CN104016923B - Phenytoin derivant and its production and use - Google Patents
Phenytoin derivant and its production and use Download PDFInfo
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- CN104016923B CN104016923B CN201410009188.6A CN201410009188A CN104016923B CN 104016923 B CN104016923 B CN 104016923B CN 201410009188 A CN201410009188 A CN 201410009188A CN 104016923 B CN104016923 B CN 104016923B
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- phenytoin
- silver
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- derivant
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- 0 *C(NC1(c2ccccc2)c2ccccc2)=NC1=O Chemical compound *C(NC1(c2ccccc2)c2ccccc2)=NC1=O 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/74—Two oxygen atoms, e.g. hydantoin with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to other ring members
-
- Y—GENERAL 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides one and there is the phenytoin derivant of structure (I).Present invention also offers the preparation method of the phenytoin derivant shown in structure (I) and the purposes in terms of preparation promotes the external used medicine of wound surface healing and suppression bacterial wound infection thereof.Present invention also offers a kind of external used medicine promoting wound surface healing and suppression wound infection.
Description
Technical field
The invention belongs to medicinal chemistry art, in particular to phenytoin derivant and preparation method thereof and
Purposes.
Background technology
Skin is the organ that human body is maximum, it make internal various tissue and organ from physical property, mechanicalness,
Chemical and the invasion and attack of pathogenic microorganism.When skin sustains damage, and wound is bigger, it is difficult to quickly heal
Virus and the harmful substance that can cause the external world intrude into inside of human body, cause the disease such as infection suppurates of wound
Shape.The factors such as skin is infected all can cicatrize a wound difficulty.Wound infection simultaneously, in will causing human body
Defense mechanism produce response, cause the reaction such as a series of inflammation.
Traditional Wound healing and bone regeneration medicine being applied to clinic, is used to suppress wound infection, for promoting mostly
The effect of wound healing is the most inconspicuous.Especially for big wound, wound healing time is long, easily infects,
Have a strong impact on work and the life of patient.
Accordingly, it would be desirable to one can infection, the medicine of wound healing, this medicine can be promoted again rapidly
Will well benefit patient, have good market prospect simultaneously.
Summary of the invention
In order to obtain a kind of external used medicine promoting wound healing and suppression bacterial wound infection, the present invention is led to
Crossing chemical reaction and prepared a kind of phenytoin derivant, this compound has a structure that
According to systematic nomenclature, this compound is 5,5-diphenyl-2,4-imidazolidimedione silver salt, and inventor will
This Compound nomenclature is phenytoin silver.
Present invention also offers the preparation method of phenytoin silver, including: a) utilize phenytoin Sodium at acid bar
Phenytoin is prepared under part；B) preparation silver ammino solution；C) it is made into benzene with the weak ammonia dissolving phenytoin of 2% appropriate
English solution, dropwise instills silver ammino solution in phenytoin solution, generates the phenytoin silver of precipitated form.At this
In preparation method, wherein, pH value is adjusted to realize acid condition to 6 with the hydrochloric acid of 10%.
Present invention also offers phenytoin silver outside preparation promotes wound surface healing and suppression wound infection
By the purposes in terms of medicine.Wherein promote that wound surface healing is included in skin damage and occurs promoting wound during wound
The healing incrustation in face.Suppression wound infection include suppress because of bacterial wound infection cause wound inflammation, suppuration.
Antibacterial is in escherichia coli, Gram-positive, negative bacterium, drug-resistant staphylococcus aureus, bacillus pyocyaneus or mycete
Plant or multiple.
Present invention also offers a kind of external used medicine promoting wound surface healing and suppression wound infection, this medicine
Thing comprises the phenytoin silver as active component or its pharmaceutically acceptable acid, alkali, salt or ester, and medicine
Use adjuvant.The dosage form of this external used medicine selected from powder, suspensoid, gel, opacifiers, colloid solution agent,
One in mucilage, ointment, plaster or patch.
By the phenytoin silver of the present invention being carried out bacteriostatic experiment and the wound healing carried out with mice
It is experimentally confirmed that the phenytoin silver prepared by the present invention has the most antibacterial and bactericidal action, and to wound
Healing play extraordinary effect, also play during wound healing simultaneously and well suppress wound
The effect infected.
Accompanying drawing explanation
Fig. 1 shows the synthetic route chart of phenytoin silver.
Fig. 2 shows the result that phenytoin silver infrared absorption spectroscopy is tested.
Fig. 3 shows Bactericidal test result figure.
Fig. 4 shows mice Wound Healing Experiments result figure.
Detailed description of the invention
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clearly
Chu, it is fully described by.The following stated is only the preferred embodiments of the present invention, is not limited to this
Bright, for a person skilled in the art, the present invention can have various modifications and variations.All in the present invention
Spirit and principle within, any modification, equivalent substitution and improvement etc. made, should be included in the present invention
Protection domain within.
The present invention has been prepared as compound phenytoin silver by chemical reaction, by infrared absorption spectroscopy and atom
The phenytoin silver of preparation is identified by absorption spectrum.By pressing down of a series of experiment detection phenytoin silver
Bacterium activity and the activity of promotion wound healing.Detailed description of the invention is as follows:
In the following example, test material used and source thereof include:
Phenytoin Sodium and silver nitrate are purchased from sky, the north, Tianjin medical chemistry purchased from Shanghai Sheng Gong biotech firm, ammonia
Chemical reagent work, escherichia coli are from medicine joint study high-flux medicaments sifting center, the world, Tianjin.LB cultivates
Carnis Bovis seu Bubali cream and peptone in base are all purchased from OXOID company.Experiment is used C57/BL mice be purchased from
Military Medical Science Institute's Experimental Animal Center.
Embodiment 1: the synthesis of phenytoin silver and qualification
The synthesis (seeing Fig. 1) of 1.1 phenytoin silver
The preparation of phenytoin: 10g phenytoin Sodium is dissolved in water, the hydrochloric acid with 10% is adjusted pH value to 6, is analysed
Go out white precipitate, sucking filtration, crystallization a small amount of washing, vacuum drying, prepare the phenytoin being dried.
The configuration of silver ammino solution: weigh 1.68g AgNO3In dropwise instill the weak ammonia of 2% and constantly vibrate,
Till the precipitation initially produced is dissolved just.
The synthesis of phenytoin silver: weigh the weak ammonia that dry phenytoin 2.75g is dissolved into the 2% of 50mL
In, make phenytoin solution.Under ultrasound condition, dropwise instill in the ammonia spirit of the 2% of phenytoin
State the silver ammino solution of preparation, have white precipitate to generate.Gained precipitation is phenytoin silver.Sucking filtration will be precipitated,
Washing twice with the weak ammonia of 2%, distillation washing once, is then washed once with dehydrated alcohol, is dried, weighs.
Taking the content of a part of product atomic absorption spectrum detection silver, separately taking a part carries out infrared spectrum inspection simultaneously
Survey.
Weigh 1g phenytoin silver, resuspended with the gelatin solution of 10mL1%, it is prepared as concentration and is about 0.1g/mL
The gelatin solution of phenytoin silver, for carrying out the wound healing assay of bacteriostatic activity test and mice.
The qualification of 1.2 phenytoin silver
Atomic absorption spectrum testing result (is provided by biotechnology (Tianjin) company limited of vast alliance): atom
Absorption spectrum testing result shows, in obtained phenytoin silver, the content of silver is 31.2%, with phenytoin
In silver, the theoretical content of silver is basically identical, illustrates that the preparation of phenytoin silver is successful.
Infrared spectrum testing result (is provided by Nankai University's macromolecule institute's infrared test center): appropriate by benzene
English and the contrast of infrared spectrum testing result (see accompanying drawing 2) of phenytoin silver, we it appeared that: with benzene
The infrared spectrum of appropriate English is compared, 3273cm in phenytoin pale rose colour external spectrum-1The characteristic absorption peak of the N-H at place
Disappear, and at 1640cm-1Place adds the characteristic absorption peak of C=N.Above testing result explanation phenytoin
There occurs reaction with silver ammino solution, generate phenytoin silver, the preparation of phenytoin silver is successful.
Embodiment 2 phenytoin silver bacteriostatic activity is tested
2.1 experimental techniques:
1) take the escherichia coli glycerol stock of 5 μ L, be inoculated in the LB liquid medium of 5mL, be placed in
In 37 DEG C of shaking tables, 220rpm/min, incubated overnight；
2) take the escherichia coli 200 μ L of overnight incubation, after diluting 10 times, take 200 μ L, coat nothing
On anti-solid LB media；
3) filter paper is cut into the disk of a diameter of 1cm, is dipped in distilled water mesohigh sterilizing；
4) will cover with colibacillary culture medium and be divided into four parts, two parts are experimental group, and two parts are right
According to group.Experimental group patch on thalline is moistened with the filter paper of phenytoin silver suspension, and matched group patch is moistened with aseptic steaming
The filter paper of distilled water.Formed with or without inhibition zone around the filter paper of observation experiment group and matched group after 24h and formed
The size of inhibition zone.
2.2 bacteriostatic activity test results:
Result is as it is shown on figure 3, have obvious inhibition zone to occur around phenytoin silver group filter paper, and display benzene is appropriate
The good fungistatic effect of Ying Yinyou.
Embodiment 3 phenytoin silver promotes Wound healing activity test
3.1 experimental technique
1) taking three healthy SD rats, the left and right sides shears at every rat back cuts one respectively
The circular wound of a diameter of 1cm, the degree of depth of wound is roughly the same；
2) on back, the side circular wound of every mouse, smear the phenytoin Gelatin suspension conduct produced
Experimental group, opposite side smears the gelatin solution without phenytoin silver of equivalent as comparison；
3) observe the healing rate of rat wound, healing, wound swelling, inflammation every day, ooze out
Number, the incrustation degree of wound surface and the healing time of thing.
3.2 Wound healing activity test results (seeing Fig. 4):
After being administered three days, the wound healing of the mouse smearing phenytoin silver group substantially and is formed a scab, and does not infect
Sign.The wound of matched group mouse is almost without healing, and wound is red and swollen, has infection sign.It is therefore seen that benzene
Appropriate English silver has the effect well promoting wound healing.
Although an embodiment of the present invention has been shown and described, for those of ordinary skill in the art
For, it is possible to understand that without departing from the principles and spirit of the present invention can be to these embodiments
Carry out multiple change, revise, replace and modification, the scope of the present invention by claims and etc.
Jljl limits.
Claims (1)
1. a preparation method for phenytoin derivant, including:
A) 10g phenytoin Sodium being dissolved in water, the hydrochloric acid with 10% adjusts pH value to 6, separates out white precipitate, sucking filtration, crystallization a small amount of washing, vacuum drying, prepares the phenytoin being dried；
B) preparation silver ammino solution: weigh 1.68g AgNO3In dropwise instill the weak ammonia of 2% and constantly vibrate, till the precipitation initially produced is dissolved just；
C) weigh described dry phenytoin 2.75g to be dissolved in the weak ammonia of 2% of 50mL, make phenytoin solution, under ultrasound condition, in the ammonia spirit of the 2% of phenytoin, dropwise instill the described silver ammino solution of preparation, white precipitate is had to generate, gained precipitation is phenytoin silver, by described precipitation sucking filtration, washes twice with the weak ammonia of 2%, distillation washing is once, then wash once with dehydrated alcohol, be dried, weigh；
Wherein, described phenytoin derivant, there is following structural formula:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410009188.6A CN104016923B (en) | 2014-01-08 | 2014-01-08 | Phenytoin derivant and its production and use |
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| CN201410009188.6A CN104016923B (en) | 2014-01-08 | 2014-01-08 | Phenytoin derivant and its production and use |
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| CN104016923A CN104016923A (en) | 2014-09-03 |
| CN104016923B true CN104016923B (en) | 2016-08-31 |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106075556A (en) * | 2016-06-02 | 2016-11-09 | 四川奎星医用高分子制品有限责任公司 | Containing the medical recombination chitosan gel promoting wound healing medicine |
| CN105999362A (en) * | 2016-06-02 | 2016-10-12 | 四川奎星医用高分子制品有限责任公司 | Medical composite alginate dressing containing antibacterial drug and preparation method thereof |
| CN105854069A (en) * | 2016-06-02 | 2016-08-17 | 四川奎星医用高分子制品有限责任公司 | Alginate dressing containing wound-healing promoting medicine and preparing method thereof |
| CN106880765B (en) * | 2017-03-13 | 2020-05-12 | 牡丹江医学院 | Powder for promoting wound healing |
| CN107998071B (en) * | 2017-12-02 | 2020-06-19 | 南开大学 | Method for improving stability of phenytoin silver and phenytoin silver external preparation |
| CN110174363A (en) * | 2019-01-09 | 2019-08-27 | 北京九强生物技术股份有限公司 | Glucose-6-phosphate dehydrogenase mutant and its purposes in preparation detection reagent |
| CN111068103B (en) * | 2020-02-06 | 2020-12-18 | 牡丹江医学院 | Long-acting antibacterial gel dressing for operation wound and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0151942A1 (en) * | 1984-01-16 | 1985-08-21 | Sigmund E. Lasker | Diphenyl hydrantoin silver complex and uses thereof |
| WO1992018098A1 (en) * | 1991-04-10 | 1992-10-29 | Capelli Christopher C | Antimicrobial compositions useful for medical applications |
| EP0593042A1 (en) * | 1992-10-14 | 1994-04-20 | Matsushita Electric Industrial Co., Ltd. | Antiviral composition |
| CN1466419A (en) * | 2000-09-29 | 2004-01-07 | ���Ͽع�����˾ | Stabilized compositions having antibacterial activity |
-
2014
- 2014-01-08 CN CN201410009188.6A patent/CN104016923B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0151942A1 (en) * | 1984-01-16 | 1985-08-21 | Sigmund E. Lasker | Diphenyl hydrantoin silver complex and uses thereof |
| WO1992018098A1 (en) * | 1991-04-10 | 1992-10-29 | Capelli Christopher C | Antimicrobial compositions useful for medical applications |
| EP0593042A1 (en) * | 1992-10-14 | 1994-04-20 | Matsushita Electric Industrial Co., Ltd. | Antiviral composition |
| CN1466419A (en) * | 2000-09-29 | 2004-01-07 | ���Ͽع�����˾ | Stabilized compositions having antibacterial activity |
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| CN104016923A (en) | 2014-09-03 |
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