CN100577161C - New application of dendrobine - Google Patents
New application of dendrobine Download PDFInfo
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- CN100577161C CN100577161C CN200610028993A CN200610028993A CN100577161C CN 100577161 C CN100577161 C CN 100577161C CN 200610028993 A CN200610028993 A CN 200610028993A CN 200610028993 A CN200610028993 A CN 200610028993A CN 100577161 C CN100577161 C CN 100577161C
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Abstract
The invention discloses two novel purposes of dendrobine, namely applications in preparation of drug for preventing or treating arthritis and protecting gastrointestinal mucosa from lesion.
Description
Technical field
The present invention relates to the new application of dendrobine (Dendrobine), particularly in prevention or treatment of arthritis disease, and the application of protection gastrointestinal mucosal damage aspect.
Background technology
Dendrobine (Dendrobine) is as a kind of chemical constituent, separates first in 1932 to obtain (H.Suzuki, et al.:YakugakuZasshi, 52,996,1049 (1932) from Chinese crude drug Dendrobium nobile (Dendrobium nobile Lindl.); 54,801 (1934) .), clear and definite its extraction separation method in 1962, and prove conclusively its complete chemical constitution (T.Okamoto, et al.The structure of dendrobine.Chem.Pharm.Bull., 1964,12 (4): 506-512; Y.Inubushi, et al.Isolation andCharacterization of Alkaloids of the Chinese Drug " Chin-Shih-Hu " .Chem.Pharm.Bull., 1964,12 (10): 1175-1180), its chemical constitution is as shown in the formula shown in the I, and molecular formula is C
16H
25NO
2, molecular weight is 263.
Show that according to existing literature retrieval the pharmacological action of dendrobine has the following aspects: 1, can suppress the activity of isolated rabbit intestinal, and there is contraction in the Cavia porcellus uterus of exsomatizing; 2, heavy dose of dendrobine can reduce the myocardial contraction of rabbit, Cavia porcellus, brings high blood pressure down and suppress to breathe; 3, faint pain relieving antipyretic effect (Cheng Ke-hui, et al.J Pharmacol Exper Therap, 1936,55 (3): 310 are arranged; Henry M L, et al.J Pharmacol Exper Therap, 1936,56 (4): 466).Other pharmacological research of this composition is not seen that any report is arranged.
Dendrobium nobile (Dendrobium nobile Lindl.) is the main source of occurring in nature dendrobine.The inventor discovered once that the Dendrobium nobile medicinal substances extract had prevention or treatment of arthritis disease, and the effect (publication number is the patent application of CN1533801) of protection gastrointestinal mucosal damage.But because the complicated component in the above-mentioned Dendrobium nobile extract wherein contains multiple alkaloid and other chemical constituent, so the material base of indeterminate its drug action also, the i.e. effective ingredient of clear and definite pharmacological action not.
Summary of the invention
The inventor is the effective site of further screening in the Dendrobium nobile extract; find through a large amount of research work and pharmacological testing; formula I chemical compound dendrobine also has prevention or treatment of arthritis disease; and the effect of protection gastrointestinal mucosal damage, and the relevant curative effect of disclosed Dendrobium nobile extract is better in the more above-mentioned patent documentation.Therefore, the purpose of this invention is to provide the new application of formula I chemical compound dendrobine aspect above-mentioned two.
The present invention test shows, formula I chemical compound dendrobine has the effect that suppresses acute inflammation and rat assist agent arthritis due to the rat carrageenan, and presents certain dose-effect relationship.Therefore, dendrobine can be used for prevention or treatment of arthritis disease.
Experiment simultaneously also shows, formula I chemical compound dendrobine has the effect of chronic gastric ulcer due to the acute digestive tract ulcer that suppresses due to the rat dehydrated alcohol and the acetic acid simultaneously.Therefore, dendrobine can be used for protecting the acute or chronic injury of gastrointestinal mucosal, the acute and chronic digestible road ulcer especially for control.
In sum, dendrobine 2-40mg/kg can produce the preventive and therapeutic effect of above-mentioned two aspects, under similar experimental condition, needs the effective dose of 4-5g crude drug/kg obviously to reduce than the Dendrobium nobile extract.In addition, treatment of arthritis non-steroidal anti-inflammatory drug commonly used all can cause the digestive tract damage as ibuprofen, Diclofenac etc. at present, so need usually to take with gastric mucosa protectants such as ranitidines; Dendrobine has the effect of antiinflammatory and protection gastric mucosa injury simultaneously, but has competitive advantage.
The specific embodiment
Further specify the present invention with embodiment below, but the present invention is not limited.
The extraction separation of embodiment 1 formula I chemical compound dendrobine
According to above-mentioned document (T.Okamoto, et al.The structure of dendrobine.Chem.Pharm.Bull., 1964,12 (4): 506-512; Y.Inubushi, et al.Isolation andCharacterization of Alkaloids of the Chinese Drug " Chin-Shih-Hu " .Chem.Pharm.Bull., 1964,12 (10): the method 1175-1180) is carried out extraction separation, and concrete steps are as follows:
Commercially available 1.0kg Dendrobium nobile medical material chopping was flooded two days with methanol 8L, filter, residue extracts (each 5L), merge extractive liquid, 4 times with methanol eddy, concentrating under reduced pressure gets thick extractum, extractum extracts repeatedly with the dissolving of 5% aqueous hydrochloric acid solution, filters, and merges the acid water extract, adding ammonia in ice bath transfers about pH to 11.0, this alkaline aqueous solution, with extracted with diethyl ether repeatedly, combined ether layer solution, filter, reclaim solvent to doing, get the dendrobine crude extract, last alumina column chromatography, with the benzene eluting, substep is collected eluent, and the assembling section eluent reclaims solution to doing, get a pure product chemical compound, the mensuration fusing point is: 134-136 ℃, and to the MS of this chemical compound, H-NMR, spectrum such as C-NMR are resolved, and dendrobine (the being formula I chemical compound) structure of proving conclusively the announcement of its structure and document is in full accord.
Effect embodiment 1
The various dose dendrobine is to acutely inflamed inhibitory action due to the sufficient sole of the foot carrageenin
Experimental technique: rat random packet, every group of 10 animals, preceding 1 hour gastric infusion of Yu Zhiyan, the sterile working, inject 1% carrageenin 0.1ml down for the right back sufficient plantar aponeurosis of rat and cause inflammation, with drainage measure cause scorching before and cause the right back sufficient sole of the foot volume of scorching back different time so that the sufficient volume difference before and after scorching is the swelling value, calculates swelling rate and suppression ratio according to the swelling value.Experimental result sees the following form 1, with the matched group ratio,
* be p＜0.05, * * is p＜0.01.
Swelling rate %=E
n-E
0/ E
N* 100
E
n=cause the swelling value of scorching back different time
E
o=cause the swelling value before scorching
Suppression ratio %=C-T/C * 100
The swelling rate of C=matched group
The swelling rate of T=treatment group
Table 1 various dose dendrobine is to acutely inflamed inhibitory action due to the rat carrageenan
Above experimental result shows: dendrobine truly has the acutely inflamed effect due to the rat carrageenan that suppresses, and strengthens gradually along with the increase of dosage.
Effect embodiment 2
The various dose dendrobine is to the prevention and the therapeutical effect of rat assist agent arthritis
Experimental technique: body weight 180-200g male SD rat, the right back sufficient sole of the foot intradermal injection Freund's complete adjuvant 0.1ml of every Mus causes inflammation, begin gastric infusion next day, every day 1 time, continuous 20 days, with drainage measure cause scorching before and cause the pedal swelling volume of scorching back different number of days, and calculate swelling rate and suppression ratio, and compare with method of inspection medication group and model control group.Experimental result sees the following form 2, and with the matched group ratio, * is p＜0.05, and * * is p＜0.01.
Experimental result shows: during the dosage of dendrobine 2mg/kg rat assist agent arthritis is produced certain inhibitory action, and along with the increase of dosage, inhibitory action is strengthened.
Effect embodiment 3
The various dose dendrobine is to the influence of the acute gastric mucosal lesion due to the rat dehydrated alcohol
Experimental technique: SD rat random packet, fasting 48 hours is freely drunk water.Only gavage dehydrated alcohol 1ml/ during experiment, gavaging last hour gastric infusion of dehydrated alcohol, put to death animal in 3 hours behind the clothes dehydrated alcohol, dissect and get stomach, fix with 1% formalin, degree of injury is represented with ulcer index, the length of streak damage is measured its length greater than 1mm person, and every mm note 1 minute is if its length width is kept the score it greater than 1mm person and doubled, keeping the score adds up to the ulcer index of this animal, and every compares.Experimental result sees the following form 3, and with the matched group ratio, * is p＜0.05, and * * is p＜0.01.
Table 3 various dose dendrobine is to the inhibitory action of acute gastric mucosal lesion due to the rat dehydrated alcohol
Above experimental result shows: dendrobine has the effect that suppresses the acute digestive tract ulcer due to the rat dehydrated alcohol, during the dosage of its 40mg/kg and almost being equal to of ranitidine (50mg/kg).
Effect embodiment 4
The various dose dendrobine burns the influence of type chronic gastric ulcer to rat acetic acid
Experimental technique: SD rat limosis 24 hours, freely drink water, under the anesthesia of 3% pentobarbital sodium, open the abdominal cavity, under the stomach serous coat, inject 30% glacial acetic acid 0.1ml, sew up immediately, play gastric infusion next day, every day 1 time, continuous 10 days.Stomach is got in dissection, uses formaldehyde fixed, measures the ulcer area, carries out comparing between each group.Experimental result sees the following form 4, and with the matched group ratio, * * is p＜0.01.
Table 4 various dose dendrobine burns the influence of type chronic gastric ulcer to rat acetic acid
Above experimental result shows: dendrobine has the effect that suppresses the rat chronic gastric ulcer.
Claims (1)
1, formula I chemical compound dendrobine
Application in the medicine of preparation prevention or treatment of arthritis disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610028993A CN100577161C (en) | 2006-07-14 | 2006-07-14 | New application of dendrobine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610028993A CN100577161C (en) | 2006-07-14 | 2006-07-14 | New application of dendrobine |
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| CN2009101405593A Division CN101543492B (en) | 2006-07-14 | 2006-07-14 | Novel application of dendrobine |
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|---|---|
| CN101103974A CN101103974A (en) | 2008-01-16 |
| CN100577161C true CN100577161C (en) | 2010-01-06 |
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| CN200610028993A Expired - Fee Related CN100577161C (en) | 2006-07-14 | 2006-07-14 | New application of dendrobine |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101407558B (en) * | 2008-11-14 | 2011-02-02 | 浙江大学 | Preparation of Dendrobium nobile polysaccharide extract and use there |
| CN102188621B (en) * | 2011-05-12 | 2013-05-01 | 中国药科大学 | Application of total dendrobium crepidatum alkaloids in preparing medicament for treating acute and chronic inflammation, acute and chronic arthritis or rheumatoid arthritis diseases |
| CA2918340C (en) * | 2013-07-17 | 2023-01-03 | The Hong Kong University Of Science And Technology | Rhynchophylline derivatives and their use as epha4 inhibitors for neuroprotection |
| CN108784201A (en) * | 2018-08-17 | 2018-11-13 | 深圳长元知识产权服务有限公司 | Traditional Chinese medicine medical pillow |
| CN111135168A (en) * | 2020-01-02 | 2020-05-12 | 南方医科大学 | Application of dendrobine in preparing osteoclast differentiation inhibitor |
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