CN100502867C - Preparation of sinomenine as antineoplastic medicament - Google Patents
Preparation of sinomenine as antineoplastic medicament Download PDFInfo
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- CN100502867C CN100502867C CNB2005101346046A CN200510134604A CN100502867C CN 100502867 C CN100502867 C CN 100502867C CN B2005101346046 A CNB2005101346046 A CN B2005101346046A CN 200510134604 A CN200510134604 A CN 200510134604A CN 100502867 C CN100502867 C CN 100502867C
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Abstract
An antineoplastic action of coculine and the composite medicine containing said coculine and the application of coculine in preparing antineoplastic medicines are disclosed.
Description
Technical field
The present invention relates to a kind of antitumor medicine composition and its production and use that is used for.More specifically, the antitumor action that the present invention relates to sinomenine and contain the compound medicament composition of sinomenine, and the purposes in the preparation antitumor drug.
Background technology
Tumor is a kind of disease of serious threat people's health, and in order to treat tumor effectively, people are seeking various materials with tumor suppression or killing action.
Sinomenine (Sinomenime) is the alkaloid that extracts from Chinese medicine Caulis Sinomenii (Sinomenium acutum Rehd.et.wils.).Its chemistry 7,8-two dehydrogenation-4-hydroxyl-3.7-dimethyl hydrogen-based-17-methyl-9a, 13a by name, 14a-morphinan-6-ketone, its molecular formula is C
19H
23NO
4, molecular weight is 329.38.Sinomenine has pharmacological actions such as antiinflammatory, analgesia, blood pressure lowering, arrhythmia, and its preparation has been used for the treatment of rheumatoid arthritis clinically.
Yet, do not report the antineoplastic action of sinomenine up to now, more not with sinomenine as the main antitumor drug of effective ingredient.
In sum, in order to treat tumor, this area presses for the medicine that medicine, the especially active component of developing new inhibition tumor derive from Chinese crude drug.
Summary of the invention
Purpose of the present invention just provides a kind of anti-tumor active ingredient-sinomenine that derives from Chinese medicine.
Another object of the present invention provides the medicine and/or the dietary supplement of the pure Chinese medicine extract that contains sinomenine.
In a first aspect of the present invention, a kind of purposes of sinomenine is provided, it is used to prepare the pharmaceutical composition that suppresses tumor.
In another preference, by the gross weight of compositions, described pharmaceutical composition contains following active component:
Sinomenine 30-75mg/g;
Paeoniflorin 8-15mg/g;
Ferulic acid 1.5-3mg/g;
And pharmaceutically acceptable carrier.
In another preference, the content of sinomenine is 40-60mg/g in the described compositions, and paeoniflorin is 10-15mg/g.
In another preference, the content of sinomenine is 20mg/ agent or 30mg/ agent in the described compositions.
In another preference, described pharmaceutical composition contains the necessary component that is selected from down group:
The Caulis Sinomenii of 45-85 parts by weight;
The Radix Paeoniae Alba of 8-20 parts by weight;
The Radix Angelicae Sinensis of 3-10 parts by weight;
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, and the pharmaceutically acceptable carrier of surplus.
In another preference, described pharmaceutical composition contains:
The Caulis Sinomenii of 55-85 parts by weight;
The Radix Paeoniae Alba of 10-20 parts by weight;
The Radix Angelicae Sinensis of 4-10 parts by weight;
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 50-99% of composition total weight.
In another preference, described pharmaceutical composition contains:
The Caulis Sinomenii of 60-85 parts by weight;
The Radix Paeoniae Alba of 12-15 parts by weight;
The Radix Angelicae Sinensis of 5-8 parts by weight.
In another preference, described tumor is selected from down group: pulmonary carcinoma, hepatocarcinoma, mastocarcinoma or carcinoma of prostate.
In another preference, described pharmaceutical composition is tablet or capsule preparations.
In another preference, described pharmaceutical composition also contains the material that is selected from down group: cisplatin, paclitaxel, TNF-α, IFN-γ, angiostatin (Angiostatin), endostatin (Endostatin), etoposide, amycin, 5-fluorouracil, NSC-241240 or ifosfamide.
In a second aspect of the present invention, a kind of purposes of mixture is provided, described mixture is by the Caulis Sinomenii of 45-85 parts by weight; The Radix Paeoniae Alba of 8-20 parts by weight; Constitute with the Radix Angelicae Sinensis of 3-10 parts by weight, perhaps described mixture contains sinomenine 30-75mg/g; Paeoniflorin 8-15mg/g; With ferulic acid 1.5-3mg/g, wherein, described mixture is used to prepare the medicine that suppresses tumor.
In a third aspect of the present invention, a kind of purposes of sinomenine is provided, be used to prepare the compositions that suppresses nuclear factor NF-kB activity.
In a fourth aspect of the present invention, the method for preparing pharmaceutical composition of the present invention or dietary supplement is provided, it comprises step:
(1). choose the higher Caulis Sinomenii coarse powder of sinomenine content and in the percolation narrow-necked earthen jar, extract the aqueous solution that obtains containing sinomenine to soak into the back at 0.1-0.5% sulphuric acid liquid, transfer pH=12 ± 0.5 with lime cream then, must precipitate, again with the 90-95% alcohol reflux, concentrating under reduced pressure gets the sinomenine coarse powder then.Add hydrochloric acid again and get sinomenine hydrochloride in coarse powder, recrystallization is dissolved in this crystallization ebullient 60-70% (as 65%) ethanol at last and adds ammonia and transfers pH to 9 ± 0.2 then, can obtain purity and be the sinomenine greater than 95% (as 98%).
(2). obtain Radix Angelicae Sinensis and Radix Paeoniae Alba extractum with alcohol extracting method;
(3). Caulis Sinomenii extractum is fitted over Radix Angelicae Sinensis and Radix Paeoniae Alba extractum, and acquisition has the pharmaceutical composition of the active constituent of above-mentioned concentration,
Wherein the order of step (1) and (2) is interchangeable.
Preferably, used Caulis Sinomenii medical material is the higher Caulis Sinomenii coarse powder of sinomenine content.
The specific embodiment
The inventor is surprised to find that through extensive and deep research the active component sinomenine of Caulis Sinomenii has the effect of good inhibition tumor growth.No matter be to use sinomenine separately, the compositions that also is to use the Caulis Sinomenii and the Radix Paeoniae Alba and Radix Angelicae Sinensis three to form by a certain percentage all can obtain the good antitumor effect.Particularly, sinomenine 60% suppression ratio can occur to the Mice Bearing Lewis Lung Cancer model, and dose-effect relationship is obvious.The experiment prompting, this effect is relevant with sinomenine inhibition nuclear factor NF-kB activity.Finished the present invention on this basis.
Anti-tumor compositions of the present invention, be a kind of be that necessary component or corresponding effective ingredient (being sinomenine) they are the compositions of neccessary composition with Caulis Sinomenii.Compositions of the present invention can be pharmaceutical composition or dietary supplement.
A kind of preferred pharmaceutical composition is the compound medicament composition that contains sinomenine, especially contains the medicine of the pure Chinese medicine extract of sinomenine.
A kind of preferred compound be with Caulis Sinomenii be necessary component or corresponding effective ingredient (being sinomenine) be neccessary composition simultaneously with the Radix Paeoniae Alba and when be classified as complementary necessary component or accordingly effective ingredient (being white peony root's total glycoside and ferulic acid) be the compositions of complementary neccessary composition.Compositions of the present invention can be pharmaceutical composition or dietary supplement.A kind of preferred compositions is disclosed in and is entitled as among the Chinese patent ZL01819981.X of " be used for the treatment of or improve arthritic pharmaceutical composition and dietary supplement ", and the document all is incorporated herein by reference.
As used herein, term " necessary component " refers to necessary Chinese medicine medical material, i.e. Caulis Sinomenii (Sinomemiumacutum).
As used herein, term " complementary necessary component " refers to complementary necessary Chinese medicine medical material, i.e. the Radix Paeoniae Alba (Paeomia lactiflora) and Radix Angelicae Sinensis (Angelica sinensis).
As used herein, term " neccessary composition " refers to the chemical substance as necessity of active component, i.e. sinomenine (Sinomemine).In the present invention, except using sinomenine, can also use the salt of sinomenine, for example pharmaceutically acceptable salt hydrochlorate, sulfate, acetate, mesylate etc.
As used herein, term " complementary neccessary composition " refers to the complementary necessary chemical substance as active component, promptly white peony root's total glycoside (total glucosides of paecony, TGP) and ferulic acid (Ferolic acid).
As used herein, term " white peony root's total glycoside " and " paeoniflorin " are used interchangeably, and all refer to the portugal glycoside material in the Radix Paeoniae Alba.
As used herein, term " comprise " comprised " containing ", " basically by ... constitute " and " by ... formation ".
As used herein, term " basically by ... constitute " refer in compositions, except containing neccessary composition or necessary component, also can contain a spot of and not influence the submember and/or the impurity of effective ingredient.For example, can contain sweeting agent to improve taste, antioxidant in case oxidation, and other this areas additive commonly used.Usually Caulis Sinomenii (Sinomemium acutum), the Radix Paeoniae Alba (Paeomia lactiflora) and Radix Angelicae Sinensis (Angelica sinensis) account at least 70% of whole Chinese medicine medical material weight, and preferably at least 80%, more preferably at least 90%.
As used herein, term " pharmaceutically acceptable carrier " refers to be used for the treatment of the carrier of agent administration, comprises various excipient and diluent.This term refers to some medicament carriers like this: they itself are not necessary active component, and do not have undue toxicity after using.Suitable carriers is well known to those of ordinary skill in the art.(Mack Pub.Co. can find discussing fully about pharmaceutically acceptable excipient in N.J.1991) at Remington ' s Pharmaceutical Sciences.Acceptable carrier can contain liquid on combination of Chinese medicine is learned, as water, saline, glycerol and ethanol.In addition, also may there be complementary material in these carriers, as wetting agent or emulsifying agent, pH buffer substance etc.Come from Caulis Sinomenii, the Radix Paeoniae Alba, Radix Angelicae Sinensis remove neccessary composition (be sinomenine (Sinomemine), white peony root's total glycoside (Total glucosides of paecony, TGP) and ferulic acid (Ferolic acid).) outside inessential composition, and other inessential compositions (for example other complementary medical materials) are also included within the definition of pharmaceutically acceptable carrier.
As used herein, term " compositions of the present invention " comprises pharmaceutical composition and dietary supplement, as long as they contain or basically by (1) Caulis Sinomenii or sinomenine; (2) Radix Paeoniae Alba or white peony root's total glycoside; (3) Radix Angelicae Sinensis or ferulic acid constitute.Usually, the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, preferably 50-99%, more preferably 60-90%.
In addition, the present composition can contain other materials for the treatment of tumor, for example cisplatin, paclitaxel, TNF-α, IFN-γ, Angiostatin, Endostatin, etoposide, amycin, 5-fluorouracil, NSC-241240, ifosfamide or its combination.
In compound medicament composition of the present invention, be (1) Caulis Sinomenii (Sinomemium acutum) as three kinds of Chinese medicine medical materials of necessary component, active component wherein is sinomenine (Sinomemine); (2) Radix Paeoniae Alba (Paeomia lactiflora); Active component wherein be white peony root's total glycoside (Total glucosides of paecony, TGP); (3) Radix Angelicae Sinensis (Angelica sinensis), active component wherein are ferulic acid (Ferolic acid).
Medicine of the present invention is closely related to the content of the inhibition effect of tumor and necessary active component.Studies show that, in order to obtain stable inhibition tumor effect, should make that the sinomenine component content reaches certain scope in this medicine, 20mg/ agent according to appointment, 30mg/ agent or 40mg/ agent.
In addition, in preferred compound medicine, the scope of the reasonable content of each composition is:
Sinomenine 30-75mg/g, 40-60mg/g preferably,
Paeoniflorin 8-15mg/g, preferably, 10-15mg/g,
Ferulic acid 1.5-3mg/g.
Except limiting the compositions of the present invention by necessary active component, the proportioning of also available necessary component (medical material) limits compound medicament composition of the present invention.
In the present composition, by weight, the appropriate proportioning of three kinds of necessary medical materials is:
45-85 parts by weight, preferably 55-85 parts by weight, the more preferably Caulis Sinomenii of 60-85 parts by weight;
8-20 parts by weight, preferably 10-20 parts by weight, the more preferably Radix Paeoniae Alba of 12-15 parts by weight;
The 3-10 parts by weight, 4-10 parts by weight preferably, the Radix Angelicae Sinensis of 5-8 parts by weight more preferably,
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, preferably 50-99%, more preferably 60-95%.The material of surplus is pharmaceutically acceptable carrier, for example starch, maltodextrin etc.
In order to make preparation that good therapeutic effect be arranged, the effective active component content in the preparation is crucial.The inventor has also set up a cover and has detected in the said preparation high performance liquid chromatogram (HPLC) assay method of active component in each Chinese crude drug for this reason, monitors the various active component in raw material and the preparation.
Pharmaceutical composition of the present invention or dietary supplement can be made the dosage form of any routine by conventional method, preferably tablet, capsule preparations, granule, pill, oral liquid, injection etc.
In another aspect of this invention, provide a kind of method for preparing pharmaceutical composition of the present invention or dietary supplement.
Conventional Chinese medicine extraction method is difficult to make the active component in the extract to reach the curative effect that higher concentration guarantees said preparation.The inventor finds that when suppressing tumor according to pharmacological research with Caulis Sinomenii, adult's effective dose is preferably 40-80mg/ days, should contain sinomenine 40-60mg in every like this restraint agent, and this concentration is that general extracting method is unapproachable.A kind of effective ways that extract sinomenine have been tested for this reason.
In this extraction method, at first choose the higher Caulis Sinomenii coarse powder of sinomenine content and in the percolation narrow-necked earthen jar, extract the aqueous solution that obtains containing sinomenine to soak into the back at 0.1-0.5% sulphuric acid liquid, transfer pH=12 ± 0.5 with lime cream then, must precipitate, again with the 90-95% alcohol reflux, concentrating under reduced pressure gets the sinomenine coarse powder then.Add hydrochloric acid again and get sinomenine hydrochloride in coarse powder, recrystallization is dissolved in this crystallization ebullient 60-70% (as 65%) ethanol at last and adds ammonia and transfers pH to 9 ± 0.2 then, can obtain purity and be the sinomenine greater than 95% (as 98%).
Use conventional alcohol extracting method simultaneously, obtain the extractum of the Radix Angelicae Sinensis and the Radix Paeoniae Alba.For example, Radix Angelicae Sinensis is refluxed with 70% ethanol water, then the solution that obtains is concentrated, thereby obtain Radix Angelicae Sinensis concentrate (as extractum).In addition, through spray do after, also can obtain Radix Angelicae Sinensis concentrate powder.Similarly, can obtain the extractum of the Radix Paeoniae Alba.Certainly, preferably, can obtain to contain simultaneously the concentrate (as extractum) of Radix Angelicae Sinensis and two kinds of active princlples of the Radix Paeoniae Alba.
At last,, more a certain proportion of these extractum are fitted over together, so just can reach the concentration that needs according to the needs of preparation.
In a preference, the method for preparing compound medicine of the present invention comprises step:
(1), makes purity for greater than 95% sinomenine with above-mentioned method for optimizing.
(2), obtain Radix Angelicae Sinensis and Radix Paeoniae Alba extractum with conventional alcohol extracting method.
(3), according to the preparation needs, again these two kinds of extractum and sinomenine are fitted over together, so just can reach the concentration that needs, wherein the order of step (1) and (2) is interchangeable.
The invention has the advantages that:
(1) component is simple, active component is clear and definite and with strong points;
(2) can quantitatively control active component, thereby ensure the quality of products;
(3) with low cost;
(4) inhibitory action to tumor is obvious.
Further set forth the present invention below in conjunction with embodiment.Should be understood that these embodiment only to be used to set forth the present invention and be not used in restriction the present invention.In an embodiment, percentage ratio is weight percentage, and umber is parts by weight, unless stated otherwise.
Embodiment 1
The preparation of pharmaceutical composition A
In this embodiment, provide a kind of pharmaceutical composition (compositions A), wherein, the proportioning of three kinds of Chinese medicines is:
Caulis Sinomenii 82 parts by weight (820 gram)
The Radix Paeoniae Alba 12 parts by weight (120 gram)
Radix Angelicae Sinensis 6 parts by weight (60 gram)
All through the HPLC test, quality meets the requirements three kinds of used in the present embodiment Chinese medicines.
At first choose the higher Caulis Sinomenii coarse powder of sinomenine content and in the percolation narrow-necked earthen jar, extract the aqueous solution that obtains containing sinomenine to soak into the back at 0.4% sulphuric acid liquid, transfer pH=12 with lime cream then, must precipitate, again with 95% alcohol reflux, concentrating under reduced pressure gets the sinomenine coarse powder then.Add hydrochloric acid again and get sinomenine hydrochloride in coarse powder, recrystallization then is dissolved in this crystallization ebullient 65% ethanol at last and adds ammonia and transfers pH to 9, can obtain purity and be 98% sinomenine.
Take by weighing the Radix Angelicae Sinensis or the Radix Paeoniae Alba, add 70% alcohol reflux, the extracting solution concentrating under reduced pressure becomes the extractum shape, and 1 gram eumenol is equivalent to 1.6 gram crude drugs, and 1 gram Radix Paeoniae Alba extractum is equivalent to 4.4 gram crude drugs.
With sinomenine and Radix Angelicae Sinensis, the abundant mixing of Radix Paeoniae Alba alcohol-extracted extract, carried out vacuum drying (60～70 ℃) 3.5-4.0 hour, make dry extract, dry extract to be pulverized, 60 orders sieve, and incapsulate.In this embodiment, Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for about 80% of composition total weight.
Embodiment 2
The preparation of pharmaceutical composition B
Press the extracting method described in the embodiment 1, make sinomenine respectively, the Radix Paeoniae Alba and Radix Angelicae Sinensis are made concentrated extract.Each extract is behind assay, and according to the form below A prescription takes by weighing the back fully to be mixed with adjuvant (microcrystalline cellulose and magnesium stearate), and with encapsulating capsule behind the dry granulation, makes totally 1000 of capsule preparations, and the inclusions of every capsules is 300mg or 250mg.
Table A: every capsules contains various one-tenth dosis refractas
| Content (by crude drug) | Content (by active component) | |
| Caulis Sinomenii or sinomenine | 2g Caulis Sinomenii (80 weight portion) | 60mg sinomenine/g compositions |
| The Radix Paeoniae Alba or peonine | The 350mg Radix Paeoniae Alba (14 weight portion) | 11mg peoniflorin/g compositions |
| Radix Angelicae Sinensis or ferulic acid | 75mg Radix Angelicae Sinensis (3 weight portion) | 1.5mg ferulic acid/g compositions |
Embodiment 3
The sinomenine hydrochlorate is converted into sinomenine
The sinomenine of the industrial production of China is the hydrochlorate of sinomenine at present, but in the world, monomer whose is more acceptant.Therefore in the present embodiment, the sinomenine hydrochlorate is converted into sinomenine.Method is as follows:
The sinomenine hydrochlorate of getting purchase is dissolved in 65% boiling ethanol, adds ammonia and transfers PH to 9-10, places and filters, and filtrate is at 40 ℃ of vacuum dryings, and gained white crystals powder is the sinomenine monomer.
Measure through HPLC, sinomenine content is more than 98%.
Because infrared spectrum has altitude feature, therefore can be used for the discriminating of medicine and determining of chemical constitution.Pass upright leaf transformation infrared spectrophotometer with Bruker VECTORZZ and measure the as above monomeric infrared spectrum of sinomenine of preparation, and with sinomenine standard substance available from the national drug biological product determination (lot number: 0774-200105) compare, both are identical as a result.
Embodiment 4
Sinomenine and compound recipe thereof are to the inhibitory action of tumor
Get the sinomenine compound capsule or the sinomenine monomer (purity 98%) of preparation in embodiment 2 and 3, test its inhibitory action tumor.
Test method is as follows:
Animal: conventional C57BL/6 mice, body weight 18-20 gram/only, 10 of every treated animals
Tumor source: Mice Bearing Lewis Lung Cancer
Dosage is provided with: sinomenine 140,70,35mg/kg, gastric infusion
Sinomenine compound recipe 800,400,200mg/kg, gastric infusion
Test procedure: Mice Bearing Lewis toes subcutaneous vaccination model: get the Lewis lung cancer of eugonic routine under the aseptic condition, prepare into about 2 * 10 with homogenate
7/ ml cell suspension is in the right toes subcutaneous vaccination 0.05ml/ Mus (about 1 * 10 of C57BL/6 mice
6Individual tumor cell), presses the administration of experimental design scheme next day, primary tumor tumour inhibiting rate successive administration 10 days, and with the caliper body outer long a of detection of dynamic lotus tumor toe, wide b, thick c diameter, so that π/6 * (a * b * c) formula calculates each lotus tumor toe volume, gets average and standard deviation, makes curve chart.The ten days lotus of operation intercepting later on tumor toes, lotus tumor toes are weighed, and calculate the suppression ratio of inoculation primary tumo(u)r by following formula:
The average lotus tumor of tumor control rate %=[(matched group average lotus tumor toes weight-administration group toes are heavy)/the average lotus tumor toes of the average lotus tumor of matched group toes weight-blank are heavy] * 100%
The result:
Sinomenine 140,70,35mg/kg, the treatment of the scheme of ig * 10 is respectively 57.08%, 46.22%, 32.19% to the curative effect of the Mice Bearing Lewis Lung Cancer of toes subcutaneous vaccination.
Sinomenine compound recipe 800,400,200mg/kg, the treatment of the scheme of ig * 10 is respectively 59.97%, 52.13%, 38.24% to the curative effect of the Mice Bearing Lewis Lung Cancer of toes subcutaneous vaccination, sees table 1 for details.
Table 1. sinomenine and sinomenine compound recipe are to Mice Bearing Lewis Lung Cancer (toes subcutaneous vaccination) primary tumor clinical trial result
Compare * * * P＜0.01 with negative control group, CTX is a cyclophosphamide, the on average heavy 0.10g of blank toes.
In addition, suppress the tumor test and show that compound recipe is better than folk prescription result (seeing Table 1).Therefore, can add in compound recipe has reinforcement and synergistic medical material, the especially Radix Paeoniae Alba and Radix Angelicae Sinensis (or its active component or its extract) to Caulis Sinomenii, thereby forms compound medicine.
Embodiment 5
The preparation of sinomenine folk prescription medicine
Get among the embodiment 3 sinomenine of preparation, and add appropriate amount of auxiliary materials, behind the dry granulation and incapsulate as oral agents or make tablet.Below be the content of sinomenine and adjuvant in every capsules.
Sinomenine 40mg
Adjuvant 260mg
Adjuvant is microcrystalline Cellulose, magnesium stearate.
Embodiment 6
The relation of necessary component or active component content and therapeutic effect
In this embodiment, tested the content of each medical material in the compound medicament composition of the present invention or its active component and suppress relation between the effect of effect aspect.
By being similar to embodiment 1 described method, be prepared as follows the compositions of proportioning, wherein the content of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis total amount and excipient is the percentage ratio that accounts for composition total weight.And test its inhibitory action in Mice Bearing Lewis toes subcutaneous vaccination model to tumor by embodiment 4 described methods.
| Composition no | Caulis Sinomenii (parts by weight) | The Radix Paeoniae Alba (parts by weight) | Radix Angelicae Sinensis (parts by weight) | Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis total amount (wt%) | Excipient (wt%) |
| 1 | 50 | 15 | 7 | 50 | 50% starch |
| 2 | 60 | 12 | 6 | 60 | 20% starch+maltodextrin |
| 3 | 70 | 10 | 5 | 70 | 30% maltodextrin |
| 4 | 80 | 20 | 10 | 80 | 20% starch |
The result shows that compared with the control, these compositionss all can have function of tumor inhibition, and suppression ratio is proportional with the consumption of sinomenine basically.
Compositions A among compositions 1-4 and the embodiment 1 and the compositions B among the embodiment 2 measure through high performance liquid chromatogram (HPLC), and the content of sinomenine is 30-75mg/g; Content of paeoniflorin is 8-15mg/g; Ferulaic acid content is 1.5-3mg/g.
Embodiment 7
The preparation of dietary supplement
By the method that is similar to embodiment 1, the preparation dietary supplement, wherein, the proportioning of three kinds of Chinese medicines is:
Caulis Sinomenii 60 parts by weight (600 gram)
The Radix Paeoniae Alba 10 parts by weight (100 gram)
Radix Angelicae Sinensis 5 parts by weight (50 gram)
The dry extract that makes is pulverized, and 60 orders sieve, and incapsulate.In this embodiment, Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for about 70% of composition total weight.
Embodiment 8
Sinomenine is to the inhibitory action of nuclear factor NF-kB activity
Nuclear factor NF-κ B plays critical effect in the anti-apoptosis mechanism of tumor, will cause the apoptosis of tumor cell so suppress the activity of tumor cell NF-κ B, thereby suppress growth of tumor.
Tested the influence of sinomenine with conventional method in the present embodiment to BALB/C mice peritoneal macrophage NF-kB activation, specific as follows: with sinomenine (20 μ mol/L) and control sample (not containing sinomenine) handle Turnover of Mouse Peritoneal Macrophages, after 2 hours under laser confocal microscope the NF-KB level of activity of observation of cell (representing) by measuring fluorescence intensity.
Found that (with the fluorescence intensity ratio value representation, its value is 2.01 to the activity of NF-κ B, is starkly lower than contrast (fluorescence intensity ratio is 5.20) after handling with sinomenine
The The above results prompting, sinomenine has inhibitory action to nuclear factor NF-kB activity, can promote apoptosis of tumor cells, thereby suppresses the growth of tumor cell.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (2)
1. the purposes of a sinomenine is characterized in that, is used to prepare the pharmaceutical composition that suppresses tumor, and wherein said tumor is a pulmonary carcinoma,
And by the gross weight of compositions, described pharmaceutical composition contains following active component:
Sinomenine 30-75mg/g;
Paeoniflorin 8-15mg/g;
Ferulic acid 1.5-3mg/g;
And pharmaceutically acceptable carrier;
Perhaps, described pharmaceutical composition contains the necessary component that is selected from down group:
The Caulis Sinomenii of 45-85 parts by weight;
The Radix Paeoniae Alba of 8-20 parts by weight;
The Radix Angelicae Sinensis of 3-10 parts by weight;
And the weight of Caulis Sinomenii+Radix Paeoniae Alba+Radix Angelicae Sinensis accounts for the 30-99% of composition total weight, and the pharmaceutically acceptable carrier of surplus.
2. the purposes of a mixture, described mixture is by the Caulis Sinomenii of 45-85 parts by weight; The Radix Paeoniae Alba of 8-20 parts by weight; Constitute with the Radix Angelicae Sinensis of 3-10 parts by weight, perhaps described mixture contains sinomenine 30-75mg/g; Paeoniflorin 8-15mg/g; With ferulic acid 1.5-3mg/g, it is characterized in that described mixture is used for preparation and suppresses lung cancer drugs.
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| US8829020B2 (en) | 2009-07-16 | 2014-09-09 | Mallinckrodt Llc | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
| CN108653287B (en) * | 2018-05-03 | 2020-06-05 | 北京市心肺血管疾病研究所 | Application of sinomenine in preventing and treating thoracic aortic dissection/aortic aneurysm |
| CN111773221B (en) * | 2020-07-21 | 2021-08-03 | 李蕴麟 | Application of sinomenine and derivatives or pharmaceutically acceptable salts thereof in preparing medicine for treating breast diseases |
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| 芍药甙对人肝癌细胞株Bel-7402增殖的影响. 晏雪生等.中西医结合肝病杂志，第11卷第5期. 2001 |
| 芍药甙对人肝癌细胞株Bel-7402增殖的影响. 晏雪生等.中西医结合肝病杂志，第11卷第5期. 2001 * |
| 阿魏酸的功能和应用. 欧仕益.广州食品工业科技，第18卷第4期. 2002 |
| 阿魏酸的功能和应用. 欧仕益.广州食品工业科技，第18卷第4期. 2002 * |
| 青藤碱对核转录因子κB及其抑制因子IκB的影响. 金晓琨等，2004，20（7）：788－791.中国药理学通报，第20卷第7期. 2004 |
| 青藤碱对核转录因子κB及其抑制因子IκB的影响. 金晓琨等，2004，20(7)：788-791.中国药理学通报，第20卷第7期. 2004 * |
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| CN1981763A (en) | 2007-06-20 |
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