CN103989626A - Aciclovir gel composition with improved performance - Google Patents
Aciclovir gel composition with improved performance Download PDFInfo
- Publication number
- CN103989626A CN103989626A CN201410184833.8A CN201410184833A CN103989626A CN 103989626 A CN103989626 A CN 103989626A CN 201410184833 A CN201410184833 A CN 201410184833A CN 103989626 A CN103989626 A CN 103989626A
- Authority
- CN
- China
- Prior art keywords
- weight
- compositions
- content
- gellant
- water
- 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.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an aciclovir gel composition with improved performance. The aciclovir gel composition mainly includes aciclovir, sodium stearate and/or sodium palmitate, calcium acetate, pregelatinized starch, carbomer, a water miscible solvent and water. The gel composition has relatively high stability, and especially has relatively high salt tolerance, relatively high biological adhesion, and higher clinical effect.
Description
Technical field
The present invention relates to a kind of gel combination of performance improvement.Specifically, relate to a kind of gel combination of acyclovir of performance improvement.
Background technology
Acyclovir can be used as local topical medicine, is used for the treatment of herpes simplex or herpes zoster and infects, and existing its gel preparation is commercially available.Its main component is as follows: every gram of this product is containing 10 milligrams of acyclovirs, and adjuvant is: carbomer, triethanolamine, glycerol, ethyl hydroxybenzoate, disodium edetate, ethanol, sodium hydroxide, water for injection.
Unfortunately, often there is more transudate in herpes simplex or herpes zoster the infected affected part, in transudate, contain a certain amount of salinity, after transudate mixes with gel, salinity can make gel strength change (decline) by salting out, even there is precipitation, and can affect further the bioadhesive of carbomer, thereby affect its clinical efficacy.
In addition, in actual application, we are stable not after inventing that this gel preparation is long-term and placing, and as the change that viscosity is significantly spent, even occur precipitation or muddy etc.
Therefore, reality needs a kind of gel combination of acyclovir of performance improvement.
Summary of the invention
Through finding that we can provide a kind of gel combination of acyclovir of performance improvement.
The Aciclovir Gel compositions of performance improvement provided by the invention, mainly comprises main gellant, doubles as auxiliary gellant, bioadhesive material, a kind of water-miscible solvent and the water of stabilizing agent.This glue composition has higher stability, particularly higher salt tolerance and higher bioadhesive, thus there is higher clinical effect.
Detailed description of the invention
Compositions of the present invention comprises main gellant and auxiliary gellant.
In the present invention, main gellant used is at least one and the calcium acetate in sodium stearate, brown eleostearic acid sodium.Except calcium acetate, described solvent, water and described gellant need to be heated to high temperature and for example seethe with excitement, then obtained mixture is let cool to room temperature to carry out gelling.But unexpectedly, have now found that described solvent can at room temperature use calcium acetate gelling.This main gellant has higher salt tolerance and temperature stability.
Suitable auxiliary gellant is selected from pregelatinized Starch, and it also has higher salt tolerance and temperature stability.This auxiliary gellant is also expected to improve durability and the service life of gel combination forming, further to extend the time of contact of itself and skin.
Bioadhesive material used in the present invention is selected from carbomer, after neutralization, also makes gellant, further to extend the time of contact of itself and skin.
Above-mentioned three kinds of gellant can synergistic function, makes glue composition have particularly higher salt tolerance and higher bioadhesive of higher stability, thereby can improve the clinical effect of medicine.
By the gross weight of said composition, the amount of the main gellant (at least one in sodium stearate, brown eleostearic acid sodium and calcium acetate) using in the present composition respectively can be in the scope of approximately 0.5 % by weight-Yue 5 % by weight, more suitable is in approximately 1 % by weight-Yue 4 % by weight, the amount ratio of the two (at least one in sodium stearate, brown eleostearic acid sodium and calcium acetate) (mole) about 4:1 to 1:2, preferably 2:1.
By the gross weight of said composition, the amount of the auxiliary gellant (pregelatinized Starch) using in the present composition can be in the scope of approximately 0.5 % by weight-Yue 10 % by weight, more suitable is in approximately 1 % by weight-Yue 7 % by weight, more preferably be in approximately 1 % by weight-Yue 5 % by weight.
By the gross weight of said composition, the amount of the bioadhesive material carbomer using in the present composition respectively can be in the scope of approximately 0.5 % by weight-Yue 5 % by weight, and more suitable is in approximately 1 % by weight-Yue 3 % by weight,
Compositions of the present invention also comprises water.Wherein the source of water is not key.Suitable source comprises tap water, deionized water etc.But the viscosity of the present composition can be subject to the impact of water intermediate ion, therefore preferred deionized water.
By the gross weight of said composition, in the present composition, the amount of water is in the scope of approximately 25 % by weight-Yue 65 % by weight, and more suitable is in the scope of approximately 40 % by weight-Yue 60 % by weight.
By the gross weight of said composition, the amount of the principal agent acyclovir using in the present composition can be in the scope of approximately 0.05 % by weight-Yue 5 % by weight, more suitable is in approximately 0.1 % by weight-Yue 2.5 % by weight, more preferably be in approximately 0.5 % by weight-Yue 2 % by weight.
In compositions of the present invention, also comprise a kind of water-miscible solvent.Applicable water-miscible solvent includes but not limited to that alcohol is as ethanol, isopropyl alcohol etc.; Polyhydric alcohol (glycols) is as propylene glycol, dipropylene glycol, glycerol etc.; Water miscibility ester is as three acetic acid-glycerol etc.; Mean molecule quantity is not higher than 600 Polyethylene Glycol; And their mixture.In enforcement of the present invention, preferably use mean molecule quantity not higher than 600 Polyethylene Glycol, ethanol, glycerol and their mixture as water-miscible solvent; Particularly preferably preferably use mean molecule quantity not higher than 600 Polyethylene Glycol.By the gross weight of said composition, the amount of water-miscible solvent can be in the scope of approximately 10 % by weight-Yue 65 % by weight, and more suitable is in the scope of approximately 30 % by weight-Yue 50 % by weight.
The present invention can regulate with thickening agent the viscosity of compositions.Applicable thickening agent includes but not limited to carboxymethyl cellulose, methylcellulose, hydroxyethyl-cellulose and cuts quick property polysaccharide gum as xanthan gum, guar gum, karaya etc.By the gross weight of said composition, the amount of added thickening agent is in the scope of 0.001 % by weight-Yue 1 % by weight, more suitable in the scope of approximately 0.01 % by weight-Yue 0. 5 % by weight.
In compositions of the present invention, also comprise softening agent.Applicable softening agent includes but not limited to glycerol, propylene glycol, hexanediol, butanediol, dipropylene glycol and their mixture.By the gross weight of said composition, the addition of described softening agent is in the scope of 1 % by weight-Yue 10 % by weight, more suitable in the scope of approximately 2 % by weight-Yue 8 % by weight.
In compositions of the present invention, can comprise pH value regulator, as triethanolamine, sodium acetate, sodium hydroxide etc.
Compositions of the present invention can be non-antiseptical (providing with single dose form), or can be antiseptical.As known in the art, can use the antiseptic of effective dose as benzalkonium chloride, PHMB, sorbic acid, benzylalcohol, phenyl phenol etc.
In compositions of the present invention, also can comprise metal chelating agent, as disodium edetate, EDTA-Na.
By mixing required composition and stir until evenly prepare compositions of the present invention in applicable container.
[embodiment]
Embodiment 1
| Composition | Consumption (% by weight) |
| Acyclovir | 1 |
| Sodium stearate | 1.5 |
| Calcium acetate | 0.5 |
| Pregelatinized Starch | 2 |
| Carbomer | 2 |
| Ethanol | 40 |
| PEG 600 | 5 |
| Triethanolamine | 0.6 |
| Sodium hydroxide or acetic acid (regulating pH value 6-7.5) | In right amount |
| Water (adding to total amount 100) | In right amount |
| Altogether | 100 |
Embodiment 2
| Composition | Consumption (% by weight) |
| Acyclovir | 2 |
| Palm fibre eleostearic acid sodium | 2 |
| Calcium acetate | 1.5 |
| Pregelatinized Starch | 1 |
| Carbomer | 2 |
| Ethanol | 25 |
| PEG 400 | 10 |
| Triethanolamine | 0.6 |
| Sodium hydroxide or acetic acid (regulating pH value 6-7.5) | In right amount |
| Water (adding to total amount 100) | In right amount |
| Altogether | 100 |
Embodiment 3
| Composition | Consumption (% by weight) |
| Acyclovir | 1 |
| Sodium stearate | 1 |
| Calcium acetate | 0.5 |
| Pregelatinized Starch | 2 |
| Carbomer | 2 |
| Ethanol | 35 |
| Glycerol | 5 |
| Triethanolamine | 0.6 |
| Sodium hydroxide or acetic acid (regulating pH value 6-7.5) | In right amount |
| Water (adding to total amount 100) | In right amount |
| Altogether | 100 |
Preparation method:
The disperse system of above-mentioned sample is to prepare in the rustless steel container that agitator is housed.Carbomer is added in water and vigorous stirring, in water, form dispersed system, then add and slowly add principal agent and make it to be uniformly dispersed, then add sodium stearate, pregelatinized Starch and make it to be uniformly dispersed, after mixing, add again ethanol, glycerol (or PEG), calcium acetate and triethanolamine, mix, with sodium hydroxide or second acid for adjusting pH value 6-7.5, finally add water to enough (100%), stir until obtain a uniform disperse system.
Reference examples preparation method:
Pregelatinized Starch composition in above-described embodiment is removed, and other are all constant, prepare its reference examples (1-3) respectively by embodiment.
Stability test
Sample is placed at 40 DEG C and stores 6 months, and checks its physical stability after 1,2,3,4,5,6 month.If there is being separated, just think that sample is unstable.If do not occur being separated, then this sample is carried out to the test of freeze-thaw stability.Sample is frozen and melts three times therebetween.If being separated does not appear in sample in the time being returned to room temperature, just think that sample is stable, not so, just think that sample is unstable.Test result is as follows,
Table 1 sample stability test result
| ? | 0 month | January | February | March | April | May | June |
| Embodiment 1 | － | － | － | － | － | － | － |
| Reference examples 1 | － | － | － | － | ＋ | ＋ | ＋ |
| Embodiment 2 | － | － | － | － | － | － | － |
| Reference examples 2 | － | － | － | － | ＋ | ＋ | ＋ |
| Embodiment 3 | － | － | － | － | － | － | － |
| Reference examples 3 | － | － | － | － | ＋ | ＋ | ＋ |
| Commercially available sample | － | － | - | ＋ | ＋ | ＋ | ＋ |
Illustrate: "-" represents not perceive to be separated, and sample is stable; "+" represents to discover to be separated, and sample is unstable.
Result demonstration, embodiment sample has better stability.
Salt tolerance test
Sample thief 10g, slowly drips 20% sodium chloride solution to it, until muddy or be deposited in 30 minutes by jolting and can not disperse to disappear for extremely, record dropping sodium chloride solution volume number.
Table 2 gel combination salt tolerance test result
| ? | Sodium chloride solution volume number (ml) |
| Embodiment 1 | 4.8 |
| Reference examples 1 | 3.3 |
| Embodiment 2 | 4.1 |
| Reference examples 2 | 2.7 |
| Embodiment 3 | 4.4 |
| Reference examples 3 | 2.9 |
| Commercially available sample | 1.8 |
Result demonstration, embodiment sample has better salt tolerance.
Clinical effect test
Get embodiment 1 sample and commercially available sample respectively to herpes simplex or herpes zoster the infected by the application method medication in commercially available sample description: local outer painting, every day 5～6 times, 7 days courses for the treatment of of herpes simplex, 14 days courses for the treatment of of herpes zoster.
The standard of curative effect evaluation: sings and symptoms score value declines >=95% for curing, and score value decline 60%-94% is effective, and 20%-59% is effective in score value decline, and score value decline <20% is invalid.
The results are shown in Table 3.
Table 3 clinical effect test result
| ? | Cure | Effective | Effectively | Invalid | Total effective rate |
| Embodiment 1 sample | 11 | 13 | 8 | 3 | 91.4%（35） |
| Commercially available sample | 7 | 8 | 6 | 11 | 65.6%（32） |
Result demonstration, embodiment sample has better clinical effect.
Claims (10)
1. the Aciclovir Gel compositions of a performance improvement, mainly comprise that content is the acyclovir of 0.05 % by weight-5 % by weight, content is the main gellant of 0.5 % by weight-5 % by weight, content is the auxiliary gellant of 0.5 % by weight-10 % by weight, content is the bioadhesive material of 0.5 % by weight-5 % by weight, a kind of content is that water-miscible solvent and the content of 10 % by weight-65 % by weight is the water of 25 % by weight-65 % by weight, above-mentioned main gellant is selected from sodium stearate, at least one in palm fibre eleostearic acid sodium and calcium acetate, above-mentioned auxiliary gellant is selected from pregelatinized Starch, above-mentioned bioadhesive material is selected from carbomer, above-mentioned content is by the gross weight of said composition.
2. according to the compositions of claim 1, it is characterized by described water-miscible solvent and be selected from ethanol, glycerol, mean molecule quantity not higher than 600 Polyethylene Glycol, and their mixture.
3. according to the compositions of claim 1, it is characterized by described water-miscible solvent and be selected from mean molecule quantity not higher than 600 Polyethylene Glycol.
4. according to the compositions of claim 1, it is characterized by the gross weight by described compositions, the content of described water-miscible solvent is 30 % by weight-50 % by weight.
5. according to the compositions of claim 1, it is characterized by the gross weight by described compositions, the content of described main gellant is 1-4 % by weight.
6. according to the compositions of claim 1, it is characterized by sodium stearate in described main gellant and/or the consumption mol ratio of brown eleostearic acid sodium and calcium acetate is 4:1 to 1:2.
7. according to the compositions of claim 1, it is characterized by sodium stearate in described main gellant and/or the consumption mol ratio of brown eleostearic acid sodium and calcium acetate is 2:1.
8. according to the compositions of claim 1, it is characterized by the gross weight by described compositions, the content of described auxiliary gellant is 1 % by weight-5 % by weight.
9. according to the compositions of claim 1, it is characterized by the gross weight by described compositions, the content of described bioadhesive material is 1 % by weight-3 % by weight.
10. according to the compositions of claim 1, it is characterized by the gross weight by described compositions, the content of acyclovir is 0.1 % by weight-2.5 % by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410184833.8A CN103989626B (en) | 2014-05-05 | 2014-05-05 | A kind of Aciclovir Gel composition of performance improvement |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410184833.8A CN103989626B (en) | 2014-05-05 | 2014-05-05 | A kind of Aciclovir Gel composition of performance improvement |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103989626A true CN103989626A (en) | 2014-08-20 |
| CN103989626B CN103989626B (en) | 2018-12-18 |
Family
ID=51304136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410184833.8A Active CN103989626B (en) | 2014-05-05 | 2014-05-05 | A kind of Aciclovir Gel composition of performance improvement |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103989626B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1543957A (en) * | 2003-11-28 | 2004-11-10 | 湖北丽益医药科技有限公司 | Penciclovir gelling agent and its prepartion |
| CN1579373A (en) * | 2003-08-06 | 2005-02-16 | 北京扬新科技有限公司 | Transparent disappearing external administration carrier |
-
2014
- 2014-05-05 CN CN201410184833.8A patent/CN103989626B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1579373A (en) * | 2003-08-06 | 2005-02-16 | 北京扬新科技有限公司 | Transparent disappearing external administration carrier |
| CN1543957A (en) * | 2003-11-28 | 2004-11-10 | 湖北丽益医药科技有限公司 | Penciclovir gelling agent and its prepartion |
Non-Patent Citations (2)
| Title |
|---|
| 刘程等: "《表面活性剂性质理论与应用》", 30 June 2003, 北京工业大学出版社 * |
| 罗明生等: "《药剂辅料大全》", 31 January 2006, 四川科学技术出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103989626B (en) | 2018-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2009004475A (en) | Compositions comprising acid labile proton pump inhibiting agents, at least one other pharmaceutically active agent and methods of using same. | |
| WO2009100181A3 (en) | Absorbent ingestible agents and associated methods of manufacture and use | |
| JP2020196745A (en) | Topical composition containing ranpirnase | |
| JP2015537004A (en) | Stable thermolysin hydrogel | |
| KR20060108628A (en) | Water-based composition undergoing reversible thermogelation | |
| CN101472560A (en) | Pharmaceutical composition for treating burns (variants) and a method for the production thereof (variants) | |
| MX2010012933A (en) | Pharmaceutical compositions containing a fluoroquinolone antibiotic drug. | |
| CN103989626A (en) | Aciclovir gel composition with improved performance | |
| WO2014074995A1 (en) | Enema composition for treatment of ulcerative colitis having long term stability | |
| HK1123986A1 (en) | Pharmaceutical formulation for the treatment of osteoarthritis containing clodronic acid and hyaluronic acid | |
| CN112656939B (en) | Pharmaceutical composition of humanized antibody for vascular endothelial growth factor | |
| EP3049123B1 (en) | Catheter locking formulation and method to prepare same | |
| EP0012495A1 (en) | Pharmaceutical composition comprising a water soluble salt of amoxycillin and polyvinylpyrrolidone, and a vial containing a unit dose of said composition | |
| CN106389359B (en) | His pharmaceutical composition of the Baily department of injection and preparation method thereof | |
| JPH075456B2 (en) | Eye drops | |
| KR102295585B1 (en) | New Mineral Injection Composition | |
| JP2020011903A (en) | External composition | |
| CN1724567B (en) | Stable recombination human interferon alpha 1b water solution | |
| CN105263499B (en) | The combination of RO5503781, capecitabine and oxaliplatin use for cancer treatment | |
| CN109498632B (en) | Compound sulfamonomethoxine microcapsule preparation and preparation method thereof | |
| CN108367026A (en) | Antimicrobial preparation | |
| CN101152174A (en) | Stable rifamycin sodium injection prescription and preparing method of the same | |
| CN102204884B (en) | Composition preparation of ofloxacin compound and mannitol, and preparation method thereof | |
| EP0008905B1 (en) | Pharmaceutical compositions containing two beta-lactam derivatives | |
| JPH0477425A (en) | Indomethacin-containing formulation for external use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 214000, 35, Jing Xin Road, tin Beizhen Industrial Park, Xishan District, Jiangsu, Wuxi Applicant after: JIANGSU ZEYUN PHARMACEUTICAL CO., LTD. Address before: 214111 Jiangsu city of Wuxi Province town square Xinming Road No. 29 Applicant before: Jiangsu Sempoll Pharmaceutical Co., Ltd. |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: JIANGSU SHENGBAOLUO MEDICINE INDUSTRY CO., LTD. TO: JIANGSU ZHIYUAN PHARMACEUTICAL CO., LTD. |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder |
Address after: No. 35, Jingxin Road, industrial park, Xibei Town, Xishan District, Wuxi City, Jiangsu Province, 214000 Patentee after: Jiangsu Zhiyuan Pharmaceutical Co.,Ltd. Address before: No. 35, Jingxin Road, industrial park, Xibei Town, Xishan District, Wuxi City, Jiangsu Province, 214000 Patentee before: JIANGSU ZHIYUAN PHARMACEUTICAL Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder |