CN110403924A - A kind of pharmaceutical composition and preparation method thereof for treating cutaneous melanoma - Google Patents
A kind of pharmaceutical composition and preparation method thereof for treating cutaneous melanoma Download PDFInfo
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- CN110403924A CN110403924A CN201910462531.5A CN201910462531A CN110403924A CN 110403924 A CN110403924 A CN 110403924A CN 201910462531 A CN201910462531 A CN 201910462531A CN 110403924 A CN110403924 A CN 110403924A
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- active constituent
- industrial hemp
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- class compound
- pharmaceutical composition
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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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The present invention provides one kind to the treatment effective combination medicine of cutaneous melanoma, the preparation being prepared containing the first active constituent industrial hemp class compound and the second active constituent artemisine compounds and the pharmaceutically acceptable auxiliary material of the two.Industrial hemp class compound and artemisine compounds use in conjunction can be used for preparing anti-tumor drug, and the pharmaceutical composition safe-dosaging limits are big, good effect, and the treatment for dermal melanin tumour has a good application prospect.Patent describes the compositions and preparation method thereof, belong to pharmaceutical field.
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 cutaneous melanoma therapeutic agent.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.
Malignant melanoma of skin (cutaneous malignant melanoma, CMM), is initiated by dermal melanin
The high malignancy tumour of cell because melanocyte originates from the neural crest of embryonic stage, therefore can betide skin, eyeball, disappear
Change the positions such as road, reproductive system, but most common with malignant melanoma of skin.Lymph easily occurs for melanoma early stage and blood road turns
It moves, poor prognosis treats it there is no unified and effective scheme at this stage.Currently, the therapeutic modality of CMM is still cut with early operation
It removes, based on the complex treatment of householder methods such as traditional Radiotherapy chemotherapy of postoperative combination.But still there is nearly half CMM patient first at present
It examines as advanced stage or terminal illness state, no healing chance is transferred into due to recurrence after operation.Thus develop effective, malicious pair
Act on that lower anti-tumor drug is significant and the urgent need of clinical treatment.
CBD also shows the pharmacological activity such as anti-spasm, antianxiety, anti-inflammatory, anticancer, antidepression, in epilepsy, depression, pa gold
Huge application potential and Industry hemp are shown in the treatment of a variety of diseases such as gloomy disease, cancer becomes a kind of heavy
The bio-pharmaceuticals raw material wanted.
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.These
Artemisinin derivative not only has efficient antimalarial, and low toxicity works the advantages that rapid, also in antitumor, immunosupress such as erythema wolf
Sore, anti parasitic are anti-inflammatory etc. to achieve compared with good therapeutic effect.Especially in anti-tumor aspect, artemisine compounds
The main generation by inducing cell apoptosis, inhibiting free radical inhibits the effects of angiogenesis 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 mouse skin melanoma that industrial hemp class compound joint artemisine compounds can effectively inhibit carcinogen to induce
It generates and grows.It can be seen that industrial hemp class compound and artemisinin derivative, which are used in combination, is preparing anti-tumor drug neck
Domain has a good application prospect, and can be used for treating cutaneous melanoma.
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 cutaneous melanoma.
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 be 99:1~
1:99, preferably 20:1~1:99, between further preferably 20:1~1:20, preferred first active constituent and the second activity
The molar ratio of ingredient is between 5:1~1:5.
Combination medicine of the present invention, the pharmaceutical dosage form are oral preparation or ejection preparation；Preferably, the mouth
Formulation is selected from one of tablet, capsule, soft capsule, granule, suspension, dripping pill, pill, oral liquid；
Preferably, the tablet is conventional tablet, dispersible tablet, oral disnitegration tablet or sustained release tablets；Preferably, the ejection preparation is injection
Liquid or powder-injection.
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.
Combination medicine of the present invention, wherein industrial hemp class compound and artemisine compounds separately from each other,
Serially or simultaneously it is administered.
The present invention has carried out industrial hemp class compound respectively and has combined inhibition cutaneous melanoma with artemisine compounds
The experiment in vivo of growth.The results show that industrial hemp class compound of the present invention is shown with artemisine compounds use in conjunction
To 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 cutaneous melanoma, operate as follows: weighing industrial work
Sparetime university fried dough twist leaf extract 500mg, Artesunate 500mg, add water for injection 200mL, and adjusting pH value with 8% NaOH solution makes
It is dissolved；Sodium chloride 3g is added, 0.2% active carbon is added to boil 15 minutes, filters, filtrate injects water to 1000mL；Medical fluid
Filtered with 0.22 μm of miillpore filter, filling 5 bottles, roll lid, in 110 DEG C of pressure sterilizings 40 minutes to get.
Embodiment 2
The present embodiment provides a kind of dripping pills of pharmaceutical composition for treating cutaneous melanoma, operate as follows: weighing Industry
Cannabis leaf extract 50g, arteether 10g, another taking polyethylene glycol 4000 and appropriate Macrogol 6000, are placed in 80-85 DEG C of water
In bath after heating melting, weighed above two raw material is added, mixes, is kept for 75 DEG C of temperature, instills atoleine (0-5 DEG C)
In, 1000 are made to get drops of the invention.
To better illustrate objects and advantages of the present invention, the present invention is by following experiments example to the present invention as antitumor
The effect of agent is described, and illustrating that industrial hemp class compound is used in combination with artemisine compounds can effectively inhibit skin black
Melanoma tumour growth.The drug dose used in experimental example of the present invention is merely to illustrate technical effect of the invention, Er Feiyong
In limiting the scope of the invention.In experimental example, method therefor unless otherwise instructed, according to normal conditions, conventional method
Or the condition that manufacturer suggests carries out.Production firm person is not specified in agents useful for same together, is that can buy to obtain by market
The conventional products obtained.
Experimental example 1: the effect of cannabidiol and qinghaosu use in conjunction to nude mouse inner skin melanoma cell growth
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 DEG C of preservations；Qinghaosu (ART) and its derivative dihydroartemisinine (DHA), Artesunate (ARS) are purchased from purchased from Mike
Woods biochemical technology Co., Ltd, Chinese Shanghai are (public purchased from Sigma-Aldrich with 4 DEG C of 1% methylcellulose refrigerated respectively
Department, Chinese Shanghai) solution dissolution be configured to corresponding solution, it is ready-to-use.
2) cell: B16 melanoma cells
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 50mg/kg, intraperitoneal injection, once a day
3) ART treatment group: ART 50mg/kg, stomach-filling, once a day
4) CBD+ART treatment group: CBD 30mg/kg, intraperitoneal injection, while ART 20mg/kg, stomach-filling, once a day
3. nude mice by subcutaneous Tumorigenesis
B16 melanoma cells, the cell of logarithmic growth phase are cultivated, digestion is counted at 1.6 × 106/ ml concentration, with PBS weight
It is saved on ice after outstanding.Take nude mice, in left side 0.2 ml of dorsal sc injection B16 melanoma cells suspension/only, altogether be inoculated with
30, tumour occurs within about 2 weeks.Nude mice tumor formation situation is observed, 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, 4 weeks
After put to death animal.
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 cutaneous melanoma has significant curative effect to cutaneous melanoma, and two medicines are used in combination pair
The growth of tumour has more significant inhibitory effect.
Experimental example 2: the work of cannabidiol and Artesunate use in conjunction to nude mouse inner skin melanoma cell growth
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 cutaneous melanoma can effectively be inhibited by showing CBD and Artesunate list medicine, be had to cutaneous melanoma 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 nude mouse inner skin melanoma cell growth
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 cutaneous melanoma can effectively be inhibited by showing CBD and dihydroartemisinine list medicine, be had to cutaneous melanoma significant
Curative effect, and the growth to tumour is used in combination with more significant inhibitory effect in two medicines.
With dosage industrial hemp diphenol+artemisinin-based drug processing group result better than industrial hemp diphenol drug-treated group,
Artemisinin-based drug processing group, it was demonstrated that industrial hemp diphenol and the combination of qinghaosu medicine series are in terms for the treatment of cutaneous melanoma
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 cutaneous melanoma therapeutic agent.
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 the second active constituent artemisine compounds and optional pharmaceutically acceptable carrier or tax
Shape agent.
3. combination medicine as claimed in claim 2 includes at least wherein the first active constituent is industrial hemp class compound
50% or more industrial hemp diphenol (CBD) or derivatives thereof.
4. pharmaceutical composition as claimed in claim 2, wherein the second active constituent is artemisine compounds, it is a effective amount of
One of qinghaosu, dihydroartemisinine, Artesunate, Artemether, arteether or its officinal salt, hydrate are several
Mixture.
5. the pharmaceutical composition as described in claim 2-4, wherein the molar ratio of the first active constituent and the second active constituent is
99:1~1:99.
6. the pharmaceutical composition as described in claim 2-4, wherein the molar ratio of the first active constituent and the second active constituent is
20:1~1:99.
7. such as the combination medicine of any one of claim 2-4, 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 to be applied to treatment of cancer, especially cutaneous melanoma
Treatment.
9. the combination medicine as described in claim 1-4, which is characterized in that the pharmaceutical dosage form is oral preparation or injection system
Agent；Preferably, the oral preparation is selected from tablet, capsule, soft capsule, granule, suspension, dripping pill, pill, oral solution
One of body preparation；Preferably, the tablet is conventional tablet, dispersible tablet, oral disnitegration tablet or sustained release tablets；Preferably, institute
Stating ejection preparation is injection or powder-injection.
10. the combination medicine as described in claim 1-4, wherein the first active constituent 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 |
|---|---|---|---|
| CN201910462531.5A CN110403924A (en) | 2019-05-30 | 2019-05-30 | A kind of pharmaceutical composition and preparation method thereof for treating cutaneous melanoma |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910462531.5A CN110403924A (en) | 2019-05-30 | 2019-05-30 | A kind of pharmaceutical composition and preparation method thereof for treating cutaneous melanoma |
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| Publication Number | Publication Date |
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| CN110403924A true CN110403924A (en) | 2019-11-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201910462531.5A Withdrawn CN110403924A (en) | 2019-05-30 | 2019-05-30 | A kind of pharmaceutical composition and preparation method thereof for treating cutaneous melanoma |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112137935A (en) * | 2020-10-26 | 2020-12-29 | 苏州唐基生物科技有限公司 | Composition and application thereof |
-
2019
- 2019-05-30 CN CN201910462531.5A patent/CN110403924A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112137935A (en) * | 2020-10-26 | 2020-12-29 | 苏州唐基生物科技有限公司 | Composition and application thereof |
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| Date | Code | Title | Description |
|---|---|---|---|
| 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 |
|
| CB02 | Change of applicant information | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20191105 |
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| WW01 | Invention patent application withdrawn after publication |