CN110063990A - A kind of pharmaceutical composition and preparation method thereof for treating lymph cancer - Google Patents
A kind of pharmaceutical composition and preparation method thereof for treating lymph cancer Download PDFInfo
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- CN110063990A CN110063990A CN201910506125.4A CN201910506125A CN110063990A CN 110063990 A CN110063990 A CN 110063990A CN 201910506125 A CN201910506125 A CN 201910506125A CN 110063990 A CN110063990 A CN 110063990A
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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 lymph cancer, 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 lymph cancer, 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 lymph cancer.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.
Lymthoma is initiated by the malignant tumour of lymphohematological, is mainly shown as Silent Neuritis enlargement of lymph nodes, liver and spleen
Enlargement, each histoorgan of whole body can be involved, and occur together the constitutional symptoms such as heat, night sweat, syntexis, itch.It is divided into according to oncocyte non-
Two class of Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL).Lymthoma has height heterogeneity, and therapeutic effect difference is very
Greatly, no matter from treatment intensity and prognosis all there is very big difference, but specific patient in different pathological types and lymthoma by stages
It should also be made a concrete analysis of according to patient's actual conditions.Because lymph is distributed in the body of animal body everywhere, various lifes are participated in
Reason reaction, therefore lymphocytic cancer cell be easier to transfer and it is difficult to treat.Thus develop effective, the lower antineoplastic of toxic side effect
Object 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).CBD shows the pharmacological activity such as anti-spasm, antianxiety, anti-inflammatory, anticancer, antidepression, insane
Shown in the treatment of a variety of diseases such as epilepsy, depression, parkinsonism, cancer huge application potential and industrial hemp at
For a kind of 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 performance of free radical antiangiogenic
The effect of cancer.
Industrial hemp floral leaf extract is united and applied in lymph cancer with artemisine compounds and explored by the present invention, with
Industrial hemp floral leaf extract and qinghaosu chlorins compound are widened in the clinical value of medicinal aspect.Inventor passes through pharmacodynamics
The study found that industrial hemp floral leaf extract joint artemisine compounds can effectively inhibit tumour growth, especially lymph cancer.
It can be seen that industrial hemp floral leaf extract and artemisinin derivatives, which are used in combination, is preparing antiangiogenic cancer field with fine
Application prospect.
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 lymph cancer drug.
The third aspect of the present invention provides a kind of method treated and/or prevent lymph cancer, and this method is will to treat effectively
The the first active constituent industrial hemp floral leaf extract and the second active constituent artemisinin derivatives of amount are administered in combination to needs
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 individual.
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 the pharmacodynamics of industrial hemp floral leaf extract Yu artemisine compounds combination therapy lymph cancer respectively
Experiment.The results show that industrial hemp floral leaf extract of the present invention and artemisine compounds use in conjunction are shown to lymph cancer
Therapeutic effect.
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 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 lymph cancer, operate as follows: weighing industrial hemp floral leaf
Extract 500mg, Artesunate 400mg, add water for injection 200mL, adjust pH value with 8% NaOH solution and make it dissolve；It is added
Sodium chloride 3g adds 0.2% active carbon to boil 15 minutes, and filtering, filtrate injects water to 1000mL；Medical fluid is with 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 lymph cancer, operate as follows: weighing industrial hemp floral leaf and mention
Object 50g, Artemether 40g, another taking polyethylene glycol 4000 and appropriate Macrogol 6000 are taken, is placed in heat in 80-85 DEG C of water-bath and melt
After melting, 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
Grain is 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 lymph cancer can effectively be treated by illustrating that industrial hemp floral leaf extract and artemisine compounds are used in combination.
The drug dose used in experimental example of the present invention is merely to illustrate technical effect of the invention, guarantor and is not intended to limit the present invention
Protect range.In experimental example, method therefor unless otherwise instructed, according to normal conditions, the item suggested of conventional method or manufacturer
Part carries out.Production firm person is not specified in agents useful for same together, is that can buy the conventional products obtained by market.
Experimental example 1: the effect of cannabidiol and qinghaosu use in conjunction to nude mouse endolymph growth of cancer cells
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: lymphocytic cancer cell VX2
3) male nude mouse, 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
VX2 tumor tissues suspension, the cell of logarithmic growth phase are cultivated, digestion is counted at 1.25 × 107/ ml concentration, with PBS weight
It is saved on ice after outstanding.Nude mice is taken, 100 μ l are inoculated with after VX2 cell suspension is mixed with Matrigel with 4:1 in nude mice by subcutaneous.It sees
Nude mice tumor formation situation is examined, and measures the longest diameter (L) and shortest diameter (S) of subcutaneous tumors, to gross tumor volume (V=L × S2/ 2) reach
100mm3Afterwards, start to treat according to grouping.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 lymph cancer has significant curative effect to lymph 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 nude mouse endolymph growth of cancer cells
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 lymph cancer can effectively be inhibited by showing CBD and Artesunate list medicine, have significant curative effect to lymph cancer, and two medicines join
Closing has more significant inhibitory effect using the growth to tumour.
Experimental example 3: the effect of cannabidiol and dihydroartemisinine use in conjunction to nude mouse endolymph growth of cancer cells
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 lymph cancer can effectively be inhibited by showing CBD and dihydroartemisinine list medicine, have significant curative effect, and two medicines to lymph cancer
The growth to tumour, which is used in combination, has more significant inhibitory effect.
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 rise in terms for the treatment of lymph cancer
Unexpected synergy is arrived.
Claims (11)
1. the drug combination of a kind of industrial hemp floral leaf extract and artemisine compounds is in the therapeutic agent of lymph cancer
Using.
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 lymph cancer 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 |
|---|---|---|---|
| CN201910506125.4A CN110063990A (en) | 2019-06-12 | 2019-06-12 | A kind of pharmaceutical composition and preparation method thereof for treating lymph cancer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910506125.4A CN110063990A (en) | 2019-06-12 | 2019-06-12 | A kind of pharmaceutical composition and preparation method thereof for treating lymph cancer |
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| Publication Number | Publication Date |
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| CN110063990A true CN110063990A (en) | 2019-07-30 |
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| CN201910506125.4A Pending CN110063990A (en) | 2019-06-12 | 2019-06-12 | A kind of pharmaceutical composition and preparation method thereof for treating lymph cancer |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| 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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| CB02 | Change of applicant information | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190730 |
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| WD01 | Invention patent application deemed withdrawn after publication |