CN1481893A - Novel use of boninmycin in curing disease resulted from papillomavirus - Google Patents
Novel use of boninmycin in curing disease resulted from papillomavirus Download PDFInfo
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- CN1481893A CN1481893A CNA031413757A CN03141375A CN1481893A CN 1481893 A CN1481893 A CN 1481893A CN A031413757 A CNA031413757 A CN A031413757A CN 03141375 A CN03141375 A CN 03141375A CN 1481893 A CN1481893 A CN 1481893A
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- papillomavirus
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Abstract
The present invention relates to the new application of Boningmycen as one new antitumor antibiotic in treating diseases caused by papillomavirus. The said diseases are skin tumor wart of daily cow and other animal as well as human body, and there is effective treatment measures available. The present invention prepares Boningmycen as one new antitumor antibiotic into required preparation form, such as cream, for treating diseases caused by papillomavirus and obtains obvious curative effect, low toxicity, no irritation to skin and other negative reaction. Therefore, Boningmycen is expected to become the medicine for treating diseases caused by papillomavirus.
Description
Technical field:
The present invention relates to a kind of new new purposes of antitumor antibiotics in treatment human papillomavirus associated diseases.
Background technology:
The swollen wart of skin that is caused by human papillomavirus (Papilloma virus) abbreviates wart (Warts) as.This virus extensively is present in the natural environment, and is strong to the resistance of various physics, chemical factor.The genome of virus is bifilar cyclic DNA.On the one hand, this disease is common in milk cattle, and its sickness rate can reach more than 30%, even can be up to 59%.Grow in the tumor body of cow teats skin, can be different shape, as Herba pteridii latiusculi shape, finger-like, flat etc.Suffer from this sick milk cattle, influence milk matter even become the immediate cause that milk cattle is eliminated owing to containing this virus in the milk.On the other hand, human papillomavirus (HPV) can cause verruca vulgaris, condyloma acuminatum (claiming genital wart or genital wart again), verruca vulgaris and verruca plana etc.The sickness rate of condyloma acuminatum rises day by day in many countries and regions, has become the modal a kind of viral sexually transmitted disease (STD) of developed country now.In China, its sickness rate has accounted for second of spread of sexually transmitted diseases disease.Think that at present the source of infection of condyloma acuminatum is not only the patient, the equal tool infectiousness of virus carrier and subclinical infection person.Traditional physical property treatment and laser, means such as freezing be owing to can not eliminate subclinical infection, more after very easily recurrence, treat very thorny.The formation evidence relevant with HPV of many neoplasmata genitalises also found in research.Be used for the treatment of the medicine of condyloma acuminatum such as sufficient leaf poison glycoside etc. at present, because of toxic and side effects is bigger, influenced therapeutic effect, particularly zest is difficult to acceptance for the patient by force.At this sick vaccine, loaded down with trivial details because of seedling, duration of immunity is short, and protective rate is low also to be applied.The formation evidence relevant with HPV of many neoplasmata genitalises also found in research.So it is very necessary to seek a kind of medicine evident in efficacy, treatment papillomatosis that toxic and side effects is little.This reality chamber of grinding studies show that before this, Z-893 Boningmycin (also claiming Z-893) has good antineoplastic activity, particularly effect and the B1eomycin to zoografting hepatocarcinoma is suitable, but its acute toxicity is lower one times than B1eomycin, especially its lung toxicity is extremely low, the research achievement has been applied for Chinese patent [Gazette of Patent for Invention, 15 (41), publication number: CN1231340A].Inventor's research subsequently proves that further the various warts that Z-893 Boningmycin causes human papillomavirus swell and also demonstrate good effect, provide foundation for its exploitation being become a kind of active drug for the treatment of the human papillomavirus associated diseases.Z-893 Boningmycin used in the present invention (Boningmycin) is a kind of new glycopeptide antibiotics, belongs to bleomycin (Bleomycin) family medicine, and its chemical constitution is as follows:
R＝NH(CH
2)
3NH(CH
2)
4NH(CH
2)
3NHCOCH
3
MW：1540(M+1，FAB-MS)C
62H
98N
20O
22S
2
Z-893 Boningmycin is to separate a noval chemical compound that obtains from bleomycin A5 (bleomycin) complex.Bleomycin A5 is by streptomyces verticillatus Pingyang mutation (Streptomyces verticillus var.pingyangensis n.sp) [microorganism journal, 1979; 19 (4): 361-364] one group of complex of Chan Shenging with anti-tumor activity.Z-893 Boningmycin can be obtained through submerged fermentation cultivation, separation and Extraction by the mutation of streptomyces verticillatus Pingyang.
The object of the present invention is to provide a kind of Z-893 Boningmycin treating the particularly new purposes in treatment condyloma acuminatum, verruca vulgaris and flat Verrucosis of human papillomavirus associated diseases.
Summary of the invention:
The biological test of Z-893 Boningmycin:
The medicine that the present invention is used for the treatment of the human papillomavirus associated diseases is a Z-893 Boningmycin, and its dosage form can be the Z-893 Boningmycin cream, also can be ointment, gel, liniment or injection etc.Said dosage form can preparation method routinely obtain.
1, safety testing
Animal: Beijing Black is spent 1 of milk cattle bull calf, 7 ages in days in vain.
Medicine: 0.5% Z-893 Boningmycin cream compares with cream base.
Method: on the hind leg inside skin of the selected bull calf left and right sides, choose 3 * 3cm respectively
2Each one of area, wherein left hind is coated with the Z-893 Boningmycin cream, and the right hind corresponding site is coated with the substrate of Z-893 Boningmycin cream, in contrast.Morning and afternoon every day, each coating was 1 time, carried out continuously 7 days.
Observe: twice of every day (morning 8:30, afternoon 15:30), viewing test cattle agents area skin had or not red, swollen, hot, bitterly and the malfunction variation; Have or not pathological changes such as foaming, ulceration, necrosis, incrustation, to judge the biological safety of said medicine to test Corii Bovis seu Bubali skin.
Result: by test in 7 days,, also do not bubble, pathological changes such as ulcer, with coating position skin is not as broad as long no matter color change does not all take place for the left hind thigh inboard contrast skin or the skin of right hind corresponding site.In experimental period, tried that calf searches for food, drinking-water, body temperature, breathing and the mental status be all normal.Illustrate that the clinical use of Z-893 Boningmycin cream is safe.
2, pharmacodynamics test
Animal: clinical ill cattle is divided into two groups immediately, and 6 every group, wherein one group as experimental group, and another group is group in contrast, has the tumor body of two milk cattle to be finger-like in the experimental group, and the tumor body of all the other cases all is flat.
Medicine: 0.5% Z-893 Boningmycin cream, cream base in contrast.
Method: the milk cattle of natural occurrence in the cows is accessed from former colony, concentrate and raise, make experimental group and matched group term harmonization, i.e. the quantity of feeding environment, feeding manner, raising, raising and quality basically identical.After milking, immediately medicine and substrate are applied on the tumor of experiment cattle and contrast cow teats skin at every turn, carried out continuously 10 days.
Observe: add up day by day, write down and tried cattle and the contrast cattle disease becomes situation such as tumorigenic position, tumor body size variation (with the diameter of the maximum tumor body of slide calliper rule amount), shape, color, has or not the sign that comes off etc. (table 1).
The effect of table 1 0.5% Z-893 Boningmycin cream treatment mammilla of milk cattle shape tumor
Experimental group matched group cattle date tumor body
*Shape is degraded the cattle date tumor body that comes off
*Shape is degraded and is come off
Preceding 3.2 finger-like of preceding 4.1 finger-like--96022 experiment of size (mn) size (mn) 95261 experiments--
Come off after the experiment-+preceding 3.8 finger-like--96162 of experiment back 3.2 finger-like--95034 experiment test preceding 3.5 flat--
Come off after the experiment-+3.5 flat--96072 experiments preceding 6.3 flat--96028 of experiment back test preceding 2.7 flat--
Experiment back is 6.1 flat+-2.8 flat--96306 experiments preceding 3.6 flat--95274 of experiment back test preceding 4.3 flat--
Experiment back is 3.6 flat+-4.3 flat--96047 experiments preceding 4.4 flat--96061 of experiment back test preceding 3.1 flat--
Experiment back is 4.3 flat+-3.0 flat--96059 experiments preceding 0.2 flat--1515 of experiment back test preceding 8.7 flat--
0.2 is flat after the experiment+-8.8 is flat after testing--
*Refer to maximum tumor body base diameter
Experimental result shows that 0.5% Z-893 Boningmycin cream has the good curing effect to papilloma.In 10 days the course of treatment, two routine finger-like papillary tumor came off respectively at the 6th day and the 9th day, though the little wrinkle of place's skin that comes off does not have obvious boundary with surrounding skin, no cicatrization.Do not have obviously difference when the finger-like tumor experiment of matched group finishes with before the experiment, do not have obscission.
Because it is harder that flat tumor is the keratinization state surface, though the Z-893 Boningmycin cream fails to make it to come off, do not cause that the tumor body dwindles (tumor body base diameter does not have significant change) yet, but the tumor surface of all experimental grouies all takes place significantly to degrade, show as that the tumor surface is coarse, decortication, outward appearance be and degrade shape, the tumor body is obviously dwindled in the projection degree of skin surface, and the height of tumor descends.Above phenomenon, performance at experimental group 4 cow heads is consistent, the phenomenon and the flat tumor body of 5 cow heads of matched group does not all degrade, peels, and the height of indivedual tumor bodies increases before the experiment, explanation, 0.5% Z-893 Boningmycin cream can cause that flat is papillomatous and degrade, peels, can suppress its growth.
The invention effect:
The invention has the advantages that employed medicine Z-893 Boningmycin has very hypotoxicity, especially lung toxicity is extremely low, and the important feature of tool antivirus action, but both systemic administrations, but also local topical.Swollen wart due to the external-application cream treatment human papillomavirus, evident in efficacy, no local irritant effect has overcome the clinical antineoplastic agent of similar disease or the defective that special medicine exists of being used for the treatment of, and has a good application prospect.
Claims (3)
1, the application of Z-893 Boningmycin in preparation treatment human papillomavirus associated diseases medicine.
2, application as claimed in claim 1 is characterized in that referring to the application in preparation treatment condyloma acuminatum, verruca plana and verruca vulgaris medicine.
3, application as claimed in claim 1 or 2 is characterized in that the preferably application in preparation treatment condyloma acuminatum medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031413757A CN1481893A (en) | 2003-06-06 | 2003-06-06 | Novel use of boninmycin in curing disease resulted from papillomavirus |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031413757A CN1481893A (en) | 2003-06-06 | 2003-06-06 | Novel use of boninmycin in curing disease resulted from papillomavirus |
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| Publication Number | Publication Date |
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| CN1481893A true CN1481893A (en) | 2004-03-17 |
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| CNA031413757A Pending CN1481893A (en) | 2003-06-06 | 2003-06-06 | Novel use of boninmycin in curing disease resulted from papillomavirus |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112472793A (en) * | 2020-12-07 | 2021-03-12 | 中国医学科学院医药生物技术研究所 | Application of boningmycin in inhibiting PD-L1 high-expression tumor |
-
2003
- 2003-06-06 CN CNA031413757A patent/CN1481893A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112472793A (en) * | 2020-12-07 | 2021-03-12 | 中国医学科学院医药生物技术研究所 | Application of boningmycin in inhibiting PD-L1 high-expression tumor |
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