CN1433756A - Use of potassium dehydroandrographolide succinate in preparing external used medicine for treating dermatosis - Google Patents
Use of potassium dehydroandrographolide succinate in preparing external used medicine for treating dermatosis Download PDFInfo
- Publication number
- CN1433756A CN1433756A CN 03117332 CN03117332A CN1433756A CN 1433756 A CN1433756 A CN 1433756A CN 03117332 CN03117332 CN 03117332 CN 03117332 A CN03117332 A CN 03117332A CN 1433756 A CN1433756 A CN 1433756A
- Authority
- CN
- China
- Prior art keywords
- andrographolide
- hsv
- pharmaceutical composition
- herpes
- acv
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to an application of chuanhuang (potassium dehydroandrographolid succinate) in preparation of medicine for external application of curing dermatosis. The described dermatosis includes herpes zoster and herpes genitalis, etc. It can obtain good therapeutic effect.
Description
Technical field
The present invention relates to a kind of purposes of Andrographolide, the particularly Andrographolide purposes in the dermopathic medicine for external use of preparation treatment.
Background technology
At present, Andrographolide generally is injectable powder or injection, is used for the disease that virus such as upper respiratory tract infection causes, but to the dermatosis that some virus causes, convenient inadequately and safety when adopting the mode of injection to use.Therefore, it is necessary seeking a kind of safer, convenient, effective application method, has not yet to see the report about the external purposes research of Andrographolide.
Summary of the invention
The new purposes that the purpose of this invention is to provide Andrographolide, i.e. new application in pharmacy.More specifically, provide a kind of Chuanhuning preparation of external, than injection, more convenient patient uses, and can directly act on the affected part.
The object of the present invention is achieved like this:
The purposes of Andrographolide in the dermopathic medicine for external use of preparation treatment is provided.
The herpes that described dermatosis causes for virus, described dermatosis is herpes zoster, genital herpes.
Also provide the treatment that contains Andrographolide dermopathic pharmaceutical composition, contain Andrographolide 0.001%～75.60% at least, by weight percentage (following composition is calculated all by weight percentage).
Further, contain Andrographolide 0.001-27.55%.
Further, contain Andrographolide 0.5-16.5%.
Above-mentioned pharmaceutical composition is prepared to external preparation, and described preparation is a unguentum, and specifically, described preparation is a gel.
The dermopathic pharmaceutical composition of treatment of the present invention, can also form by following composition: with percentage by weight, Andrographolide 0.001-75.60%, substrate 0.001-30.075%, wetting agent 2.0-84.0%, metal chelating agent 0.01-24.9
, antioxidant 0.01-39
, antiseptic 0.01-299
Further, the composition of described pharmaceutical composition is: Andrographolide 0.001-27.55%, substrate 0.001-25.46%, wetting agent 9.9-75.9%, metal chelating agent 0.1-17.8
Antioxidant 1.0-18.7
, antiseptic 5-164
Further, the composition of described pharmaceutical composition is: Andrographolide 0.5-16.5%, substrate 0.5-15.0%, wetting agent 11.5-65.5%, metal chelating agent 0.5-10.9
Antioxidant 5.00-14.50
, antiseptic 17-95
The invention has the beneficial effects as follows that herpes especially herpes zoster, genital herpes are had excellent curative, and easy to use, can directly act on the affected part.
The specific embodiment
Preparation technology: 1) by above-mentioned weight ratio scope get principal agent, pharmaceutically commonly used medicine for external use substrate adds an amount of distilled water to stir evenly into pasty state standby.2) get an amount of distilled water, after the dissolving of adding metal chelating agent agitating heating, add cosolvent, PH regulator, antioxidant, add 1 then) middle heating and stirring.3) add 2 after getting stabilizing agent, wetting agent, antibacterial mixing) in stir.4) in 3) in adding distil water an amount of, stirring and dissolving is filtered to clarification, check, fill gets finished product.Prepare the Andrographolide gel by above method, also can be prepared into other unguentum, the pharmacological testing of the line correlation of going forward side by side.Pharmacological testing:
Experiment 1: the external anti-herpes simplex virus test of Andrographolide test material one, medicine
Andrographolide succinic acid half fat monopotassium salt, white powder, lot number: 990701, Yibin pharmaceutical factory of Wuliangye group provides by Yibin, Sichuan Province.With injection [authentication code: the accurate word (1985) of medicine is defended No. 003181 in the river, lot number: 0007011,200mg/10ml/ props up] as using liquid.
Acyclovir (ACV) injection, the 250mg/ bottle, lot number 970105 is produced by benefit pharmaceutical factory of Hubei Province's institute of Pharmaceutical Industry section, is that 1mg/ml is as using liquid with 5% sodium lactonic solution dilution.
Acyclovir ointment: 10 grams: 0.3 gram, every 10 gram dress.The accurate word XF19990947 of traditional Chinese medicines, Chengdu, Hubei pharmaceutical Co. Ltd, lot number 000701.Two, virus
Herpes simplex virus I-type (HSV-I) Sm44 strain is available from Ministry of Public Health medicine biology
Goods calibrating institute.HSV-I9608 is a clinical separation strain.Three, cell
The Vero cell is available from Ministry of Public Health pharmaceutical biological product calibrating institute.Four, reagent and instrument
RPMI-1640 U.S. Gibco company
Hyclone Britain import packing company
Tissue Culture Plate U.S. Corning company
CO2 incubator U.S. Shel-Lab test method one. at first measure Andrographolide and ACV maximal non-toxic concentration (TD0) to the Vero cell; Adopt pathogenic histiocyte observational method (CPE) to measure the virulence of HSV-I then.Last reuse Andrographolide and ACV act on and have infected viral cell monolayer, according to the mensuration of the maximal non-toxic concentration (TD0) of medicine pair cell.
With RPMI-1640 liquid Andrographolide (0.4mg/ml) is diluted in proportion in the cell monolayer of Vero of 96 well culture plates, adds variable concentrations Andrographolide and ACV medicinal liquid respectively, put 37 ℃, 5%CO
296h in the incubator, the observation of cell pathological changes is measured its maximal non-toxic concentration to the Vero cell.Two, Bing Du toxicity test
Adopt 96 porocytes to cultivate the Vero cell monolayer, inoculate different dilution HSV-I virus liquid (10
-1～10
-8), each dilution factor is inoculated 4 holes, puts 37 ℃ and cultivates 96h, and the observation of cell pathological changes is decided to be this virus half cell infection concentration (1 TCID with the high dilution that 2 porocyte pathological changes occur
50).Three, Andrographolide extracorporeal antivirus effect experiment
Cytopathy (CPE) inhibition method adds different dilution Andrographolides or ACV liquid earlier in the Vero cell monolayer of 96 porocyte culture plates, medicinal liquid is removed in the 2h hypsokinesis, adds 100TCID in every hole again
50HSV-I, 37 ℃, 5%CO
2In the incubator, observation of cell pathological changes behind the 96h.Set up the blank cell hole of virus control in the experiment.Calculate half cytopathy inhibition degree drug level (IC with the Reed-Muench method
50).Result of the test one, Andrographolide, ACV the results are shown in Table 1 to the maximal non-toxic concentration (TD0) of Vero cell, and Andrographolide is 1mg/ml to the maximal non-toxic concentration of Vero cell, and ACV is 0.02mg/ml to Vero cell Cmax.
Table 1 Andrographolide, AVC are to the maximal non-toxic concentration (TD of Vero cell
0)
Concentration (mg/ml) medicine hole number
21 0.5 0.25 0.125 0.062 0.031 0.015 cells contrast Andrographolide 1 ++-------
2??????++???-????-?????-??????-???????-???????-????????????????-
3??????++???-????-?????-??????-???????-???????-????????????????-
4??????++???++???-?????-??????-???????-???????-????????????????-ACV???????1??????+????-????-?????-??????-???????-???????++???????????????-
2??????++???-????-?????-??????-???????-???????++
3??????++???-????-?????-??????-???????-???????+????????????????-
4 ++-----++-annotate: "-" acellular pathological changes, "+" 25% cytopathy, " ++ " 50% cytopathy.Two, virus virulence measurement result cytopathy (CPE) inhibition method is measured HSV-1 Sm44 strain, and the virulence of HSV-I9608 strain the results are shown in Table 2.
Table 2 HSV virus virulence measurement result virus CPE method (TCID
500.1ml) HSV-I Sm44 10
-7HSV-I 9,608 10
-5Three, Andrographolide, the external anti-HSV result of the test of ACV
Use the CPE method, detected Andrographolide, ACV vitro inhibition activity respectively, the results are shown in Table 3 the HSV-1 of different virulence.1, HSV-I suppresses active
Test by two batches shows: the half cytopathy inhibition concentration (IC of CPE method Andrographolide
50) be 0.71 ± 0.08mg/ml, ACV is 0.09 ± 0.03mg/ml, shows the poor activity of Andrographolide than the external anti-HSV-I of ACV.
See Table 3.
Table 3 Andrographolide, the external anti-HSV-I activity of AVC (CPE method)
Andrographolide AVC virus batch dosage
(mg/ml) lesion degree (%) IC
50(mg/ml) lesion degree (%) IC
50(mg/ml)
1??????1??????????43.75??????????????????????????0
0.5????????56.25??????????????????????????0
0.25???????75??????????????0.71???????????0??????????????0.09
0.125??????81.25??????????????????????????18.75
0??????????93.75??????????????????????????100HSV-ISm44
2??????1??????????43.75??????????????????????????0
0.5????????56.25??????????????????????????0??????????????0.09
0.25???????75?????????????????????????????0.71???????????0
0.125??????81.25??????????????????????????12.50
0??????????81.25??????????????????????????100
Meansigma methods 0.71 ± 0.08 0.09 ± 0.03
1??????1??????????43.75??????????????????????????0
0.5????????50?????????????????????????????0
0.25???????81.25???????????0.88???????????0??????????????0.09
0.125??????93.75??????????????????????????25
0??????????93.75??????????????????????????93.75HSV-+19705
2??????1??????????43.75??????????????????????????0
0.5????????56.23??????????????????????????0??????????????0.09
0.25???????81.25???????????0.71???????????0
0.125??????93.75??????????????????????????25.00
0??????????93.75??????????????????????????100
Meansigma methods 0.8 ± 0.06 0.09 ± 0.01
Experiment 2: anti-herpes simplex virus experiment in the Andrographolide body
Andrographolide gel treatment guinea pig skin infects the experiment of HSV-I
Experiment material
1, medicine: 5% Andrographolide gel, 8% Andrographolide gel and blank gel are to be provided by Yibin pharmaceutical factory of Wuliangye group, lot number 001203, and 3%ACV ointment is by Hubei Province
2, virus: HSV-I Sm44 strain, available from the Ministry of Public Health biological products assay institute.
3, cell, reagent and instrument: with experiment 1.
4, animal: Cavia porcellus, body weight 250-300g/ only, available from Chengdu Biological Products Inst., Ministry of Public Health management of laboratory animal center, the animal quality certification number: (1995) doctor pipe can No. 24101106.
Test method
1, HSV-I Sm44 infects the virulence (ID of guinea pig skin
50) measure guinea pig back after the depilation of 8% sodium sulfide, stab epidermis with percussopunctator in four sub-districts, its back, use different dilution HSV-I Sm44 virus liquid 10 then
-4-10
-7TCID
50/ 0.1ml infects skin lesion, and 0.1ml/ only.From infecting HSV-I Sm44 second day, observe and write down skin day by day and be inflamed and the herpes lesion degree, observed altogether 7 days, score according to following standard: red: 1 minute; Go out phlycten 1-5: 3 minutes; Go out bleb＞10: 10 minutes.Accumulative total is divided high more, shows that the skin lesion degree is heavy more.The highest the adding up of every Cavia porcellus is divided into 10 fens, according to the skin lesion degree, calculates ID
50
2, the anti-HSV-ISm44 viral suspension of Andrographolide gel 0.1ml drops in guinea pig back depilation skin lesion place, begins in second day (24h) with 5% and 8% Andrographolide gel and blank gel each group test Cavia porcellus to be smeared, and smears once totally 3 days every day.
The experiment contrast group adopts 3%ACV ointment to smear, and method is the same.
Day by day observe and write down the sick damage degree of guinea pig skin, from smearing medicine-feeding, observed altogether 6 days, score is also calculated and is respectively organized the suppression ratio of medicine to skin lesion, carries out statistical procedures.
Suppression ratio=(virus control group-experimental group average)/virus control class mean * 100%
Experimental result: 1.HSV-I Sm44 infects the virulence (ID of Cavia porcellus
50) measurement result sees Table 4.10
-6TCID
50The viral liquid of/0.1ml is promptly represented 1 ID
50, then can make 50% Cavia porcellus pathological changes occur.Adopt 10 ID in this experiment
50Infect Cavia porcellus skin lesion place, then due viral liquid is 10
-5TCID
50/ 0.1ml.
Table 4 Cavia porcellus skin lesion place infects the ID of HSV-Ism44
50HSV-I titre Cavia porcellus quantity skin lesion accumulation accumulation accumulative perception
Pathological changes branch/total points (TCID
50/ 0.1ml) (only) mark/total points normally divides disease damage branch (%) 10-4 10 98/,100 8 496 496/504 98.410-5 10 70/,100 68 304 304/372 81.710-6 10 52/,100 164 164 164/328 50.010-7 10 30/,100 304 60 60/,364 19.72, the anti-guinea pig skin of potassium dehydroandrographolide succinate gel to infect 10ID50The evaluation of pesticide effectiveness of HSV-I Sm44
The results are shown in Table 5, each treatment group all can obviously alleviate the skin lesion degree that guinea pig skin infects, 8% Andrographolide gel better efficacy wherein, and the skin lesion suppression ratio reaches 80.7%, curative effect and 3%ACV (the skin lesion suppression ratio is 82.5%) similar (P＞0.05).The skin lesion suppression ratio of 5% Andrographolide gel is 73.6%, and curative effect is poorer than 3%ACV.
Table 5 Andrographolide gel treatment guinea pig skin infects 10ID
50HSV-ISm44 result
Cavia porcellus average suppression ratio P value
Guinea pig skin disease damage degree every day (X) group (only) 123456 (%) 5% potassium dehydroandrographolide succinate 10 1 2.4 4.5 2.2 0.9 0.4 1.85 73.6＜0.058% potassium dehydroandrographolide succinate 10 12 2.4 1.8 0.6 0.3 1.35 80.7＜0.053%AVC 10 1 1.8 2.6 1.3 0.5 0.2 1.23 82.5 virus control groups 10 1 5.1 6.8 9.2 10 10 7.01-blank 10 1 4.8 5.7 7.9 9.2 9.6 6.36 0.09
Annotate: the P value is that 5% or 8% Andrographolide gel and 3%ACV ointment compare
Experiment conclusion
1, the external anti-HSV-I's of Andrographolide is active relatively poor, with the Andrographolide IC of CPE method mensuration
50Value is 0.71 ± 0.08mg/ml, differs big (P＜0.05) with the ACV activity.
2,8% Andrographolide gel can effectively be treated HSV-I Sm44 and infected damage due to the guinea pig skin, and its pathological changes suppression ratio is 80.7%, with 3%ACV ointment (82.5%) therapeutic equivalence (P＞0.05).
Above-mentioned pharmacological testing shows when Andrographolide is smeared administration in external, herpes is had the good curing effect, for the treatment of herpes especially herpes zoster, genital herpes provides a kind of new convenient and safe route of administration.
Embodiment is as follows more specifically:
Antioxidant (B):
| Principal agent (g) | Substrate (g) | Wetting agent (ml) | Metal chelating agent (g) | Antioxidant (g) | Antiseptic | ||||||
| Embodiment 1 | ??50 | ??H3 | ?40 | ?G2 | ?300 | ??C2 | ????0.5 | ??B1 | ????1.0 | ??F1 | ??0.1％ |
| Embodiment 2 | ??110 | ??H2 | ?70 | ?G4 | ?800 | ??C2 | ????2.0 | ??B4 | ????2.0 | ??F2 | ??65ml |
| Embodiment 3 | ??185 | ??H1 | ?200 | ?G3 | ?1500 | ??C1 | ????4.5 | ??B6 | ????8.5 | ??F5 | ??40ml |
| Embodiment 4 | ??250 | ??H4+H3 | ?160 | ?G1 | ?1600 | ??C3 | ????10 | ??B5 | ????5.5 | ??F4 | ??80ml |
| Embodiment 5 | ??500 | ??H7 | ?210 | ?G2 | ?2260 | ??C3 | ????10 | ??B2 | ????15 | ??F7 | ??105ml |
| Embodiment 6 | ??850 | ??H5 | ?300 | ?G1 | ?3500 | ??C2 | ????18 | ??B3 | ????10 | ??F6 | ??125ml |
| Embodiment 7 | ??1500 | ??H6 | ?800 | ?G4 | ?4000 | ??C1 | ????25 | ??B5 | ????20 | ??F3 | ??200ml |
B1: ascorbic acid B2: glutathion B3:L-cysteine hydrochloride
B4:L-cysteine B5: thiourea B6: sodium thiosulfate metal chelating agent (C):
C1: ethylenediaminetetraacetic acid C2: disodium EDTA
C3: calcium disodium edathamil salt wetting agent (G):
G1: Macrogol 4000 G2: propylene glycol G3: glycerol
G4: propylene glycol diacetate substrate (H):
H1: Acritamer 940 H2:CMC-Na H3: vaseline
H4: anhydrous lanolin H5: glycerin gelatine H6: Ka Bopuer
H7: PEG400
Claims (9)
1, the purposes of Andrographolide in the dermopathic medicine for external use of preparation treatment.
2, Andrographolide purposes as claimed in claim 1, the herpes that described dermatosis causes for virus.
3, Andrographolide purposes as claimed in claim 1, described dermatosis is herpes zoster, genital herpes.
4, contain the dermopathic pharmaceutical composition of treatment of Andrographolide, contain Andrographolide 0.001-75.60% at least, by weight percentage.
5, pharmaceutical composition as claimed in claim 4 is characterized in that, contains Andrographolide 0.001-27.55%, by weight percentage.
6, pharmaceutical composition as claimed in claim 4 is characterized in that, contains Andrographolide 0.5-16.5%, by weight percentage.
7, as claim 4,5,6 described pharmaceutical compositions, it is characterized in that described pharmaceutical composition is prepared to external preparation.
8, pharmaceutical composition as claimed in claim 7 is characterized in that, described preparation is a unguentum.
9, pharmaceutical composition as claimed in claim 8 is characterized in that, described preparation is a gel.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03117332 CN1433756A (en) | 2003-02-21 | 2003-02-21 | Use of potassium dehydroandrographolide succinate in preparing external used medicine for treating dermatosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03117332 CN1433756A (en) | 2003-02-21 | 2003-02-21 | Use of potassium dehydroandrographolide succinate in preparing external used medicine for treating dermatosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1433756A true CN1433756A (en) | 2003-08-06 |
Family
ID=27634338
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03117332 Pending CN1433756A (en) | 2003-02-21 | 2003-02-21 | Use of potassium dehydroandrographolide succinate in preparing external used medicine for treating dermatosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1433756A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008519066A (en) * | 2004-11-08 | 2008-06-05 | コーネル リサーチ ファンデーション インコーポレーティッド | Andrographolide derivatives for the treatment of viral infections |
| CN101926755B (en) * | 2009-09-25 | 2012-08-22 | 中国中医科学院中药研究所 | In-situ gel preparation of potassium dehydroandrographolide succinate and preparation method thereof |
-
2003
- 2003-02-21 CN CN 03117332 patent/CN1433756A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008519066A (en) * | 2004-11-08 | 2008-06-05 | コーネル リサーチ ファンデーション インコーポレーティッド | Andrographolide derivatives for the treatment of viral infections |
| US8445533B2 (en) * | 2004-11-08 | 2013-05-21 | Cornell Research Foundation, Inc. | Andrographolide derivatives to treat viral infections |
| CN101926755B (en) * | 2009-09-25 | 2012-08-22 | 中国中医科学院中药研究所 | In-situ gel preparation of potassium dehydroandrographolide succinate and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101062343A (en) | External application Chinese traditional medicine for treating dermatoma, tinea, wart and herpes | |
| CN101953841A (en) | Swine eperythrozoonosis-resisting compound long-acting oxytetracycline injection and preparation method thereof | |
| CN1230117A (en) | Pharmaceutical compsns. with antimicrobial activity | |
| CN1907264A (en) | Compound sulfonamide suspensoid and its preparing process | |
| CN101036695A (en) | Oil-in-water type nanometer emulsion elecampane oil and litsea citrata oil and the method for preparing the same | |
| CN105753719B (en) | A kind of Syprine Hydrochloride compound | |
| CN1433756A (en) | Use of potassium dehydroandrographolide succinate in preparing external used medicine for treating dermatosis | |
| CN1101214C (en) | External use disinfectant anagesic and production thereof | |
| CN102283804A (en) | Meglumine adenosine cyclophosphate injection and preparation method thereof | |
| CN1771937A (en) | Externally applied podophyllotoxin ointment and its prepn | |
| CN1748758A (en) | Dragon's blood gel preparation and its preparing method | |
| CN1555702A (en) | Excellent primary herbicide for wheat field | |
| CN1887271A (en) | Azithromycin liposome composition medicine and its prepn process | |
| CN103142461A (en) | Gel for vaginas and preparation method thereof | |
| CN1433758A (en) | Use of potassium dehydroandrographolide succinate in preparing external used medicine | |
| CN1107501C (en) | Albendazole emulsion | |
| CN1742723A (en) | Medicine composition containing temozolomide-8-carboxylic ether and use of such compound for preparing anti-tumor medicine | |
| CN1762386A (en) | Bone density-increasing and senility-postponing capsule formulation | |
| CN104086548B (en) | A kind of matrine derivative and application thereof | |
| CN1718183A (en) | Neo-garcinolic acid prepn. for injection use, prepn. method and use thereof | |
| CN1249224C (en) | Superoxide dismutase composition and preparation method thereof | |
| CN1868483A (en) | Injection for treating eperythrozoonosis of domestic animal and its prepn. method | |
| CN1544475A (en) | Sulfated Polyguluronic Acid Ester and its preparation method and uses | |
| CN1255102C (en) | Dripping pills of compound allantoin | |
| CN1269479C (en) | Externally used liquid preparation containing fibrauretine and its application on genital tract, oral cavity and upper respiratory tract |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |