CN110151824A - A kind of pharmaceutical composition and preparation method thereof for treating hypopharyngeal cancer - Google Patents

A kind of pharmaceutical composition and preparation method thereof for treating hypopharyngeal cancer Download PDF

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Publication number
CN110151824A
CN110151824A CN201910505673.5A CN201910505673A CN110151824A CN 110151824 A CN110151824 A CN 110151824A CN 201910505673 A CN201910505673 A CN 201910505673A CN 110151824 A CN110151824 A CN 110151824A
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CN
China
Prior art keywords
active constituent
preparation
leaf extract
industrial hemp
floral leaf
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Withdrawn
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CN201910505673.5A
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Chinese (zh)
Inventor
栾云鹏
郑双庆
李志朋
李襄
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Individual
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Individual
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Priority to CN201910505673.5A priority Critical patent/CN110151824A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365Lactones
    • A61K31/366Lactones having six-membered rings, e.g. delta-lactones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/60Moraceae (Mulberry family), e.g. breadfruit or fig
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

Abstract

The present invention provides one kind to the treatment effective combination medicine of hypopharyngeal 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 hypopharyngeal cancer, is had a good application prospect.Patent describes the pharmaceutical compositions and preparation method thereof, belong to pharmaceutical field.

Description

A kind of pharmaceutical composition and preparation method thereof for treating hypopharyngeal cancer
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 hypopharyngeal 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.
The disease incidence of hypopharyngeal cancer (hypopharyngeal cancer) accounts for 1.4% ~ 5.0%, Zhan Quan of head-neck malignant tumor The 0.3% of body malignant tumour is common head-neck malignant tumor, although clinically a variety of complex treatment hands of Preserving laryngeal function Section improves the quality of life of Hypopharyngeal Cancer Patients, but overall survival is not significantly improved.The therapeutic choice of hypopharyngeal cancer includes hand The methods of art, radiotherapy, chemotherapy.But the main symptom of Hypopharyngeal Cancer Patients is unobvious, early detection is not easy to, until swallowing The long tumor of difficult or neck, which is seen a doctor, determines hypopharyngeal cancer, after still having nearly half Hypopharyngeal Cancer Patients head to examine as advanced stage or due to operation at present Relapse and metastasis enters terminal illness state, no healing chance.Thus develop effective, the lower anti-tumor drug meaning of toxic side effect Great and clinical treatment the urgent need of justice.
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-hypopharynx The effect of cancer.
Industrial hemp floral leaf extract is united and applied in hypopharyngeal 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 hypopharyngeal cancer. It can be seen that industrial hemp floral leaf extract and artemisinin derivatives, which are used in combination, is preparing anti-hypopharyngeal 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 hypopharynx cancer drug.
The third aspect of the present invention provides a kind of method treated and/or prevent hypopharyngeal 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 hypopharyngeal 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 hypopharyngeal 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 hypopharyngeal 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 hypopharyngeal 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 hypopharyngeal 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 hypopharynx growth of cancer cells 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: people swallows squamous cell carcinoma strain Fadu
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
It cultivates people and swallows squamous cell carcinoma strain Fadu, the cell of logarithmic growth phase, digestion is counted at 8 × 107/ ml concentration, with PBS weight It is saved on ice after outstanding.Nude mice is taken, is inoculated with 100 μ l in nude mice by subcutaneous.Nude mice tumor formation situation is observed, and measures the longest diameter of subcutaneous tumors (L) and shortest diameter (S), to gross tumor volume (V=L × S2/ 2) reach 100mm3Afterwards, start to treat according to grouping.Measurement one in every 3 days Secondary nude mouse tumor volume, 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 hypopharyngeal cancer has significant curative effect to hypopharyngeal 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 hypopharynx growth of cancer cells 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 hypopharyngeal cancer can effectively be inhibited by showing CBD and Artesunate list medicine, have significant curative effect to hypopharyngeal 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 hypopharynx growth of cancer cells in nude mouse
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 hypopharyngeal cancer can effectively be inhibited by showing CBD and dihydroartemisinine list medicine, have significant curative effect, and two medicines to hypopharyngeal 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 hypopharyngeal 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 hypopharyngeal 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 hypopharyngeal 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.
CN201910505673.5A 2019-06-12 2019-06-12 A kind of pharmaceutical composition and preparation method thereof for treating hypopharyngeal cancer Withdrawn CN110151824A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910505673.5A CN110151824A (en) 2019-06-12 2019-06-12 A kind of pharmaceutical composition and preparation method thereof for treating hypopharyngeal cancer

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910505673.5A CN110151824A (en) 2019-06-12 2019-06-12 A kind of pharmaceutical composition and preparation method thereof for treating hypopharyngeal cancer

Publications (1)

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CN110151824A true CN110151824A (en) 2019-08-23

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Country Status (1)

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Application publication date: 20190823

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