |
-
2019
- 2019-06-12 CN CN201910505679.2A patent/CN110063988A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114099684A (en) * | 2022-01-25 | 2022-03-01 | 中国中医科学院中药研究所 | Application of miR-32-5p in preparation of medicine for improving sensitivity of tumor cells to dihydroartemisinin |
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| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20190730 |
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| WW01 | Invention patent application withdrawn after publication |