CN104138367B - The purposes of Kosteletzkya virginica element in preparation control inflammation related disease medicine - Google Patents
The purposes of Kosteletzkya virginica element in preparation control inflammation related disease medicine Download PDFInfo
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- CN104138367B CN104138367B CN201410399929.6A CN201410399929A CN104138367B CN 104138367 B CN104138367 B CN 104138367B CN 201410399929 A CN201410399929 A CN 201410399929A CN 104138367 B CN104138367 B CN 104138367B
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- 241000982152 Kosteletzkya virginica Species 0.000 title claims abstract description 47
- 206010061218 Inflammation Diseases 0.000 title claims abstract description 27
- 230000004054 inflammatory process Effects 0.000 title claims abstract description 27
- 201000010099 disease Diseases 0.000 title abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 13
- 239000003814 drug Substances 0.000 title abstract description 12
- 238000002360 preparation method Methods 0.000 title description 6
- 239000000126 substance Substances 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 24
- 230000002757 inflammatory effect Effects 0.000 abstract description 12
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 abstract description 7
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 abstract description 6
- 206010040070 Septic Shock Diseases 0.000 abstract description 6
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 abstract description 6
- 241000699670 Mus sp. Species 0.000 abstract description 5
- 208000015122 neurodegenerative disease Diseases 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
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- 201000003068 rheumatic fever Diseases 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 2
- 239000000178 monomer Substances 0.000 abstract description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 206010014025 Ear swelling Diseases 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000007779 soft material Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
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- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- FZZNNPQZDRVKLU-YTFOTSKYSA-N Cadinane Chemical compound C1C[C@H](C)C[C@H]2[C@H](C(C)C)CC[C@H](C)[C@@H]21 FZZNNPQZDRVKLU-YTFOTSKYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 241000082085 Verticillium <Phyllachorales> Species 0.000 description 1
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- 239000012228 culture supernatant Substances 0.000 description 1
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- 210000005069 ears Anatomy 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
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- -1 hydroxypropyl Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940089151 indomethacin 20 mg Drugs 0.000 description 1
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- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
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- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
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- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
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Abstract
The invention belongs to natural medicine field, relate to the application of special monomer Kosteletzkya virginica element in pharmaceutical compositions in Kosteletzkya virginica, the application especially in the pharmaceutical composition preparing inflammation related disease.The present invention is by external inflammatory model experimentation, and result shows the prostaglandin E that described Kosteletzkya virginica element can reduce inflammation-induced
2generation and nitric oxide production release; Zoopery finds, the mice ear that Kosteletzkya virginica element can suppress phorbol exters to stimulate.Experiment confirms, described Kosteletzkya virginica element has obvious antiinflammatory action to inflammation related disease, can prepare the medicine of control inflammation related disease.Described diseases associated with inflammation comprises rheumatic arthritis, inflammatory bowel, neurodegenerative disease, septic shock etc.
Description
one, technical field:
The present invention relates to natural medicine field, be specifically related to the application of special monomer Kosteletzkya virginica element (virginicin) in pharmaceutical compositions in Kosteletzkya virginica, the application especially in the pharmaceutical composition of preparation control inflammation related disease.
two, technical background:
Inflammatory reaction is one of important component part of body immune system, and body carries out accurate regulation and control by number of ways to it.But when inflammatory reaction is uncontrollable, body various diseases can be caused, as rheumatoid arthritis (rtheumatoidarthriti), inflammatory bowel (Inflammatoryboweldisease, IBD), neurodegenerative disease (neurodegenerativedisorder) and septic shock (septicshocksyndrome) etc., long-term inflammatory reaction stimulates also can bring out body canceration (1, Zhuetal, CancerBiolTher, 2011, 12 (2): 95-105), these all serious threat the physical and mental health of people, therefore it is that the Main way of these disease medicaments is treated in exploitation at present that too drastic to body inflammatory reaction control effectively.Research shows, prostaglandin E
2(PGE
2), the inflammatory factor such as nitric oxide (NO) can be induced to express in inflammatory reaction, thus aggravation body degree of inflammation (2, RicciottiEandFitzGeraldGA, ArteriosclerThrombVascBiol, 2011,31 (5): 986-1000), therefore the inflammatory reaction by contributing to improving body is suppressed to these inflammatory factors.
Kosteletzkya virginica (Kosteletzkyavirginica (L.) Presl.) is the perennial root plant that Malvaceae Kosteletzkya virginica belongs to.Kosteletzkya virginica natural distributed is coastal from the Delaware State to the sabkha littoral zone of Texas in eastern united states, at present in Liaoning, Jiangsu, Shandong etc. economizes Coastal beach plantation.The underground tuber of Kosteletzkya virginica is flourishing especially, and along with the prolongation of growth year, fleshy tap root can constantly expand, the custom of the Indian original inhabitants in eastern united states its treatment upper respiratory tract infection useful, but its treatment respiratory inflammation material base has no report.Kosteletzkya virginica element is from the underground tuber of Kosteletzkya virginica, be separated a kind of cadinane type sesquiterpene obtained, and to verticillium dahliae, there is killing action, can be used for cotton verticillium wilt control (3, Chen Yu, number of patent application: 201310211385.1), but the plain effect to aspect of inflammation of Kosteletzkya virginica is there are no report.
three, summary of the invention:
Kosteletzkya virginica element is the object of the present invention is to provide to prepare the application of inflammation inhibitor, the application particularly in the diseases associated with inflammation medicine that mediated by inflammatory factor in preparation treatment endotoxin shock etc. of Kosteletzkya virginica element.
From list of references [3], the chemical formula of described Kosteletzkya virginica element is C
16h
18o
5, molecular weight is 290, and chemical structural formula is:
Described Kosteletzkya virginica element can be used for preparing the diseases associated with inflammation medicine for the treatment of endotoxin shock etc. and being mediated by inflammatory factor.
Described diseases associated with inflammation comprises rheumatic arthritis, inflammatory bowel, neurodegenerative disease, septic shock etc.
Through pharmacological evaluation confirm Kosteletzkya virginica element can effectively the inflammation-inhibiting factor as prostaglandin E
2(PGE
2) and the expression of nitric oxide (NO); In addition, 40mg/kg Kosteletzkya virginica element has obvious inhibitory action to phorbol exters induced mice ear swelling, suitable with positive control Indomethacin's effect.Can be used as the medicine of the diseases associated with inflammation that inflammation inhibitor is mediated by inflammatory factor for the preparation for the treatment of rheumatic arthritis, inflammatory bowel, neurodegenerative disease, septic shock etc.
The invention provides Kosteletzkya virginica element and be prepared into pharmaceutical composition and preparation thereof with medically acceptable pharmaceutic adjuvant.As, tablet, pill, unguentum, capsule, oral liquid, granule and injection injectable powder or liquid drugs injection liquid.
four, accompanying drawing illustrates:
Can be used as APPENDIX MATERIALSThe with figure below to report.
The molecular structural formula of Fig. 1 Kosteletzkya virginica element.
Fig. 2 Kosteletzkya virginica element acts on the MTT experiment result figure after RAW264.7 cell.
Fig. 3 Kosteletzkya virginica element suppresses prostaglandin E
2(PGE
2) effect.
#p<0.01vs matched group;
*p<0.01vsLPS processed group.
The effect of Fig. 4 Kosteletzkya virginica element inflammation-inhibiting factor nitric oxide (NO).
#p<0.01vs matched group;
*p<0.01vsLPS processed group.
five, detailed description of the invention:
In conjunction with detailed description of the invention, the invention will be further described, but content of the present invention is not restricted to cited embodiment.
Embodiment 1 Kosteletzkya virginica element cell toxicity test
Adopt mtt assay to detect the cytotoxicity of Kosteletzkya virginica element, concrete steps are as follows:
By RAW264.7 cell (2 × 10
5individual cells/well) access 96 well culture plate overnight incubation, add Kosteletzkya virginica element (10,20,40,60,80,100 μm of ol/L of variable concentrations, with DMSO as blank) combined effect 24h, then MTT to final concentration 0.5mg/ml effect 3h is added, DMSO is added by 100 μ l/ holes, concussion 15min, reads absorbance at 570nm wavelength place.
OD
570the growing state of cell can be reflected, according to OD
570calculate cell survival rate, thus judge whether Kosteletzkya virginica element exists cytotoxicity.
Mtt assay testing result shows (see Fig. 2): Kosteletzkya virginica element does not substantially have cytotoxicity to RAW264.7 cell under 10 ~ 100 μm of ol/L concentration conditions.
Embodiment 2 Kosteletzkya virginica element suppresses prostaglandin E
2(PGE
2) effect
The mouse macrophage RAW264.7 of trophophase of taking the logarithm spreads 24 orifice plates, attach overnight, adds shore Radix Malvae sylvestris element or positive control Indomethacin, adds the LPS process 24h of 100ng/ml after 2h.Collecting cell culture fluid, 1000g, 15min, adopt the prostaglandin E in Inhibition ELISA detection supernatant
2.The results are shown in Figure 3.
Compared with the inflammatory model group of inducing with LPS, after giving shore Radix Malvae sylvestris element, the prostaglandin E that LPS inducing mouse macrophage RAW264.7 secretes
2obvious minimizing, and in dose dependent.
Embodiment 3 Kosteletzkya virginica element inflammation-inhibiting factor nitric oxide (NO) effect
By RAW264.7 cell (1 × 10
6cell/mL) access 96 well culture plate overnight incubation, then Kosteletzkya virginica element (10,20,40,60,80,100 μm of ol/L of variable concentrations are added, with DMSO as blank), the LPS adding 100ng/ml after 2h stimulates 24h, collecting cell culture supernatant, detects the content of nitric oxide (NO) by Griess method.
Experimental result (see Fig. 4) shows: Kosteletzkya virginica element can nitric oxide in the lipopolysaccharide-induced RAW264.7 cell of anti-bacteria, and in dose dependent, IC
50value is 17.72 μMs.
The effect of embodiment 4 pairs of Mice Auricle phorbol exters inflammatory models
Healthy male ICR mouse 60, body weight 18 ~ 22g, is divided into following 5 groups at random, often organizes 12: (1) matched group, 0.5%CMC-Na, ig; (2) positive drug, indomethacin 20mg/kg, ig; (3) tested material high dose, 40mg/kg, ig; (4) dosage in tested material, 20mg/kg, ig; (5) tested material low dosage, 10mg/kg, ig.Adapted to raise through 5 days, each group mice overnight fasting before test.1 μ g phorbol exters is dissolved in 20 μ l acetone, is respectively coated with phorbol exters 10 μ l/ only for causing scorching ear in mouse right ear both sides, and it is non-ly cause scorching ear that left ear does not do any process.After causing scorching 0.5h, the corresponding test medicine of each group gavage.After administration 6h, dead 12 animals in every component other places, cut two ears, get circular auricle respectively, use scales/electronic balance weighing with the card punch of diameter 8mm from same area.Represent swelling with left and right auricle weight difference, the results are shown in Table 1.
the plain impact on phorbol exters induced mice ear swelling of table 1 Kosteletzkya virginica ( ± S, n=12
)
| Group | Dosage (mg/kg) | Ear swelling degree (mg) | Suppression ratio (%) |
| Matched group | - | 19.6±2.47 | - |
| Indomethacin group | 20 | 9.5±1.26 * | 51.53 |
| Tested material low dosage | 10 | 14.53±1.18 * | 25.87 |
| Dosage in tested material | 20 | 11.72±1.69 * | 40.20 |
| Tested material high dose | 40 | 9.14±1.43 * | 53.37 |
Compare with matched group,
*p<0.01
Embodiment 5 is containing the tablet of Kosteletzkya virginica element of the present invention
Kosteletzkya virginica element 100mg and starch 50mg, dextrin 50mg that Example 1 obtains mix, and make wetting agent with appropriate 30% ethanol, make soft material, conventional method is granulated, and adds the mixing of appropriate magnesium stearate, makes tablet.
Embodiment 6 is containing the capsule of Kosteletzkya virginica element of the present invention
Get Kosteletzkya virginica element 50mg and starch 70mg, dextrin 10mg, Icing Sugar 10mg to mix, make wetting agent with appropriate 30% ethanol, make soft material, conventional method is granulated, and loads in hard capsule.
Embodiment 7 is containing the slow releasing capsule of Kosteletzkya virginica element of the present invention
Get Kosteletzkya virginica element 80mg and hydroxypropyl emthylcellulose K15M120mg, ethyl cellulose 45cps40mg, lactose 40mg to mix, appropriate with 10% vinylpyrrolidone k30 alcoholic solution, make soft material, conventional method is granulated, and loads in hard capsule and makes slow releasing capsule.
Claims (1)
1. Kosteletzkya virginica element is preparing the application of inflammation inhibitor, and the chemical formula of described Kosteletzkya virginica element is C
16h
18o
5, molecular weight is 290, and chemical structural formula is:
Kosteletzkya virginica element.
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| CN102229631B (en) * | 2011-05-03 | 2014-06-18 | 西安瑞联近代电子材料有限责任公司 | Method for separating and purifying malvidin glucoside from grape-skin red |
| CN103540492A (en) * | 2012-07-14 | 2014-01-29 | 南京大学连云港高新技术研究院 | Kosteletzkya virginica dry root tuber wine and preparation method thereof |
| CN103351289B (en) * | 2013-05-31 | 2015-03-25 | 江苏省中国科学院植物研究所 | New Kosteletzkya virginica sesquiterpene compound, and preparation method and use thereof |
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