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CN105055401A - Application of chrysin in preparing cryptosporidium parvum resisting medicine - Google Patents

Application of chrysin in preparing cryptosporidium parvum resisting medicine Download PDF

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Publication number
CN105055401A
CN105055401A CN201510512866.5A CN201510512866A CN105055401A CN 105055401 A CN105055401 A CN 105055401A CN 201510512866 A CN201510512866 A CN 201510512866A CN 105055401 A CN105055401 A CN 105055401A
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CN
China
Prior art keywords
chrysin
alkyl
independent
cryptosporidium parvum
application
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Pending
Application number
CN201510512866.5A
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Chinese (zh)
Inventor
向蓉
李娟�
孙铭飞
林栩慧
吕敏娜
廖申权
戚南山
吴彩艳
吴丹凤
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Institute of Animal Health of Guangdong Academy of Agricultural Sciences
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Institute of Animal Health of Guangdong Academy of Agricultural Sciences
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Application filed by Institute of Animal Health of Guangdong Academy of Agricultural Sciences filed Critical Institute of Animal Health of Guangdong Academy of Agricultural Sciences
Priority to CN201510512866.5A priority Critical patent/CN105055401A/en
Publication of CN105055401A publication Critical patent/CN105055401A/en
Pending legal-status Critical Current

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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses chrysin and application of medicinal derivatives of the chrysin in preparing cryptosporidium parvum resisting medicine or feed additives. The chrysin and the medicinal derivatives of the chrysin have excellent cryptosporidium parvum resisting activity, an animal infection experiment proves that the ovulation quantity of cryptosporidium parvum can be reduced by more than 70% by adding the chrysin, and the chrysin has an excellent cryptosporidium parvum resisting effect and is expected to be developed into the cryptosporidium parvum resisting medicine or feed additives. In addition, the chrysin is easy to prepare and low in extraction cost and can be easily developed into the low-cost cryptosporidium parvum resisting medicine or feed additives.

Description

The application of chrysin in the anti-Cryptosporidum parvum medicine of preparation
Technical field
The present invention relates to the new opplication of a compounds, the particularly application of chrysin in the anti-Cryptosporidum parvum medicine of preparation.
Background technology
Cryptosporidium (Cryptosporidium) is in worldwide distribution.Infect people and most of mammiferous be Cryptosporidum parvum ( cryptosporidiumparvum).Cryptosporidium is a kind of important Opportunistic protozoa causing humans and animals to suffer from diarrhoea.Severe infections person, intestinal villi surface can occur depression, atrophy, shorten thicker, or merge, be shifted and come off; Disorder of Digestion and Absorption and diarrhoea can be caused.
After the normal person of immunologic function infects this worm, normal table self limiting diarrhoea, feces be water sample, and amount is large, can have abdominal cramps pain, the symptoms such as nauseating, anorexia, heating and general malaise.The patient of immunologic dysfunction, the outbreak of disease mostly is gradual, but the degree of diarrhoea is often even more serious, and feces amount can reach 5-10L.If the immunodeficiency conditions of patient can not get correcting, infect and just can not remove.Even diarrhoea can continue for a long time throughout one's life.Then cause nutrient malabsorption, even occur the outer histoorgan of intestinal, as lungs and biliary system infect.Cryptosporidium is the common causative that aids patient merges intestinal infection, usually jeopardizes the life of patient after infection.
At present, the treatment for primary disease there is no desirable active drug.Bibliographical information garlicin, paromomycin are treated, and have certain curative effect.
Chrysin (chemistry is by name: chrisin, 5,7-dihydroxy-2-phenyl-4H-chromen-4-one), the molecular formula of this compound is C 15h 10o 4, molecular weight 254, CAS accession number: 480-40-0, its chemical constitution is such as formula shown in lower:
Chrysin be present in Bignoniaceae plant oroxylum indicum [ oroxylumindicum(L.) Vent.] seed, peel of stem, pinaceae plant western white pine (PinusmonicolaDougl.) the heart wood, bristlecone pine ( p.aristataEngelm.) the heart wood etc.
Chrysin has the effects such as anticancer, blood fat reducing, anti-cardiovascular and cerebrovascular disease, antibacterial, antiinflammatory.
At present, chrysin is not had to have the report of anti-Cryptosporidum parvum effect.
Summary of the invention
The object of the present invention is to provide chrysin and the application of medicinal derivative in the anti-Cryptosporidum parvum medicine of preparation thereof.
Another object of the present invention is to provide chrysin and medicinal derivative thereof preparing the application in feed additive.
The technical solution used in the present invention is:
Chrysin and the application of medicinal derivative in the anti-Cryptosporidum parvum medicine of preparation thereof.
Further, the structural formula of above-mentioned chrysin medicinal derivative is:
, wherein M 1and M 2it is independently the ion of IA race, IIA race element;
Or be , wherein R 1and R 2independent is C 1~ C 10alkyl;
Or be wherein R 3and R 4independent is C 1~ C 10alkyl.
Further, above-mentioned M 1and M 2independent is Li +, Na +, K +, Mg 2+, Ca 2+in one; Described R 1, R 2, R 3and R 4independent is C 1~ C 5alkyl.
Further, above-mentioned R 1, R 2, R 3and R 4for alkyl.
Further, said medicine dosage form is oral formulations.
Chrysin and medicinal derivative thereof are preparing the application in feed additive.
Further, above-mentioned chrysin medicinal derivative is: , wherein M 1and M 2it is independently the ion of IA race, IIA race element;
Or be: , wherein R 1and R 2independent is C 1~ C 10alkyl;
Or be: wherein R 3and R 4independent is C 1~ C 10alkyl.
Further, above-mentioned M 1and M 2independent is Li +, Na +, K +, Mg 2+, Ca 2+in one; Described R 1, R 2, R 3and R 4independent is C 1~ C 5alkyl.
Further, above-mentioned R 1, R 2, R 3and R 4for alkyl.
The invention has the beneficial effects as follows:
Inventor, by by chrysin and acceptable adjuvant, makes powder, is added in feedstuff, mixing, and by daily forage volume feeding white mice, the addition of chrysin is add 5g chrysin in every 100kg feedstuff; Or chrysin is made chrysin water solube powder, soluble in water, by everyday water-drinking amount feeding white mice, the addition of chrysin is be dissolved in 2.5g chrysin in every 100kg water.Confirm that adding chrysin can make anti-Cryptosporidum parvum ovulation capsule amount reduce by more than 70%, has good anti-Cryptosporidium effect by zoogenetic infection experiment.Meanwhile, chrysin is easy to preparation, and extraction cost is relatively low, is easy to the anti-Cryptosporidum parvum medicine or the feed additive that are developed as low cost.
Detailed description of the invention
Chrysin and derivant thereof are in the application preparing anti-Cryptosporidum parvum medicine or prepare in feed additive, and the structural formula of chrysin is:
The dosage form of medicine or feed additive is oral formulations.
Preferential, the structural formula of above-mentioned chrysin medicinal derivative is:
, wherein M 1and M 2it is independently the ion of IA race, IIA race element;
Or be: , wherein R 1and R 2independent is C 1~ C 10alkyl;
Or be: wherein R 3and R 4independent is C 1~ C 10alkyl.
Preferred, above-mentioned M 1and M 2independent is Li +, Na +, K +, Mg 2+, Ca 2+in one; Described R 1, R 2, R 3and R 4independent is C 1~ C 5alkyl.
Most preferred, above-mentioned R 1, R 2, R 3and R 4for alkyl.
Below in conjunction with specific embodiment, this explanation is further described, but does not limit to so.
embodiment 1
The preparation of chrysin powder: get 5g chrysin (content is not less than 99%) and the mixing of 95g starch.
The usage and dosage of powder: admix in 100kg feedstuff by above-mentioned 100g powder, by daily appetite feeding.
embodiment 2
The preparation of chrysin water solube powder: get 2.5g chrysin (content is not less than 99%) and the mixing of 97.5g glucose.
The usage and dosage of water solube powder: be dissolved in 100 premium on currency by above-mentioned 100g powder, by normal water amount feeding.
embodiment 3
The preparation of chrysin medicinal derivative water solube powder: get 2.5g chrysin medicinal derivative (content is not less than 99%) and the mixing of 97.5g glucose.
The usage and dosage of water solube powder: be dissolved in 100 premium on currency by above-mentioned 100g powder, by normal water amount feeding.
Be representative below with chrysin, in conjunction with the effect of concrete description of test chrysin and the anti-Cryptosporidum parvum of medicinal derivative thereof.
experiment material:
Control drug: the paromomycin (98%, Shanghai Fu Sheng Bioisystech Co., Ltd, lot number 001010) with anti-Cryptosporidum parvum effect of bibliographical information, use amount is 5mg/kg body weight.
Chrysin: the chrysin powder of embodiment 1, the chrysin water solube powder of embodiment 2.
Cryptosporidium parvum Oocysts: Cryptosporidum parvum ( cryptosporidiumparvum) Guangdong Strain egg capsule, preserved by Institute of Animal Health,Guangdong Academy Of Agricultural Sciences, rejuvenation in SPF level Kunming mouse body before using.
Mice: SPF level Kunming mouse, 6 week age, male; Thered is provided by Nanfang Medical Univ's Experimental Animal Center, raise in SPF animal house; Free choice feeding and drinking pure water; Observe mice before test and check that feces is with or without Cryptosporidium parvum oocysts suspended with or without cryptosporidiosis clinical symptoms and continuous 2d, for subsequent use.
Feedstuff: provided by Nanfang Medical Univ's Experimental Animal Center.
experimental technique:
Grouping: by test grouping and process by 50 SPF level Kunming mouses, be divided into 5 groups at random, often organize 10, and suitably adjustment to make often to organize mice TBW roughly equal.
Process: except I (blank) group, all the other respectively organize mice equal administered by oral gavage Cryptosporidium parvum Oocysts l × 10 5individual/only; Except Group I and the IIth (positive control) group, all the other respectively group mices all feed immediately after infecting or the feedstuff drunk containing anti-Cryptosporidium medicine or water, feed containing the feedstuff of paromomycin for IIIth group, the chrysin spice that the chrysin powder of the IVth group of embodiment 1 of feeding and feedstuff are made, the Vth group of chrysin water solube powder drinking embodiment 2 is drunk water with the chrysin made of drinking water, and each group drinking-water is all identical with the consumption of feedstuff.The grouping situation of test mice is in table 1.
Table 1 test mice divides into groups
Observe every day and record the mental status, feces situation etc. of mice; To dead mouse weights, cut open inspection.
Egg capsule slip after drug effect decision method Main Basis infects; Carry out as follows: after infecting the 3rd day starts to collect feces every day, continuously monitoring 15 days.Get feces every day to eluriate, 260 mesh screen, filtrate, through the centrifugal 10min of 3000r/min, is abandoned and is reset and added the saturated sucrose solution of 15mL, shake up, the centrifugal 10min of 1200/min; Carefully pick supernatant 20uL after centrifugal immediately on red blood cell count(RBC) plate, microscope (10 × 40 times) is observed egg capsule and is counted.
experimental result:
Clinicing symptom observation:
The matched group of inoculation Cryptosporidium parvum Oocysts the 3rd day, mice occurs that spirit is depressed, and by hair slightly disorderly, within the 4th day, play symptom of diarrhea obvious, period has no dead mouse.
Calculate on average every mice row's egg sac number and the egg capsule slip of each group respectively, the results are shown in Table shown in 2.
Table 2 is the anti-Cryptosporidium effect of group respectively
As shown in Table 2, III, on average every mice row egg sac number of IV, V group is all lower than the IIth group, IV, on average every mice row egg sac number of V group is starkly lower than the IIIth group, historical facts or anecdotes verifies that real chrysin can make the metainfective egg sac number of Cryptosporidum parvum reduce more than 89%, drinking-water group effect is better than feedstuff interpolation group, there is good anti-Cryptosporidum parvum effect, and be obviously better than paromomycin.
Above-mentioned experimental result illustrates, chrysin has the effect of anti-Cryptosporidum parvum; By chrysin and acceptable adjuvant, powder can be made, as feed additive; Or chrysin is made chrysin water solube powder, and soluble in water, by everyday water-drinking amount feeding animals.
Above-described embodiment is the present invention's preferably embodiment; but embodiments of the present invention are not restricted to the described embodiments; change, the modification done under other any does not deviate from spirit of the present invention and principle, substitute, combine, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.

Claims (9)

1. chrysin and the application of medicinal derivative in the anti-Cryptosporidum parvum medicine of preparation thereof.
2. application according to claim 1, is characterized in that: the structural formula of described chrysin medicinal derivative is:
, wherein M 1and M 2it is independently the ion of IA race, IIA race element;
Or be: , wherein R 1and R 2independent is C 1~ C 10alkyl;
Or be: wherein R 3and R 4independent is C 1~ C 10alkyl.
3. apply according to claim 2, it is characterized in that: described M 1and M 2independent is Li +, Na +, K +, Mg 2+, Ca 2+in one; Described R 1, R 2, R 3and R 4independent is C 1~ C 5alkyl.
4. apply according to claim 3, it is characterized in that: described R 1, R 2, R 3and R 4for alkyl.
5. apply according to claim 1, it is characterized in that: described pharmaceutical dosage form is oral formulations.
6. chrysin and medicinal derivative thereof are preparing the application in feed additive.
7. application according to claim 6, is characterized in that: described chrysin medicinal derivative is: , wherein M 1and M 2it is independently the ion of IA race, IIA race element;
Or be: , wherein R 1and R 2independent is C 1~ C 10alkyl;
Or be: wherein R 3and R 4independent is C 1~ C 10alkyl.
8. apply according to claim 7, it is characterized in that: described M 1and M 2independent is Li +, Na +, K +, Mg 2+, Ca 2+in one; Described R 1, R 2, R 3and R 4independent is C 1~ C 5alkyl.
9. apply according to claim 8, it is characterized in that: described R 1, R 2, R 3and R 4for alkyl.
CN201510512866.5A 2015-08-20 2015-08-20 Application of chrysin in preparing cryptosporidium parvum resisting medicine Pending CN105055401A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108125975A (en) * 2018-01-29 2018-06-08 广东省农业科学院动物卫生研究所 Application of the Rhoifolin in anti-Cryptosporidum parvum drug is prepared
CN108478587A (en) * 2018-04-08 2018-09-04 广州市汇鑫动物药业有限公司 Application of the scutelloside in preparing anti-Cryptosporidium baileyi drug

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009052411A2 (en) * 2007-10-19 2009-04-23 National Jewish Medical And Research Center Methods for treatment of thiol-containing compound deficient conditions
CN104012779A (en) * 2014-06-25 2014-09-03 无锡市朗邦生物科技有限公司 Preparation method and application of immune preparation capable of enhancing immunities of fishes, prawns and crabs
CN104688726A (en) * 2015-02-04 2015-06-10 郑州点石生物技术有限公司 Application of isoflavone compounds in preparation of anti-cryptosporidium-parvum medicines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009052411A2 (en) * 2007-10-19 2009-04-23 National Jewish Medical And Research Center Methods for treatment of thiol-containing compound deficient conditions
CN104012779A (en) * 2014-06-25 2014-09-03 无锡市朗邦生物科技有限公司 Preparation method and application of immune preparation capable of enhancing immunities of fishes, prawns and crabs
CN104688726A (en) * 2015-02-04 2015-06-10 郑州点石生物技术有限公司 Application of isoflavone compounds in preparation of anti-cryptosporidium-parvum medicines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
王秋亚等: "白杨素衍生物的合成及生理活性研究进展", 《化学研究》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108125975A (en) * 2018-01-29 2018-06-08 广东省农业科学院动物卫生研究所 Application of the Rhoifolin in anti-Cryptosporidum parvum drug is prepared
CN108478587A (en) * 2018-04-08 2018-09-04 广州市汇鑫动物药业有限公司 Application of the scutelloside in preparing anti-Cryptosporidium baileyi drug

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Application publication date: 20151118