CN1163253C - Mulberry mistletoe extract for preventing or treating anaphylactic reaction, medicinal composition containing it and its preparing process - Google Patents
Mulberry mistletoe extract for preventing or treating anaphylactic reaction, medicinal composition containing it and its preparing process Download PDFInfo
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- CN1163253C CN1163253C CNB001193031A CN00119303A CN1163253C CN 1163253 C CN1163253 C CN 1163253C CN B001193031 A CNB001193031 A CN B001193031A CN 00119303 A CN00119303 A CN 00119303A CN 1163253 C CN1163253 C CN 1163253C
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Abstract
The present invention relates to a loranthus parasiticus extract for preventing and treating anaphylactic reaction, a medical composition containing the loranthus parasiticus extract, the application of the loranthus parasiticus extract in preparing a medicine for treating anaphylactic reaction, and a preparation process of the loranthus parasiticus extract.
Description
The present invention relates to be used to prevent or the Herba Taxilli extract of antianaphylaxis, contain its pharmaceutical composition, Herba Taxilli extract is used for the purposes of the medicine of antianaphylaxis and the preparation method of Herba Taxilli extract in preparation.
I allergic reaction type or title type are common clinically allergy, and sickness rate is higher.China has irritated patient about 10,000,000 approximately.Anaphylactic disease comprises: 1, the anaphylactic shock that causes of medicine and serum, show as respiratory symptoms such as uncomfortable in chest, out of breath, dyspnea, and be in a cold sweat, circulatory failure symptoms such as pale complexion, thready pulse speed, blood pressure drops, severe patient can be dead rapidly because of anaphylactic shock; 2, respiratory tract anaphylaxis reaction, typical disease is bronchial asthma and allergic rhinitis, and the former bronchial muscular spasm and pulmonary vascular expansion, permeability strengthen and asthma and dyspnea, latter's nasal mucosa edema occur, secretion increases, and symptoms such as watery nasal discharge, sneeze occur.3, phagopyrism (allergic reaction of alimentary canal) because gastrointestinal absorbs unusually, causes symptoms such as urticaria, stomachache, diarrhoea, vomiting, and severe patient also anaphylactic shock can occur.4, skin allergy shows as eczema, urticaria and vasodilation.
The I-allergic reaction type causes by anaphylactogen, and morbidity is divided into three phases, promptly the sensitization stage, send out quick stage and effective stage.
The sensitization stage: anaphylactogen also claims allergen to enter body by respiratory tract, digestive tract or mucocutaneous etc., stimulates body to produce antibody, and the IgE antibody-like causes the I-allergic reaction type.
Send out quick the stage: when identical anaphylactogen enters body once more, can combine, cause taking off the granule reaction, disengage multiple medium with the IgE on the mast cell membrane.Bonded IgE is intensive on irritated patient's the cell membrane, and anaphylactogen might fall within on the Fab section of adjacent IgE, forms " bridging "." bridging " causes rapidly discharging the granule of storage, has a series of secondary medium to be synthesized out again simultaneously, meanwhile also has some enzymes to be released.Early stage what send out the stage quick, the FcR gathering can cause the activation of a series of variation, particularly Protein kinase C and the inhibition of protein kinase A.
Effective stage: sending out the stage quick makes mast cell degranulation, discharges multiple medium, comprises histamine, leukotrienes chemical compound, kassinin kinin and prostaglandin etc., because irritated patient's release medium is too quickly, too much, makes body produce a series of symptom.Anaphylaxis is mainly by Drug therapy, and the medicine sodium cromoglicate that these medicines have three classes: a. to suppress medium release substantially can be stablized mast cell membrane, anti-anti-avulsion particle release medium.Epinephrine, ephedrine, aminophylline can improve cell c-AMP, suppress degranulation; B. antihistaminics such as the antagonist diphenhydramine of medium, promethazine.Epinephrine shrinks peripheral blood vessel, and expansion bronchus is used for the salvage drug anaphylactic shock; C. other glucocorticoid, calcium gluconate, calcium chloride are used to alleviate telangiectasis and reduce permeability.Clinical main use promethazine class medicine, its shortcoming is drowsiness.Sodium cromoglicate does not use substantially owing to the drug effect difference.Herba Taxilli belongs to the antirheumatic class in Chinese medicine, not seeing has antianaphylactic report.
The inventor finds that now Herba Taxilli has the Profilin kinase c and improves the content ability of cell c-AMP, and Herba Taxilli itself just has the effect of c-AMP sample, can activated protein kinase A.Meanwhile it can stablize mast cell membrane, and the release of control medium also has sodium cromoglicate and the effect of aminophylline two class medicines, therefore can suppress anaphylactoid better and send out quick the stage, the present invention is based on above-mentioned discovery and is accomplished.
The present invention seeks to seek and develop the novel medical use of Chinese medicine Herba Taxilli.
First aspect present invention relates to and is used to prevent or the Herba Taxilli extract of antianaphylaxis.
Further aspect of the present invention relates to and is used to prevent or the pharmaceutical composition of antianaphylaxis, and it comprises Herba Taxilli extract and pharmaceutical carrier or excipient.
Further aspect of the present invention relates to Herba Taxilli extract and is used for preventing or the medicine purposes of antianaphylaxis in preparation.
The invention still further relates to the method for prevention or antianaphylaxis, it comprises that the Herba Taxilli extract with prevention or treatment effective dose needs prevention or treats anaphylactoid patient.
The invention still further relates to the preparation method of Herba Taxilli extract, it comprises:
I) with the powdery Herba Taxilli organic solvent extraction that is selected from petroleum ether, ethane, dichloromethane, chloroform, benzene or toluene, remove liposoluble substance, filter, discard filtrate, keep filter cake,
Ii) with i) the middle filter cake organic solvent extraction that is selected from alcohol or ketone, filter, discard filter cake, filtrate decompression concentrates, and gets Herba Taxilli extract, or carries out ii) described extraction earlier, carries out i again) described extraction, get the Herba Taxilli extract of wanting;
Iii) as need, with the Herba Taxilli extract that obtains above by macroporous adsorbent resin and cellulose column purification.
According to the present invention, the Herba Taxilli extract before the purification of the present invention contains alkaloid (by bismuth potassium iodide reaction proof), and the Herba Taxilli extract behind the purification only contains alkaloid.Further, the ultra-violet absorption spectrum that the present invention only contains the methanol solution of alkaloidal Herba Taxilli extract shows, its peak value is positioned at 278nm and (sees Fig. 1, the ultraviolet spectra of Herba Taxilli extract), high pressure liquid phase analysis (the reverse post of C-18 that only contains the methanol solution 20 μ l of alkaloidal Herba Taxilli extract, detect wavelength 254nm) show that its retention time is 2.56 minutes (seeing Fig. 2, the high-pressure liquid phase collection of illustrative plates of Herba Taxilli extract).
According to the present invention, " anaphylaxis " of the present invention refers to I allergic reaction type or type.
According to the present invention, used in the inventive method " alcohol " can for example be methanol, ethanol or propanol etc.; Used " ketone " can for example be acetone, butanone etc.
Therefore the present invention also relates to and containing as the Herba Taxilli extract of the effective dose of active ingredient and the pharmaceutical composition of conventional medicine excipient or adjuvant.Usually pharmaceutical composition of the present invention contains the Herba Taxilli extract of 0.1-90 weight %.Pharmaceutical composition can prepare according to methods known in the art.When being used for this purpose, if desired, Herba Taxilli extract and one or more solids or liquid medicine excipient and/or adjuvant can be combined, make the suitable administration form or the dosage form that can be used as human.
Herba Taxilli extract of the present invention or contain its pharmaceutical composition can the unit dosage form administration, route of administration can be intestinal or non-intestinal, as oral, muscle, subcutaneous, nasal cavity, oral mucosa, skin, peritoneum or rectum etc.Form of administration is tablet, capsule, drop pill, aerosol, pill, powder, solution, suspensoid, Emulsion, granule, liposome, transdermal agent, buccal tablet, suppository, lyophilized injectable powder etc. for example.Can be ordinary preparation, slow releasing preparation, controlled release preparation and various particulate delivery system.For the unit form of administration is made tablet, can be extensive use of various carrier well known in the art.Example about carrier is, for example diluent and absorbent are as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, carbamide, calcium carbonate, kaolin, microcrystalline Cellulose, aluminium silicate etc.; Wetting agent and binding agent are as water, glycerol, Polyethylene Glycol, ethanol, propanol, starch slurry, dextrin, syrup, Mel, glucose solution, mucialga of arabic gummy, gelatine size, sodium carboxymethyl cellulose, lac, methylcellulose, potassium phosphate, polyvinylpyrrolidone etc.; Disintegrating agent, for example dry starch, alginate, agar powder, laminaran, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitol fatty acid ester, dodecyl sodium sulfate, methylcellulose, ethyl cellulose etc.; Disintegrate inhibitor, for example sucrose, glyceryl tristearate, cocoa butter, hydrogenation wet goods; Absorption enhancer, for example quaternary ammonium salt, sodium lauryl sulphate etc.; Lubricant, for example Pulvis Talci, silicon dioxide, corn starch, stearate, boric acid, liquid paraffin, Polyethylene Glycol etc.Tablet further can also be made coated tablet, for example sugar coated tablet, thin membrane coated tablet, ECT, or double-layer tablet and multilayer tablet.For pill is made in the administration unit, can be extensive use of various carrier well known in the art.Example about carrier is, for example diluent and absorbent are as glucose, lactose, starch, cocoa butter, hydrogenated vegetable oil, polyvinylpyrrolidone, Gelucire, Kaolin, Pulvis Talci etc.; Binding agent such as arabic gum, Tragacanth, gelatin, ethanol, Mel, liquid sugar, rice paste or batter etc.; Disintegrating agent is as agar powder, dry starch, alginate, dodecyl sodium sulfate, methylcellulose, ethyl cellulose etc.For suppository is made in the administration unit, can be extensive use of various carrier well known in the art.Example about carrier is, for example the ester of Polyethylene Glycol, lecithin, cocoa butter, higher alcohol, higher alcohol, gelatin, semi-synthetic glyceride etc.For capsule is made in the administration unit, the effective ingredient Herba Taxilli extract is mixed with above-mentioned various carriers, and the mixture that will obtain thus places hard obviously capsule or soft capsule.Also the effective ingredient Herba Taxilli extract can be made microcapsule, be suspended in and form suspensoid in the aqueous medium, in the hard capsule of also can packing into or make injection and use.For injection preparation is made in the administration unit, as solution, Emulsion, lyophilized injectable powder and suspensoid, can use this area all diluent commonly used, for example, water, ethanol, Polyethylene Glycol, 1, the isooctadecanol of ammediol, ethoxylation, the isooctadecanol of polyoxyization, Polyoxyethylene Sorbitol Fatty Acid Esters etc.In addition, ooze injection, can in injection preparation, add proper amount of sodium chloride, glucose or glycerol, in addition, can also add conventional cosolvent, buffer agent, pH regulator agent etc. in order to prepare etc.
In addition, as needs, also can in pharmaceutical preparation, add coloring agent, antiseptic, spice, correctives, sweeting agent or other material.
The dosage of Herba Taxilli extract of the present invention depends on many factors, for example to prevent or treat the character and the order of severity of hypersensitivity disorders, the sex of patient or animal, age, body weight and individual reaction, used particular compound, route of administration and administration number of times etc.Above-mentioned dosage can the single dose form or be divided into several, for example two, three or four dosage form administrations.
The following examples and biological activity test are used for further specifying the present invention, but this and do not mean that any limitation of the invention.
The preparation of embodiment 1 Herba Taxilli extract
1kg Herba Taxilli fecula, the dichloromethane that adds 3 times of amounts soaks, and defat is soaked repeatedly for several times, removes fat-soluble substances.Filter, discard filtrate, keep filter cake.
The filter cake soak with ethanol several of triplication, sucking filtration, filter cake discards, and filtrate decompression is concentrated into dried, gets Herba Taxilli and slightly carries product 120 grams.
Herba Taxilli crude extract 40 grams are dissolved in the distilled water, by macroporous adsorbent resin, divide decontamination, with ethanolysis absorption, collect eluent, and evaporated under reduced pressure gets product Herba Taxilli extract 3.4 grams.
The said extracted thing is dissolved in methanol, by cellulose column, with the tertiary sodium phosphate eluting of 0.05M, collects second colour band, eluent is removed tertiary sodium phosphate, obtains purified Herba Taxilli extract 0.33 gram.
Herba Taxilli 1kg is slightly carried product 120g, and first step purification gets 11.2g, and the second step purification obtains 1g, total recovery 0.1%.
Biological activity:
One Herba Taxilli extract suppresses the activity of cell protein kinase c
Herba Taxilli extract suppresses the foamable reaction of erythroleukemia K-562 cell
With the K-562 cell culture on 96 well culture plates, when activating with protein kinase C activation agent phorbol ester, vesicle appears in cell membrane, the inhibitor of Protein kinase C can suppress the formation of vesicle, the results are shown in Table 1, can see that by data in the table 1 Herba Taxilli extract can suppress the K-562 cell significantly and be subjected to phorbol ester to stimulate the vesicle that forms.Therefore, Herba Taxilli extract is the inhibitor of Protein kinase C.
Check with the PKC analytical system of human leukemia cell HL-60 the activity of Herba Taxilli extract to the results are shown in Table 2 that can see that by table 2 Herba Taxilli extract also has the obvious suppression effect to the Protein kinase C of HL-60 cell, suppression ratio reaches 68%.
Two Herba Taxilli extracts improve the activity of cell protein kinases A
1. Herba Taxilli extract can improve 6.94 times of the content of the c-AMP of erythroleukemia K-562 cell.Concrete outcome sees Table 3.
2. Herba Taxilli extract can show the activity of c-AMP under acellular situation, the results are shown in Table 4, and table 4 explanation Herba Taxilli extract itself just has the effect of " c-AMP " sample.
3. Herba Taxilli extract has remarkable potentiation to the activity of protein kinase A among the human leukemia HL-60 cell, the results are shown in Table 5, and data declaration Herba Taxilli extract 80 μ g/ml can improve active 4.22 times of protein kinase A in the table 5.
Three. Herba Taxilli extract suppresses rat hypertrophy cell and takes off granule: Herba Taxilli extract can improve c-AMP level in the cell, activated protein kinase A, the while can be suppressed the activity of intracellular protein kinase c, illustrates that it can stabilizing cell membrane.The mast cell degranulation reaction is anaphylactoid important step.The medicine of stablizing the cell membrane of mastocyte can be used for control hypersensitive.
1. what Herba Taxilli extract can suppress rat hypertrophy cell significantly takes off granule reaction, and is dose-dependence, the results are shown in Table 6, can see that by table 6 the Herba Taxilli extract half-inhibition concentration is 10.28 μ g/ml.
2. Herba Taxilli extract suppresses degranulated ability and obviously is better than the positive control drug sodium cromoglicate, under identical dosage, is 1.9 times of sodium cromoglicate.The results are shown in Table 7.
The influence that table 1 Herba Taxilli extract forms the inductive K-562 cell vesicle of phorbol ester
Group control cells cell+phorbol ester cell+Herba Taxilli extract
+ phorbol ester
Cell number 10
410
410
4
Visual assessment-++ +++
Table 2 Herba Taxilli extract is to the active influence of HL-60 born of the same parents' PKC
Active suppress (%) of the total PKC of group
(pmol/min)
Control cells 0.2448-
Herba Taxilli extract (80 μ g/ml) 0.0773 68.42
Herba Taxilli extract (40 μ g/ml) 0.1460 40.36
Table 3 Herba Taxilli extract is to the influence of c-AMP concentration in the K-562 cell
Group c-AMP increases and decreases multiple
pmol/40ul
Contrast 0.209-
Herba Taxilli extract group 1.45 6.93
Sodium cromoglicate group 0.163 0.78
" c-AMP sample " effect of table 4 Herba Taxilli extract
Herba Taxilli extract dosage and conjugated protein bonded amount and conjugated protein bonded amount
(mg/ml) (increase 30ul standard c-AMP)
0.125 1.26 2.33
0.25 2.30 5.97
0.50 4.36 10.67
1.00 10.9 14.14
It is similar to c-AMP to annotate 1 Herba Taxilli extract, can combine with pheron, and be dose-dependence.
Annotating 2 increases standard c-AMP and can increase with pheron and combine, and saturated phenomenon occurs.
Table 5 Herba Taxilli extract is to the influence of the protein kinase A (PKA) of human leukemia cell HL-60
The multiple that the group relative activity increases
Matched group 11.17
Herba Taxilli extract (80 μ g/ml) 47.14 4.22
Herba Taxilli extract (40 μ g/ml) 34.94 3.13
Table 6 Herba Taxilli extract is to the degranulated influence of rat hypertrophy cell (Con A activation)
Group dosage histamine release suppression ratio
μ g/ml (emission photoreading) %
Matched group-36.0
25 9.25 74
Herba Taxilli extract 12.5 15.2 58
6.25 23.45 35
3.125 29.4 18
The relation of dosage and suppression ratio: suppression ratio=0.0014[concentration]
2+ 0.0635[concentration]
Half-inhibition concentration is 10.28 μ g/ml.
Table 7 Herba Taxilli extract and sodium cromoglicate suppress the comparison of mast cell degranulation
Group dosage histamine release suppression ratio P
μ g/ml (emission photoreading) %
Matched group-39.35+/-1.350
Sodium cromoglicate group 25 24.15+/-1.274 38.63
Herba Taxilli extract 25 10.26+/-1.040 73.93＜0.0001
Claims (9)
1. be used to prevent or treat the Herba Taxilli extract of I allergic reaction type or type, it is characterized in that: this extract is following obtaining:
I) with the powdery Herba Taxilli organic solvent extraction that is selected from petroleum ether, dichloromethane, chloroform, benzene or toluene, remove fat-soluble substances, filter, discard filtrate, keep filter cake,
Ii) with i) middle filter cake alcohol that is selected from methanol, ethanol, acetone or the organic solvent extraction that is selected from the ketone of acetone, butanone, filter, discard filter cake, filtrate decompression concentrates, and gets Herba Taxilli extract, or handles in carrying out ii) earlier, carry out i again) handle, get the Herba Taxilli extract of wanting;
Iii) as need, with the Herba Taxilli extract that obtains above by macroporous adsorbent resin and cellulose column purification.
2. be used to prevent or treat the pharmaceutical composition of I allergic reaction type or type, it comprises Herba Taxilli extract and the pharmaceutical carrier or the excipient of claim 1.
3. the Herba Taxilli extract of claim 1, wherein I allergic reaction type or type refer to the I allergic reaction type.
4. the Herba Taxilli extract of claim 1, wherein I allergic reaction type or type refer to type.
5. Herba Taxilli extract is used for preventing or treating the purposes of the medicine of I allergic reaction type or type in preparation.
6. the purposes of claim 5, wherein I allergic reaction type or type are the I allergic reaction types.
7. the purposes of claim 5, wherein I allergic reaction type or type are types.
8. the preparation method of Herba Taxilli extract, it comprises:
I) with the powdery Herba Taxilli organic solvent extraction that is selected from petroleum ether, dichloromethane, chloroform, benzene or toluene, remove fat-soluble substances, filter, discard filtrate, keep filter cake,
Ii) with i) middle filter cake alcohol that is selected from methanol, ethanol, acetone or the organic solvent extraction that is selected from the ketone of acetone, butanone, filter, discard filter cake, filtrate decompression concentrates, and gets Herba Taxilli extract, or handles in carrying out ii) earlier, carry out i again) handle, get the Herba Taxilli extract of wanting;
Iii) as need, with the Herba Taxilli extract that obtains above by macroporous adsorbent resin and cellulose column purification.
9. the method for claim 8, wherein i) in the Herba Taxilli dichloromethane extraction, ii) middle filter cake ethanol extraction.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB001193031A CN1163253C (en) | 2000-06-27 | 2000-06-27 | Mulberry mistletoe extract for preventing or treating anaphylactic reaction, medicinal composition containing it and its preparing process |
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| CNB001193031A CN1163253C (en) | 2000-06-27 | 2000-06-27 | Mulberry mistletoe extract for preventing or treating anaphylactic reaction, medicinal composition containing it and its preparing process |
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| CN1163253C true CN1163253C (en) | 2004-08-25 |
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| CN100586443C (en) * | 2006-07-28 | 2010-02-03 | 福建医科大学附属协和医院 | Application of extractive of parasitic loranthus |
| CN112321479B (en) * | 2020-11-04 | 2022-02-08 | 吉林大学 | Indole-4-formaldehyde compound with antibacterial activity in parasitic loranthus, preparation method and application thereof |
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