CN105560257A - Novel drug for treating bacterial infection - Google Patents

Novel drug for treating bacterial infection Download PDF

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Publication number
CN105560257A
CN105560257A CN201610002241.9A CN201610002241A CN105560257A CN 105560257 A CN105560257 A CN 105560257A CN 201610002241 A CN201610002241 A CN 201610002241A CN 105560257 A CN105560257 A CN 105560257A
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CN
China
Prior art keywords
medicine
younghusbandii
incarvillea
compd
purposes
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CN201610002241.9A
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Chinese (zh)
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李春华
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Individual
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Priority to CN201610002241.9A priority Critical patent/CN105560257A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1652Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • 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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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to a novel drug for treating bacterial infection. The invention provides a drug containing an incarvillea younghusbandii phenylpropanoid glycoside compound (A). The drug is used to treat bacterial infection, the bacteria comprise escherichia coli, staphylococcus aureus, candida albicans, and pseudomonas aeruginosa, and the drug can also be used to treat dermatitis.

Description

The newtype drug for the treatment of bacteriological infection
Technical field
The present invention relates to medicinal chemistry arts, particularly, relate to the purposes of Incarvillea younghusbandii phenylpropanoid glycoside A in treatment bacteriological infection.
Background technology
Hide POLO Hua Shi China distinctive species in Qinghai-Tibet Platean, be born in alpine scrub meadow or the alpine meadow of height above sea level 3600-5400 rice.Known Tibetan POLO flower having enrich blood foster the spirit of nobility, the effect such as expelling wind and removing dampness.From Tibetan POLO is spent, isolate Incarvillea younghusbandii phenylpropanoid glycoside compound, comprise Incarvillea younghusbandii phenylpropanoid glycoside compd A and Incarvillea younghusbandii phenylpropanoid glycoside compd B.Existing scientific achievement shows that Incarvillea younghusbandii phenylpropanoid glycoside compound has the effect such as antioxidation, treatment atherosclerosis.CN101264094A(application number 200810044220.9) describe extracting method and the structural formula of Incarvillea younghusbandii phenylpropanoid glycoside compound, the document quotes in full the part as present specification at this.
Present invention applicant, by studying for many years, finds that Incarvillea younghusbandii phenylpropanoid glycoside compd A has good bacterial-infection resisting and anti-dermatitis is active.
Summary of the invention
One aspect of the present invention, provides a kind of medicine, comprising Incarvillea younghusbandii phenylpropanoid glycoside compd A.
Another aspect of the present invention, provides the purposes of Incarvillea younghusbandii phenylpropanoid glycoside compd A in the medicine of preparation treatment bacteriological infection.
Another aspect of the present invention, described antibacterial comprises escherichia coli, staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa.
Another aspect of the present invention, provides the purposes of Incarvillea younghusbandii phenylpropanoid glycoside compd A in the medicine of preparation treatment dermatitis.
Another aspect of the present invention, meets subject patient and comprises mammal and birds.
Another aspect of the present invention, meeting subject patient is people.
Medicine of the present invention can be any medicine type known in the art, includes but not limited to tablet, capsule, drop pill, injection, freeze-dried powder, decoction, slow releasing preparation, powder, granule, suppository, aerosol etc.
Useful in preparing drug formulations of the present invention adopts excipient substance known in the art, comprises binding agent, filler, lubricant, diluent, solvent, slow-release material etc.Include but not limited to starch, dextrin, lactose, mannitol, microcrystalline Cellulose, hypromellose, polyvidone, cross-linking sodium carboxymethyl cellulose, Pulvis Talci, stearic acid, poloxamer, ethyl cellulose, acrylic resin etc.
Medicine of the present invention can be used by topical and systemic administration.Local administration comprises topical.Systemic administration comprises oral, parenteral (such as intravenous, intramuscular, subcutaneous or rectum), and other system route of administration.In systemic administration, first this reactive compound arrives blood plasma, is then distributed in target tissue.Topical and oral administration are route of administration preferred for the present invention.
Following examples set forth the present invention further.These embodiments are only intended to the present invention is described, and should not be understood to restricted.
Detailed description of the invention
Embodiment 1:
Get Incarvillea younghusbandii phenylpropanoid glycoside compd A 100g, add starch dust 160g, with the mixing of equal increments method, with the ethanol of 80%, make granule, dry, granulate, mixing, add Pulvis Talci 4g, magnesium stearate 1.6g, namely tabletting obtains (1000).
Embodiment 2:
Get Incarvillea younghusbandii phenylpropanoid glycoside compd A 200g, add starch dust 200g, Pulvis Talci 10g, magnesium stearate 5g, make granule, dry, incapsulates (1000).
Embodiment 3:
Get Incarvillea younghusbandii phenylpropanoid glycoside compd A 100g, microcrystalline Cellulose 250g, crospolyvinylpyrrolidone 70g, mixing, add ethanol in proper amount and granulate, dry, granulate, is adding carboxymethyl starch sodium 8g, magnesium stearate 4g, mixing, tabletting (1000).
Embodiment 4: antibacterial effect is tested
With escherichia coli, staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa for test organisms, adopt nephelometry, investigate the fungistatic effect of antibacterial.
The preparation of bacteria suspension: escherichia coli, staphylococcus aureus and Pseudomonas aeruginosa are aseptically seeded in 10ml nutrient broth medium respectively, 35 DEG C, cultivates 24h.Bacteria suspension physiological saline solution dilutes, and makes bacterial concentration reach 10 6cfu/ml.Candida albicans is aseptically seeded to 10ml and improves in Martin's fluid medium, 25 DEG C, cultivates 48h.Bacteria suspension physiological saline solution dilutes, and makes bacterial concentration reach 10 6cfu/ml.
The preparation of test liquid: take p-Hydroxybenzoate 0.2g respectively and p-Hydroxybenzoate 0.2g, phenethanol 5ml got in title (amount), be dissolved in 100ml nutrient broth medium, for escherichia coli, staphylococcus aureus and Pseudomonas aeruginosa test.Take p-Hydroxybenzoate 0.2g respectively and p-Hydroxybenzoate 0.2g, phenethanol 5ml got in title (amount), be dissolved in 100ml and improve in Martin's fluid medium, try out for Candida albicans.Get 10ml test liquid in test tube, autoclaving.Each test bacterium establishes 3 pipe test liquids (Incarvillea younghusbandii phenylpropanoid glycoside compd A low dose group, middle dosage group and high dose group), and establishes one group of control tube (blank medicine).Under aseptic condition, often prop up test tube and add bacteria suspension 0.2ml.Escherichia coli, staphylococcus aureus and Pseudomonas aeruginosa 35 DEG C, cultivate 24h, Candida albicans 25 DEG C, cultivates 48h.
According to " Chinese Pharmacopoeia 2010 version two " the antibacterial effect inspection technique guideline that annex specifies, inhibitory effect demonstration test is carried out to test liquid of the present invention.
Experimental result is as follows:
Incarvillea younghusbandii phenylpropanoid glycoside compd A low dose group 0.5mg/ml
Dosage group 2mg/ml in Incarvillea younghusbandii phenylpropanoid glycoside compd A
Incarvillea younghusbandii phenylpropanoid glycoside compd A high dose group 5mg/ml
Table 1 Incarvillea younghusbandii phenylpropanoid glycoside compd A low dose group inhibitory effect test organisms number decline lg value
Dosage group inhibitory effect test organisms number decline lg value in table 2 Incarvillea younghusbandii phenylpropanoid glycoside compd A
Table 3 Incarvillea younghusbandii phenylpropanoid glycoside compd A high dose group inhibitory effect test organisms number decline lg value
Table 4 blank group inhibitory effect test organisms number decline lg value
Table 1-4 data show, relative to blank group, Incarvillea younghusbandii phenylpropanoid glycoside compd A of the present invention basic, normal, high dosage group all has inhibitory action to each bacterioid.
Embodiment 5
The research of anti-mouse ear atopic dermatitis
1. reagent: DNF (DNFB), is dissolved in acetone-olive oil (3: 1, v/v) mixed solvent, is mixed with the solution of 0.15%w/v; Medicine of the present invention; Dexamethasone ointment (Shenzhen three nine-day periods after the winter solstice company).
2. the preparation of animal model: get male BALB/c mouse in 7 week age (body weight 18 ~ 22g), be divided into sensitization group and group of solvents at random, sensitization group 30, group of solvents 8.Allergen is not coated with 0.15%DNFB25ul and brings out dermatitis in mouse right ear both sides, acetone-olive oil (3: 1, the v/v) mixed solvent that group of solvents smears same volume (does not cause inflammation) in contrast.Observe Mus ear after one week and whether obvious tumefaction occurs, as the mark whether model is successfully prepared.
3. experiment grouping and administration: the mice of successful sensitization is divided into 3 groups at random, often organizes 8.Attack first 8 hours the last time, often organize and give Incarvillea younghusbandii phenylpropanoid glycoside compd A, the commercially available ointment of dexamethasone and adjuvant matched group (not containing active medicine) respectively, be 2mg/kg in reactive compound dosage, adjuvant matched group dosage is 2mg/kg.
4. the mensuration of observation index Mus ear thickness: test each group after last attack 6h digital display micrometer caliper (Kenta company, Singapore) measure mouse right ear thickness and with attack before Mus ear Thickness Ratio comparatively.
5. experimental result is shown in table 5.
The result of table 5. anti-mouse ear atopic dermatitis
Sample Mus ear thickens (micron)
Group of solvents 0.5
Adjuvant matched group 95.8
Incarvillea younghusbandii phenylpropanoid glycoside compd A group 44.3
The commercially available ointment of dexamethasone 56.9
From table 5 data, Incarvillea younghusbandii phenylpropanoid glycoside compd A of the present invention has the significant effect suppressing mouse ear dermatitis.

Claims (10)

1. a medicine, comprising Incarvillea younghusbandii phenylpropanoid glycoside compd A.
2. medicine as claimed in claim 1, wherein pharmaceutical dosage forms is tablet, capsule, drop pill, injection, freeze-dried powder, decoction, slow releasing preparation, powder, granule, suppository or aerosol.
3. medicine as claimed in claim 1 or 2, wherein also comprises excipient substance.
4. medicine as claimed in claim 3, wherein excipient substance comprises binding agent, filler, lubricant, diluent, solvent, slow-release material.
5. medicine as claimed in claim 4, wherein excipient substance comprises starch, dextrin, lactose, mannitol, microcrystalline Cellulose, hypromellose, polyvidone, cross-linking sodium carboxymethyl cellulose, Pulvis Talci, stearic acid, poloxamer, ethyl cellulose, acrylic resin.
6. the purposes of Incarvillea younghusbandii phenylpropanoid glycoside compd A in the medicine of preparation treatment bacteriological infection.
7. purposes as claimed in claim 6, wherein said antibacterial comprises escherichia coli, staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa.
8. the purposes of Incarvillea younghusbandii phenylpropanoid glycoside compd A in the medicine of preparation treatment dermatitis.
9. the purposes as described in any one of claim 6-8, meets subject patient and comprises mammal and birds.
10. purposes as claimed in claim 9, wherein meeting subject patient is people.
CN201610002241.9A 2016-01-05 2016-01-05 Novel drug for treating bacterial infection Pending CN105560257A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101152261A (en) * 2007-09-04 2008-04-02 北京理工大学 Application of phenyl ethyl alcohol glycosides and xylogen glycosides component in forsythia (fruit or leaf)
CN101264094A (en) * 2008-04-16 2008-09-17 西藏自治区高原生物研究所 Incarvillea younghusbandii phenylpropanoid glycoside composition and preparation and use thereof
CN101654692A (en) * 2009-08-04 2010-02-24 中山大学 Method for producing mullein glucoside monomeric compound
CN102304156A (en) * 2011-06-24 2012-01-04 浙江大东吴药业有限公司 Phenylethanoid glycoside components, and preparation method and application thereof
CN102920718A (en) * 2012-11-30 2013-02-13 苏州大学 Application of phenylethanoid glycoside monomeric compound
CN103816296A (en) * 2012-11-19 2014-05-28 苏州润新生物科技有限公司 Callicarpa bodinieri total glycosides extract as well as preparation method and application thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101152261A (en) * 2007-09-04 2008-04-02 北京理工大学 Application of phenyl ethyl alcohol glycosides and xylogen glycosides component in forsythia (fruit or leaf)
CN101264094A (en) * 2008-04-16 2008-09-17 西藏自治区高原生物研究所 Incarvillea younghusbandii phenylpropanoid glycoside composition and preparation and use thereof
CN101654692A (en) * 2009-08-04 2010-02-24 中山大学 Method for producing mullein glucoside monomeric compound
CN102304156A (en) * 2011-06-24 2012-01-04 浙江大东吴药业有限公司 Phenylethanoid glycoside components, and preparation method and application thereof
CN103816296A (en) * 2012-11-19 2014-05-28 苏州润新生物科技有限公司 Callicarpa bodinieri total glycosides extract as well as preparation method and application thereof
CN102920718A (en) * 2012-11-30 2013-02-13 苏州大学 Application of phenylethanoid glycoside monomeric compound

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
KAREL SMEJKAL ET AL: "Antiradical Activity of Paulownia tomentosa (Scrophulariaceae) Extracts", 《MOLECULES》 *
吴娟: "藏角蒿花的化学成分研究", 《中国优秀硕士论文全文数据库医药卫生科技辑》 *
宋景春 等: "《弥散性血管内凝血中西医结合治疗学》", 31 December 2014, 军事医学科学出版社 *
邹国栋等: "HP L C法测定紫珠叶中毛蕊花糖苷的含量", 《药物分析杂志》 *

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Application publication date: 20160511