CN1299692C - Novel usage of jasminoidin - Google Patents

Novel usage of jasminoidin Download PDF

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CN1299692C
CN1299692C CNB2004100340387A CN200410034038A CN1299692C CN 1299692 C CN1299692 C CN 1299692C CN B2004100340387 A CNB2004100340387 A CN B2004100340387A CN 200410034038 A CN200410034038 A CN 200410034038A CN 1299692 C CN1299692 C CN 1299692C
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jasminoidin
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virus
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medicine
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CN1689581A (en
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崔晓兰
刘发
冯孝章
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Cui Xiaolan
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Abstract

The present invention discloses a new purpose of jasminoidin, namely the application of jasminoidin in preparing medicines for treating viral infectious diseases, including upper respiratory tract infection, viral pneumonia, herpesviral keratitis, herpesviral dermatosis, herpesviral encephalitis, etc. Jasminoidin has inhibiting effect on cytopathy caused by viruses, such as influenza, parainfluenza, herpes simplex, Coxsackie virus, adenovirus, respiratory syncytial virus, etc., and can also inhibit the duplication of viruses. Thus, the jasminoidin has the effect of treating viral pneumonia, herpes simplex viral keratitis, herpesviral dermatosis and herpesviral encephalitis.

Description

The new purposes of jasminoidin
Technical field
The present invention relates to a kind of new purposes of medicine, particularly relate to the new purposes of extracting medicinal Fructus Gardeniae gained jasminoidin.
Background technology
Fructus Gardeniae another name Fructus Gardeniae, Fructus Gardeniae, HUANGGUOSHU etc. are Rubiaceae, belong to the evergreen shrubs plant.Fructus Gardeniae is a conventional Chinese medicine, with the fruit hyoscine, GUIXIN, lung, tri-jiao channel, have functions such as pathogenic fire purging relieving restlessness, clearing away heat-damp and promoting diuresis, removing pathogenic heat from blood and toxic substance from the body, it is vexed to cure mainly calentura, the liver-fire conjunctival congestion, jaundice due to damp-heat; yellow urine is short, heat in blood is told nosebleed, hematuria, jaundice type hepatitis, diseases such as cholecystitis, pyelonephritis, pathopyretic ulcer and favism, external is controlled the congestion that bruise causes and is swollen and ache.
The cape jasmine fruit master contains flavonoid, and other contains crocetin, crocin, and effective ingredient such as ursolic acid, the iridoid glycoside constituents that is wherein contained has choleretic effect.The ethanol extract of fruit and Stigma Croci glycoside, crocetin can make choleresis increase; The extract of Gardenia Ellis fruit has the resistance against diseases of body when improving pancreatitis, improves the function of liver and gastronintestinal system and promotes effects such as pancreatic secretion, alleviate pancreatitis symptom; Geniposide in the fruit of Fructus Gardeniae has the effect of certain antiinflammatory and treatment soft tissue injury.Although Fructus Gardeniae has been as medicinal with a long history, seldom about the applied research of medicinal Fructus Gardeniae extract jasminoidin.
Goal of the invention
The object of the invention is the new purposes of open jasminoidin.
Jasminoidin is a kind of known material with pharmaceutically active, therefore, can it be prepared into any medicament applicatory clinically according to the formulation method of routine, for example, and tablet, capsule, injection, oral liquid, granule etc.
In the middle of the process of the above-mentioned preparation of preparation, jasminoidin can be used separately, jasminoidin can be mixed use with any excipient that is prepared into clinical medicament that is applicable to, be prepared into pharmaceutical preparation.
The application of jasminoidin in the medicine of preparation antiviral property disease is by following experimental example explanation.
Jasminoidin all has inhibitory action to the inductive cytopathy of influenza, parainfluenza, Coxsackie virus, adenovirus, respiratory syncytial virus, herpesvirus, SARS or bird flu virus, can also suppress duplicating of virus, thereby have treatment viral upper respiratory tract infection and pneumonia, myocarditis, herpes simplex keratitis, the effect of dermopathic herpesvirus disease.
Experimental example 1: jasminoidin extracorporeal antivirus effect experiment
Get the culture plate that grows up to cell monolayer, outwell culture fluid, inoculation 100TCID 50Different virus liquid 50ul, put 37 ℃ of 5% CO 2Absorption was outwelled viral liquid after 1 hour in the incubator, after keeping liquid and wash cell face 2 times with the Eagle ' s that does not contain calf serum, added corresponding dilution medicinal liquid 100ul/ hole.Establish virus control, positive control drug and normal cell contrast simultaneously.Put 37 ℃ of 5% CO 2Cultivate in the incubator, observation of cell pathological changes under the every day inverted microscope, when virus control group cytopathy is ++ ++ the time record experimental result.Cytopathy is judged by six grade standards, and is calculated 50% valid density (EC by Reed-Muench 50) and therapeutic index (TI).
Table 1 jasminoidin is to the TC of Hep-2 cultured cell 0TC 50(mg/ml)
Medicinal liquid Mother liquid concentration TC 0 TC 50
The jasminoidin virazole 100mg/ml 2 3.125 0.5 8.91 0.71
Table 2 jasminoidin extracorporeal antivirus effect experimental unit: mg/ml
Virus is planted Parainfluenza RSV CoxB nacy CoxB 5 HSV-1 HSV-2 A 3 A 7
IC50 TI 1.41 6.32 0.68 13.10 2.23 3.99 2.23 3.99 1.12 7.96 1.07 8.33 6.46 1.38 6.46 1.38
Table 1,2 results show: jasminoidin has obvious inhibitory action at external cytopathogenic effect to parainfluenza virus, RSV, HSV-1, HSV-2, CoxBnacy CoxB5 virus, its IC50 is respectively 1.41,0.68,1.12,1.07,2.23,2.23mg/ml, and TI is respectively 6.32,13.10,7.96,8.33,3.99,3.99; A3, A7 virus are had certain inhibitory action, and IC50 is 6.46,6.46, and TI is 1.38,1.38, so jasminoidin can be used for preparing the application in the medicine for the treatment of viral myocarditis.
Experimental example 2: jasminoidin is to the influence of mice influenza virus property pneumonia
Get 60 of mices, be divided into 6 groups at random by body weight.Be respectively the large, medium and small dosage group of jasminoidin; The virazole matched group; Viral infection matched group and normal control group.Except that the normal control group, mice is slightly anaesthetized with ether, with 15 LD 50Influenza virus drop nose infects, every 0.05ml.Infect and to begin gastric infusion the previous day, every day 2 times, 0.2m/10g, continuous 5 days, matched group under equal conditions distilled water was irritated stomach.Dissected after taking by weighing the mice body weight on the 6th day, win full lung and weigh, calculate the lung exponential quantity, and obtain lung index suppression ratio.
Table 3 jasminoidin is to the influence of mice influenza virus property pneumonia
Group Dosage g/kg/d Mus number (only) Lung exponential quantity (g lung weight/100g body weight) Suppression ratio (%)
Normal control papova matched group virazole group jasminoidin is large, medium and small - - 0.07 1.6 0.8 0.4 10 10 10 10 10 10 0.904±0.008 1.985±0.475## 1.087±0.139** 1.231±0.393** 1.355±0.176** 1.503±0.220* 45.25 37.87 31.81 24.24
Compare with the normal control group: ##P＜0.01
Compare with the virus control group: * P＜0.05
Table 3 result shows: the lung index of three dosed administration groups of jasminoidin mice is significantly less than infection group and viral infection group, with infection group and viral infection group significant difference is arranged relatively, suppression ratio is respectively 37.87%, 31.81%, 24.24%, illustrates that jasminoidin has the obvious suppression effect to mice influenza virus property pneumonia.
Experimental example 3: jasminoidin is to the protective effect of influenza virus induced mice death
Table 4 jasminoidin to influenza virus after the influence of mouse death rate
Group Dosage mg/kg/d Number of animals (only) Death toll Mortality rate % Protective rate %
Dosage group in the heavy dose of group of infection group and viral infection group virazole -- 70 400 200 20 20 20 20 19 8 12 13 95 40 60 65 57.89** 36.84* 31.58*
Compare with matched group: * * P＜0.05 * P＜0.1
Table 4 result shows: in the mouse infection virus 15 days, the dead number average of jasminoidin 400mg/kg/d, 200mg/kg/d dosage treated animal is less than the infection matched group; Dead protective rate is respectively 36.84%, 31.58%, compares with infecting matched group that there were significant differences (P＜0.05), and the expression jasminoidin can obviously reduce mortality of mice behind the influenza infection.
Experimental example 4: the jasminoidin gastric infusion is to the influence of C57 mice herpes simplex keratitis
50 of C57BL/6J mices, male, be divided into 5 groups at random, every group 10, lumbar injection 0.2ml pentobarbital sodium solution (5mg/ml) is anaesthetized, under anatomic microscope, the fine needle head of using the 1ml syringe is at mice one side angle film place standardized gently " ten " word mouth, and every splashes into HSV-1 liquid dilution factor is 10 -1 Viral liquid 5 μ l, massage eyelid gently.Be divided into 5 groups at random: dosage group, administration small dose group in model control group, positive drug control group, the heavy dose of group of administration, the administration.Promptly began administration the same day after planting poison, each medication therapy groups mouse stomach administration, and every day 1 time, each 0.5ml, continuous 21 days, matched group under equal conditions gave aquae destillata.Observed 8 days continuously, cornea every day with fluorescein sodium dyeing after, in slit lamp observation, record pathological changes time of occurrence, cornea epithelial lesion situation, and observe the essence pathological changes is taken pictures under the cobalt blue light source.
The cornea epithelial lesion is divided into the 0-4 degree by accounting for the cornea area: 0 degree: no cornea pathological changes; 1 degree: cornea epithelial lesion scope accounts for below 25% of full-shape film; 2 degree: account for 25% ~ 50%; 3 degree: account for 51 ~ 75%; 4 degree: account for more than 75%.
Count 0.5 degree again with the osf density and the degree of depth between every degree, cornea essence pathological changes is divided into the 0-4 degree: 0 degree: normal; 1 degree: slight edema or slight substrate are opaque; 2 the degree: opaque or substrate edema be limited to corneal diameter 50% in; 3 degree: cornea substrate edema and opaque 50% of the corneal diameter that surpasses; 4 degree: cornea substrate edema and opaque serious, can't see iris.
The average time of occurrence of table 5 keratopathy relatively
Compare * * P＜0.01 with model group
Table 5 result shows: in the jasminoidin, time of occurring of small dose group keratopathy obviously is later than model group, with model group significant difference arranged relatively, illustrates that jasminoidin can obviously suppress the generation of herpes simplex keratitis.
Table 6 corneal epithelium lesion degree
Natural law after the modeling Lesion degree (mean+SD)
Model group The virazole group Heavy dose of group Middle dosage group Small dose group
2 3 4 5 6 7 8 0.85±0.45 1.70±0.46 2.60±0.66 3.10±0.54 3.20±0.60 3.30±0.64 3.35±0.50 0.55±0.47 1.50±0.50 2.40±0.54 2.90±0.66 3.10±0.70 3.10±0.66 3.10±0.70 0.35±0.45* 1.15±0.55* 1.40±0.49** 2.65±0.39 2.70±1.10 2.95±0.96 3.05±0.65 0.30±0.02* 0.90±0.49** 1.25±0.46** 2.35±0.59* 2.60±0.77 2.90±0.89 2.90±1.04 0.46±0.02* 0.95±0.52** 1.30±0.50** 2.60±0.49 3.00±0.50 3.25±0.68 3.15±0.71
Compare * P＜0.05, * * P＜0.01 with model group
Table 7 cornea essence lesion degree
Natural law after the modeling Lesion degree (mean+SD)
Model group The virazole group Heavy dose of group Middle dosage group Small dose group
2 3 4 5 6 7 8 0 0.55±0.57 1.15±0.85 2.35±0.67 2.65±0.67 2.75±0.71 3.10±0.52 0 0.50±0.55 0.90±0.44 1.90±0.84 2.60±0.66 2.65±0.41 2.95±0.72 0 0.30±0.46 0.80±0.67 1.44±0.85* 1.80±0.86* 2.30±1.27 2.45±1.30 0 0.10±0.20* 0.75±0.63* 1.45±0.83* 1.95±0.80* 2.20±0.92 2.45±1.12 0 0.20±0.33* 0.75±0.60* 1.30±0.82* 2.10±1.16* 2.70±1.25 2.75±1.09
Compare * P＜0.05 with model group
Table 6,7 results show: the epithelial lesion and the cornea essence pathological changes of three dosed administration treated animals of jasminoidin cornea obviously alleviate than model group, especially with model group significant difference is arranged relatively within one week of modeling, illustrate that jasminoidin has the obvious treatment effect to the mice herpes simplex keratitis.
Experimental example 5: to the death protection of C57 mouse herpesvirus encephalitis model
Above-mentioned 50 C57 mices were observed 21 continuously, write down in 21 days and respectively organize dead mouse date and death toll, calculate mean survival time, dead protective rate and increase in life span, the result adopts X 2 test and T check to carry out statistical procedures.
The death protection of table 8 pair C57 mouse herpesvirus encephalitis model
Compare * P＜0.05 * * P＜0.01 with model group
Table 8 result shows: the mortality rate of three dosed administration treated animals of jasminoidin is starkly lower than model group, and obviously prolongs life cycle, illustrates that jasminoidin has significant protective effect to the death of mouse herpesvirus encephalitis.
Experimental example 6: jasminoidin and pastille serum are in the external influence that herpes virus DNA is duplicated
Jasminoidin is irritated stomach and is given rat, for three days on end, gathers serum, and the method for exempting from external employing side is measured the influence to viral dna replication, and the result is as follows:
The influence that table 9 pair herpes virus DNA duplicates
Group The CPM value Suppression ratio
Virus control group jasminoidin group normal serum group pastille serum group 14919.67±1984.16 12742.33±3051.47** 15896.30±538.11 13449.07±712.57## 14.52 15.39
* and matched group be P＜0.05 relatively
## and normal serum group be P＜0.05 relatively
The result shows in the table: jasminoidin and pastille serum thereof all have the obvious suppression effect to the dna replication dna of herpesvirus.Jasminoidin can be used for preparing the application in the medicine for the treatment of dermopathic herpesvirus disease.
Fig. 1 inoculates back the 5th day, and with slit lamp examination C57BL/6J mice cornea, the model control group cornea is impaired serious, and major part ulceration;
Fig. 2 inoculates back the 5th day, and with slit lamp examination C57BL/6J mice cornea, positive controls corneal infiltration scope reaches more than 3/4, presents the map shape;
Fig. 3 inoculates back the 5th day, and with slit lamp examination C57BL/6J mice cornea, administration group (0.8g/kg/ days) cornea piece occurs soaking into and is linked to be strip;
Fig. 4 inoculates back the 5th day, and with slit lamp examination C57BL/6J mice cornea, administration (0.4g/kg/ days) corneal infiltration scope does not reach 1/2, and little bulk;
Fig. 5 corneal epithelium lesion degree change curve;
Fig. 6 cornea essence lesion degree change curve.
Embodiment 1:
Jasminoidin raw material 0.15g, medical starch 0.15g, mix homogeneously is used an amount of alcohol granulation, through the pelletizing machine granulate, tabletting, every 0.3g, the viral respiratory tract infection patient is oral, and each 2, every day 2 times.
Embodiment 2:
Jasminoidin raw material 0.15g, medical starch 0.15g, mix homogeneously is used an amount of alcohol granulation, through the pelletizing machine granulate, tabletting, every 0.3g, viral respiratory tract infection and pneumonia patient are oral, and each 2, every day 2 times.
Embodiment 3:
Jasminoidin raw material 0.15g, medical starch 0.15g, mix homogeneously is used an amount of alcohol granulation, through the pelletizing machine granulate, tabletting, every 0.3g, the dermopathic herpesvirus disease patient is oral, and each 2, every day 2 times.
Embodiment 4:
Jasminoidin raw material 0.15g, medical starch 0.15g, mix homogeneously, the 1# capsule of packing into gets capsule, every 0.3g, the herpes viral encephalitis patient is oral, and each 2, every day 3 times.
Embodiment 5:
Jasminoidin raw material 0.15g, medical starch 0.15g, mix homogeneously, the 1# capsule of packing into gets capsule, every 0.3g, the herpes simplex keratitis patient is oral, and each 2, every day 3 times.
Embodiment 6:
The jasminoidin raw material is made injectable powder, every bottle of 2g, viral disease patient's dead point, per 60 kg body weight 4g, every day 2 times.

Claims (7)

1, the application of jasminoidin in the medicine of preparation treatment influenza virus, parainfluenza virus, Coxsackie virus, adenovirus, respiratory syncytial virus or herpes simplex virus disease.
2, the application of jasminoidin in the medicine of preparation treatment influenza virus property pneumonia.
3, the application of jasminoidin in the medicine of preparation treatment viral myocarditis.
4, the application of jasminoidin in the medicine of preparation treatment herpes simplex keratitis.
5, the application of jasminoidin as claimed in claim 4 is characterized in that described treatment herpes simplex keratitis is meant inhibition cornea epithelial lesion and cornea essence pathological changes.
6, the application of jasminoidin in the medicine of preparation treatment dermopathic herpesvirus disease.
7, the application of jasminoidin in the medicine of preparation treatment herpes viral encephalitis.
CNB2004100340387A 2004-04-22 2004-04-22 Novel usage of jasminoidin Expired - Fee Related CN1299692C (en)

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CN102784167B (en) * 2011-05-20 2014-10-29 上海凯宝药业股份有限公司 Pharmaceutical composition for treating viral pneumonia
CN103372078A (en) * 2012-04-19 2013-10-30 中国中医科学院中药研究所 Medicine for treating influenza and preparation method thereof
CN106511329A (en) * 2016-12-07 2017-03-22 徐州诺克非医药科技有限公司 Pharmaceutical composition containing Euphorbactin and application of pharmaceutical composition

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CN1460483A (en) * 2003-06-10 2003-12-10 北京正青星光生物医学科技有限公司 Medicine for curing cerebrovascular diseases and its preparation method

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1460483A (en) * 2003-06-10 2003-12-10 北京正青星光生物医学科技有限公司 Medicine for curing cerebrovascular diseases and its preparation method

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