CN105147595A - Pemirolast potassium temperature sensitive hydrogel and preparation method thereof - Google Patents
Pemirolast potassium temperature sensitive hydrogel and preparation method thereof Download PDFInfo
- Publication number
- CN105147595A CN105147595A CN201510507221.2A CN201510507221A CN105147595A CN 105147595 A CN105147595 A CN 105147595A CN 201510507221 A CN201510507221 A CN 201510507221A CN 105147595 A CN105147595 A CN 105147595A
- Authority
- CN
- China
- Prior art keywords
- temperature sensitive
- concentration
- pemirolast potassiu
- sensitive hydrogel
- pluronics
- 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
- Medicinal Preparation (AREA)
Abstract
The invention relates to pemirolast potassium temperature sensitive hydrogel and a preparation method thereof. The pemirolast potassium temperature sensitive hydrogel is an aqueous solution which is mainly composed of pemirolast potassium, poloxamer 407, poloxamer 188 and an osmotic pressure adjustor, and is in the liquid state under temperature of 20-27 DEG C, and is an eye-drops preparation widely used for treating allergic conjunctivitis and vernal conjunctivitis. The pemirolast potassium temperature sensitive hydrogel is liquid under the room temperature, forms the semi-solid gel state after being dripped into eyes, and is adhered on the surfaces of the cornea and the cornea, so that the drug release is delayed, therefore, the problems of short retention time in the eyes and low bioavailability existing in the conventional eye drops are solved, the defects of the common ophthalmic gel preparation that the spreadability is poor and the dosage is difficult to control are overcome, and meanwhile, the irritation caused to the eyes by the dosage forms such as cream is also avoided.
Description
Technical field
The present invention relates to medicinal temperature sensitive hydrogel, be specifically related to a kind of Pemirolast Potassiu temperature sensitive hydrogel and preparation method thereof.
Background technology
Pemirolast Potassiu (English name: Pemirolastpotassium; Chemical name: 9-methyl-3-(1H-TETRAZOLE-5-base)-4H-pyrido [1,2-a] pyrimidin-4-one potassium salt) be a kind of mastocyte membrane stabilizer, effectively can suppress the release of the inflammatory mediator such as histamine, leukotriene.1977, Pemirolast Potassiu was developed as oral antasthmatic by Shi Guibao company of the U.S..1999, U.S. FDA approval pemirolast potassiumeye drops (trade name: Alamast) listing.Pemirolast potassiumeye drops is widely used in the treatment of anaphylaxis conjunctivitis and vernal conjunctivitis clinically.
At present, Pemirolast Potassiu drips ophthalmic preparation and is eye drop.Due to reasons such as nictation and ocular movements, the conventional eye drop solutions eye holdup time is short, bioavailability is lower." temperature-sensitive gel preparation " be a class with after solution state administration, can undergo phase transition immediately in the change of agents area along with temperature, be the preparation of semi-solid gel by liquid conversion.Such as, ophthalmic temperature sensitivity gel is at room temperature solution state, in liquid form in conjunctival sac after administration, can undergo phase transition within the eye in time, forms semi-solid gel.
At present, still not about the report of Pemirolast Potassiu temperature sensitive hydrogel.
Summary of the invention
For the deficiencies in the prior art, an object of the present invention is to provide a kind of ophthalmic preparation Pemirolast Potassiu temperature sensitive hydrogel being widely used in treatment anaphylaxis conjunctivitis and vernal conjunctivitis; Another object of the present invention is to provide the preparation method of above-mentioned Pemirolast Potassiu temperature sensitive hydrogel.
Pemirolast Potassiu temperature sensitive hydrogel of the present invention, be the aqueous solution be in a liquid state at 20-27 DEG C primarily of Pemirolast Potassiu, poloxamer188, PLURONICS F87 and osmotic pressure regulator composition, described each concentration of component is:
And the concentration ratio <3.7 of 3< poloxamer188 and PLURONICS F87.
In described Pemirolast Potassiu temperature sensitive hydrogel, the concentration of principal agent Pemirolast Potassiu is preferably 0.0009-0.002g/ml.
Poloxamer188 and PLURONICS F87, as pharmaceutical carrier, are the important adjuvants of described thermosensitive hydrogel preparation, affect its phase transition temperature, and then affect the rate of release of Pemirolast Potassiu in medication environment.Wherein, the concentration of poloxamer188 is preferably 0.15-0.30g/ml, is more preferably 0.19-0.21g/ml; The concentration of PLURONICS F87 is preferably 0.04-0.10g/ml, is more preferably 0.05-0.07g/ml.And the concentration ratio <3.7 of 3< poloxamer188 and PLURONICS F87, preferably, the concentration ratio <3.5 of 3.1< poloxamer188 and PLURONICS F87, more preferably, the concentration ratio <3.4 of 3.2< poloxamer188 and PLURONICS F87.
In the present invention, the ratio of the concentration of poloxamer188 and the concentration of PLURONICS F87 is extremely important, and when concentration ratio≤3 of poloxamer188 and PLURONICS F87, described thermosensitive hydrogel preparation does not produce gelling in temperature higher than when 27 DEG C; When concentration ratio >=3.7 of poloxamer188 and PLURONICS F87, namely described thermosensitive hydrogel preparation at room temperature produces phase transformation and is frozen into gel, does not meet formulation requirements.
In described Pemirolast Potassiu temperature sensitive hydrogel, adding of osmotic pressure regulator makes described hydrogel and tear have identical or higher osmotic pressure.Cross hyperosmotic solution owing to absorbing moisture, ocular tissue dewatered, dry and produce uncomfortable sensation; Hypisotonic solution then can make cornea tissue expand and cause pain.The described regulator that oozes can be selected from sodium chloride, glucose, glycerol, Polyethylene Glycol, propylene glycol.The concentration of described osmotic pressure regulator is 0.005-0.1g/ml, is preferably 0.01-0.08g/ml, is more preferably 0.04-0.06g/ml.
The pH value of Pemirolast Potassiu temperature sensitive hydrogel of the present invention is 6-8.
Pemirolast Potassiu temperature sensitive hydrogel of the present invention also can comprise other pharmaceutic adjuvants, as antiseptic, wetting agent and/or buffer agent.These pharmaceutic adjuvants, not to the essential characteristics of Pemirolast Potassiu temperature sensitive hydrogel, as phase transition temperature, have an impact.Other pharmaceutic adjuvants described can be selected from the adjuvant that can be used for ophthalmic preparation well known in the art.Such as, antiseptic can be selected from quaternary ammonium salt, as benzalkonium chloride, benzalkonium bromide; Cationic surfactant; Alcohols, as benzyl alcohol, chlorobutanol; Esters, oxybenzene ester; Sorbic acid (potassium) etc., preferred quaternary ammonium salt.Wetting agent can be selected from glycerol, ethanol, propylene glycol etc.; Buffer can be selected from phosphate buffer, borate buffer solution.The concentration of these pharmaceutic adjuvants is not particularly limited, acts on accordingly as long as its content can make it play.
In a specific embodiment, Pemirolast Potassiu temperature sensitive hydrogel of the present invention also comprises antiseptic, and the concentration of antiseptic is 0.0001-0.02ml/ml, is more preferably 0.0002-0.0005ml/ml.
In a preferred embodiment, Pemirolast Potassiu temperature sensitive hydrogel of the present invention comprises Pemirolast Potassiu, poloxamer188, PLURONICS F87, mannitol and benzalkonium bromide, and the concentration of each component is
Pemirolast Potassiu: 0.0009-0.002g/ml
Mannitol: 0.01-0.08g/ml
Poloxamer188: 0.19-0.21g/ml
PLURONICS F87: 0.05-0.07g/ml
Benzalkonium bromide: 0.0002-0.0005ml/ml
And the concentration <3.4 of the concentration/PLURONICS F87 of 3.2< poloxamer188.
In a most preferred embodiment, Pemirolast Potassiu temperature sensitive hydrogel of the present invention comprises
Pemirolast Potassiu: 0.001g/ml
Mannitol: 0.05g/ml
Poloxamer188: 0.20g/ml
PLURONICS F87: 0.06g/ml
Benzalkonium bromide: 0.0003ml/ml.
The preparation method of Pemirolast Potassiu temperature sensitive hydrogel of the present invention, comprises the following steps:
(1) Pemirolast Potassiu, poloxamer188, PLURONICS F87 and osmotic pressure regulator are added in distilled water, stir, for subsequent use;
(2) by swelling at 4-10 DEG C for the solution obtained in step (1), until obtain the solution of clear.
Wherein
In step (1), what add together with osmotic pressure regulator with Pemirolast Potassiu, poloxamer188, PLURONICS F87 can also have other pharmaceutic adjuvants, such as antiseptic, wetting agent and/or buffer agent.Each pharmaceutic adjuvant addition sequence is each other not particularly limited.
Pemirolast Potassiu temperature sensitive hydrogel of the present invention can be used as ophthalmic preparation.This Pemirolast Potassiu temperature sensitive hydrogel is at room temperature liquid, namely semi-solid gel state is formed in instillation eye, it adheres to Cornea and conjunctiva capsule surface, delay drug release, not only can solve the problem that the conventional eye drop solutions eye holdup time is short, bioavailability is not high, also overcome that common eye-gel preparation spreadability is poor, the uppity problem of dosage, the Ocular irritation using the dosage forms such as emulsifiable paste to cause can be avoided simultaneously.
Accompanying drawing explanation
Fig. 1 is according to the accumulative figure of the vitro release of the Pemirolast Potassiu temperature sensitive hydrogel of embodiment 4 preparation.
Detailed description of the invention
In order to understand the present invention further, below in conjunction with specific embodiment, the present invention is described in detail, should be understood that following embodiment is intended to illustrate, be not construed as limiting the present invention.
Test the instrument and material that adopt:
FA2004 electronic analytical balance (Shanghai Shun Yuhengping instrument company, 200g/0.1mg); UV-160A type ultraviolet spectrophotometer (Japanese Shimadzu Corporation); TS-200B type constant-temperature table (Changzhou Nuo Ji Instrument Ltd.);
Pemirolast Potassiu (Lunan Beite Pharmaceutical Co., Ltd.; Lot number: 140101, detect through HPLC, purity is 99.9%); Poloxamer188 (BASF Corp. of Germany, lot number: WPNI566B); PLURONICS F87 (BASF Corp. of Germany, lot number: WPHC625E); Other reagent are analytical pure.
List of references:
Document (Zhang Jianqiang, Yang Fang, Yao Jie, Deng. the development [J] of ciprofloxacin lactate instant gel for eye. Chinese antibiotic magazine, 2010,35 (4): 292-313) report, often dripping solution-type ophthalmic preparation volume averaging is 40 μ L, and in conjunctival sac, the volume of tear is 7 μ L.Temperature sensitive hydrogel is added dropwise to after in conjunctival sac and just forms gel with the mixed process of tear between diluting without tear and form gel more between the two after first mixing completely with tear.Therefore, suitable temperature sensitive hydrogel, at room temperature should be liquid condition, still can produce gelling in the temperature being less than 35 DEG C (in conjunctival sac temperature) after mixing completely with simulation tear 40:7 (V/V).The composition of simulation artificial tears used in following examples: comprise 2.18g sodium bicarbonate, 6.78g sodium chloride, 0.084g calcium chloride dihydrate and 1.38g potassium chloride.
Indicate:
Described Pemirolast Potassiu temperature sensitive hydrogel is at >27 DEG C and <35 DEG C temperature spot becomes semisolid from liquid state, form gel, described temperature spot is the phase transition temperature (also referred to as gelation temperature) of Pemirolast Potassiu temperature sensitive hydrogel.In the present invention, ambient temperature when " phase transition temperature " refers to described Pemirolast Potassiu temperature sensitive hydrogel complete gelation.
" room temperature " described in the present invention in the whole text refers to 10 DEG C-30 DEG C.
" concentration " of each component of Pemirolast Potassiu temperature sensitive hydrogel that the present invention is described in the whole text refers to that (for solids fraction in mass, unit is g for the amount of each component; For liquid composition by volume, unit is ml) with the ratio of volume (ml) of Pemirolast Potassiu temperature sensitive hydrogel aqueous solution under room temperature.
Preparation embodiment 1
Precision takes 0.1g Pemirolast Potassiu crude drug, 20g poloxamer188,6g PLURONICS F87 are put in conical flask, add 5% (g/ml) Osmitrol to 100ml, within after agitation as appropriate swelling 24 hours at 4 DEG C, namely obtain Pemirolast Potassiu temperature sensitive hydrogel.
Measure gelation temperature: take Pemirolast Potassiu temperature sensitive hydrogel 4ml obtained as stated above in test tube, medicinal liquid is all placed in below the water-bath water surface, with 1 DEG C of min
-1heating rate, constantly tilt test tube simultaneously, and the temperature when in vitro medicinal liquid no longer flows is gelation temperature (also referred to as phase transition temperature).In this embodiment, the gelation temperature of obtained Pemirolast Potassiu temperature sensitive hydrogel self is 28 DEG C; It is 34 DEG C when simulating with 0.7ml the gelation temperature recorded as stated above after artificial tears mixes.
Preparation embodiment 2
Precision takes 0.1g Pemirolast Potassiu crude drug, 18.6g poloxamer188,6g PLURONICS F87 are put in conical flask, add 5% (g/ml) Osmitrol to 100ml, within after agitation as appropriate swelling 20 hours at 4 DEG C, namely obtain Pemirolast Potassiu temperature sensitive hydrogel.
Gelation temperature measures with embodiment 1, and gelation temperature is 30.0 DEG C; It is 34.5 DEG C when simulating with 0.7ml the gelation temperature recorded as stated above after artificial tears mixes.
Preparation embodiment 3
Precision takes 0.2g Pemirolast Potassiu crude drug, 21g poloxamer188,6g PLURONICS F87 are put in conical flask, add 1% (g/ml) sodium-chloride water solution to 100ml, within after agitation as appropriate swelling 18 hours at 4 DEG C, namely obtain Pemirolast Potassiu temperature sensitive hydrogel.
Gelation temperature measures with embodiment 1, and gelation temperature is 27.2 DEG C; It is 30 DEG C when simulating with 0.7ml the gelation temperature recorded as stated above after artificial tears mixes.
Preparation embodiment 4
Precision takes 0.1g Pemirolast Potassiu crude drug, 20g poloxamer188,6g PLURONICS F87 are put in conical flask, add 0.03% (v/v) benzalkonium bromide aqueous solution, add 5% (g/ml) Osmitrol to 100ml, within after agitation as appropriate swelling 24 hours at 4 DEG C, namely obtain Pemirolast Potassiu temperature sensitive hydrogel.
Gelation temperature measures with embodiment 1, and gelation temperature is 28.5 DEG C; It is 34.0 DEG C when simulating with 0.7ml the gelation temperature recorded as stated above after artificial tears mixes.
Preparation embodiment 5
Precision takes 0.2g Pemirolast Potassiu crude drug, 16g poloxamer188,5g PLURONICS F87 are put in conical flask, add 0.03% (v/v) benzalkonium bromide aqueous solution, add 5% (g/ml) Osmitrol to 100ml, within after agitation as appropriate swelling 22 hours at 4 DEG C, namely obtain Pemirolast Potassiu temperature sensitive hydrogel.
Gelation temperature measures with embodiment 1, and gelation temperature is 30 DEG C; It is 34.9 DEG C when simulating with 0.7ml the gelation temperature recorded as stated above after artificial tears mixes.
Preparation embodiment 6
Precision takes 0.15g Pemirolast Potassiu crude drug, 23g poloxamer188,7g PLURONICS F87 are put in conical flask, add 0.02% (v/v) benzalkonium bromide aqueous solution, add 5% (g/ml) Osmitrol to 100ml, within after agitation as appropriate swelling 20 hours at 4 DEG C, namely obtain Pemirolast Potassiu temperature sensitive hydrogel.
Gelation temperature measures with embodiment 1, and gelation temperature is 27.1 DEG C; It is 28 DEG C when simulating with 0.7ml the gelation temperature recorded as stated above after artificial tears mixes.
Preparation embodiment 7
Precision takes 0.2g Pemirolast Potassiu crude drug, 20g poloxamer188,6g PLURONICS F87 are put in conical flask, add 0.03% (v/v) benzalkonium bromide aqueous solution, add 3% (g/ml) Osmitrol to 100ml, within after agitation as appropriate swelling 24 hours at 4 DEG C, namely obtain Pemirolast Potassiu temperature sensitive hydrogel.
Gelation temperature measures with embodiment 1, and gelation temperature is 28.7 DEG C; It is 34.3 DEG C when simulating with 0.7ml the gelation temperature recorded as stated above after artificial tears mixes.
Testing example 1
Vitro release is measured:
Tear in conjunctival sac is constantly updated, and the behavior such as rotation, nictation of eyes simultaneously all can affect the release of medicine.Without film stripping model (Zhang Jianqiang, Yang Fang, Yao Jie, Deng. the development [J] of ciprofloxacin lactate instant gel for eye. Chinese antibiotic magazine, 2010,35 (4): 292-313) selection is provided for studying the drug release occurred along with gel erosion, the method adopts simulation tear gel surface to be produced to the shear action of similar nictation under oscillating condition, the corrosion of water-soluable gel and drug release synchronously carry out, and meet instant gel for eye real processes in vivo.
4 DEG C time, eye thermosensitive hydrogel embodiment 4 prepared is about 4ml and joins in the test tube of having weighed in advance, this container is placed in the agitator preheating 5min of 35 DEG C, makes polymer be fully formed gel state.Add the artificial tears 2.4ml of preheating in advance as release medium, constant temperature oscillation 20min under the frequency of 75r/min, pour out whole release medium immediately, container surfaces externally and internally is blotted, rapid weighing record, be reentered into agitator inner equilibrium 5min, then supplement artificial tears and continue vibration 20min.Repeatable operation like this.Adopt under 357nm ultraviolet wavelength after the release medium poured out is diluted 10 times and measure absorbance A.
As shown in Figure 1, gel adds up corrosion amount and medicine Cumulative release amount returns the time respectively, and result is good linear relationship, meets zero order kinetics feature for result.Add up corrosion amount with the Cumulative release amount of medicine to gel to return, same in good linear relationship, drug release carries out with identical speed with the corrosion of gel, show that gel erosion is the principal element of limit drug release, this shows, be that semisolid gel can increase the time of staying of this medicine at eye by medicine phase inversion of the present invention, thus reach the effect of slow release
Testing example 2
Influence factor tests:
The Pemirolast Potassiu temperature sensitive hydrogel prepared according to embodiment 4 is loaded cillin bottle, be placed in light (natural light and illumination are under the daylight lamp condition of 4500Lx) respectively, high temperature (60 DEG C of calorstats) and low temperature (4 DEG C of refrigerators), place 10 days, respectively at sampling in the 0th, 5,10 day, investigate Pemirolast Potassiu temperature sensitive hydrogel content, gelation temperature.Result shows, and after each experiment investigation of influence factor, content and the gelation temperature of Pemirolast Potassiu temperature sensitive hydrogel of the present invention are all unchanged, and properties of samples is stable, reliable, and concrete outcome is in table 1.
Table 1. influence factor result of the test
| Condition | Time (d) | Gelation temperature (DEG C) | Content (%) |
| Natural light irradiation | 0 | 28.5℃ | 100.00％ |
| 5 | 28.5℃ | 100.12％ | |
| 10 | 28.5℃ | 100.19％ | |
| 4500Lx daylight lamp irradiates | 0 | 28.5℃ | 100.00％ |
| 5 | 28.5℃ | 100.03％ | |
| 10 | 28.5℃ | 100.02％ | |
| High temperature (60 DEG C of calorstats) | 0 | 28.5℃ | 100.00％ |
| 5 | 28.5℃ | 100.21％ | |
| 10 | 28.5℃ | 100.15％ | |
| Low temperature (4 DEG C of refrigerators) | 0 | 28.5℃ | 100.00％ |
| 5 | 28.5℃ | 99.97％ | |
| 10 | 28.5℃ | 100.01％ |
Although describe the present invention with reference to particular, those skilled in the art will recognize that, when not departing from purport of the present invention and scope, can change described embodiment or improve.
Claims (15)
1. a Pemirolast Potassiu temperature sensitive hydrogel, be the aqueous solution be in a liquid state at 20-27 DEG C primarily of Pemirolast Potassiu, poloxamer188, PLURONICS F87 and osmotic pressure regulator composition, described each concentration of component is:
And the concentration ratio <3.7 of 3< poloxamer188 and PLURONICS F87.
2. Pemirolast Potassiu temperature sensitive hydrogel according to claim 1, is characterized in that, described osmotic pressure regulator is selected from sodium chloride, glucose, glycerol, Polyethylene Glycol or propylene glycol.
3. Pemirolast Potassiu temperature sensitive hydrogel according to claim 1, is characterized in that, the concentration of described Pemirolast Potassiu is 0.0009-0.002g/ml.
4. the Pemirolast Potassiu temperature sensitive hydrogel according to claim 1 or 3, it is characterized in that, the concentration of described poloxamer188 is 0.15-0.30g/ml, the concentration of PLURONICS F87 is 0.04-0.10g/ml, and the concentration ratio <3.5 of 3.1< poloxamer188 and PLURONICS F87.
5. the Pemirolast Potassiu temperature sensitive hydrogel according to claim 1 or 3, it is characterized in that the concentration of described poloxamer188 is 0.19-0.21g/ml, the concentration of PLURONICS F87 is 0.05-0.07g/ml, and the concentration ratio <3.4 of 3.2< poloxamer188 and PLURONICS F87.
6. Pemirolast Potassiu temperature sensitive hydrogel according to claim 1, is characterized in that, the concentration of described osmotic pressure regulator is 0.01-0.08g/ml.
7. Pemirolast Potassiu temperature sensitive hydrogel according to claim 1, is characterized in that, the concentration of described osmotic pressure regulator is 0.03-0.05g/ml.
8. Pemirolast Potassiu temperature sensitive hydrogel according to claim 1, is characterized in that, also comprise antiseptic, and antiseptic is selected from benzalkonium chloride, benzalkonium bromide, cationic surfactant, benzyl alcohol, chlorobutanol or oxybenzene ester.
9. Pemirolast Potassiu temperature sensitive hydrogel according to claim 8, is characterized in that, the concentration of described antiseptic is 0.0001-0.02ml/ml.
10. Pemirolast Potassiu temperature sensitive hydrogel according to claim 8, is characterized in that, the concentration of described antiseptic is 0.0002-0.0005ml/ml.
11. Pemirolast Potassiu temperature sensitive hydrogels according to claim 1, is characterized in that, also comprise wetting agent and/or buffer agent, wetting agent is selected from glycerol, ethanol, propylene glycol; Buffer is selected from phosphate buffer, borate buffer solution.
12. 1 kinds of Pemirolast Potassiu temperature sensitive hydrogels, it is characterized in that being made up of Pemirolast Potassiu, poloxamer188, PLURONICS F87, mannitol and benzalkonium bromide, the concentration of each component is:
Pemirolast Potassiu: 0.0009-0.002g/ml
Mannitol: 0.04-0.06g/ml
Poloxamer188: 0.19-0.21g/ml
PLURONICS F87: 0.05-0.07g/ml
Benzalkonium bromide: 0.0002-0.0005ml/ml
And the concentration <3.4 of the concentration/PLURONICS F87 of 3.2< poloxamer188.
13. Pemirolast Potassiu temperature sensitive hydrogels according to claim 12, is characterized in that, the concentration of each component is:
Pemirolast Potassiu: 0.001g/ml
Mannitol: 0.05g/ml
Poloxamer188: 0.20g/ml
PLURONICS F87: 0.06g/ml
Benzalkonium bromide: 0.0003ml/ml.
The preparation method of 14. 1 kinds of Pemirolast Potassiu temperature sensitive hydrogels according to claim 1, comprises the following steps:
(1) Pemirolast Potassiu, poloxamer188, PLURONICS F87 and osmotic pressure regulator are added in distilled water, stir, for subsequent use;
(2) by swelling at 4-10 DEG C for the solution obtained in step (1), until obtain the solution of clear.
15. preparation methoies according to claim 14, also can add other pharmaceutic adjuvants in step (1), as antiseptic, wetting agent and/or buffer agent osmotic pressure regulator.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510507221.2A CN105147595B (en) | 2015-08-18 | 2015-08-18 | Pemirolast Potassiu temperature sensitive hydrogel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510507221.2A CN105147595B (en) | 2015-08-18 | 2015-08-18 | Pemirolast Potassiu temperature sensitive hydrogel and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105147595A true CN105147595A (en) | 2015-12-16 |
| CN105147595B CN105147595B (en) | 2018-08-31 |
Family
ID=54788891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510507221.2A Active CN105147595B (en) | 2015-08-18 | 2015-08-18 | Pemirolast Potassiu temperature sensitive hydrogel and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105147595B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107496442A (en) * | 2017-08-25 | 2017-12-22 | 南京斯泰尔医药科技有限公司 | A kind of chlorine dioxide responsive to temperature type spray gel and preparation method thereof |
| CN108721207A (en) * | 2017-04-19 | 2018-11-02 | 复旦大学 | Amination poloxamer derivative responsive to temperature type instant gelling agent and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009161454A (en) * | 2007-12-28 | 2009-07-23 | Lion Corp | Ophthalmic composition |
| CN101587106A (en) * | 2008-05-20 | 2009-11-25 | 张明智 | Content measurement method of pemirolast potassiumeye drops |
| CN101966143A (en) * | 2009-07-28 | 2011-02-09 | 胡容峰 | Preparation and application of gatifloxacin temperature and pH sensitive ophthalmic gel |
-
2015
- 2015-08-18 CN CN201510507221.2A patent/CN105147595B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009161454A (en) * | 2007-12-28 | 2009-07-23 | Lion Corp | Ophthalmic composition |
| CN101587106A (en) * | 2008-05-20 | 2009-11-25 | 张明智 | Content measurement method of pemirolast potassiumeye drops |
| CN101966143A (en) * | 2009-07-28 | 2011-02-09 | 胡容峰 | Preparation and application of gatifloxacin temperature and pH sensitive ophthalmic gel |
Non-Patent Citations (1)
| Title |
|---|
| 刘春亮: "HPLC法测定吡嘧司特钾滴眼液中苯扎溴铵和苯扎氯铵的含量", 《中国药事》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108721207A (en) * | 2017-04-19 | 2018-11-02 | 复旦大学 | Amination poloxamer derivative responsive to temperature type instant gelling agent and preparation method thereof |
| CN107496442A (en) * | 2017-08-25 | 2017-12-22 | 南京斯泰尔医药科技有限公司 | A kind of chlorine dioxide responsive to temperature type spray gel and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105147595B (en) | 2018-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kumar et al. | Modification of in situ gelling behavior of carbopol solutions by hydroxypropyl methylcellulose | |
| Patel et al. | Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability | |
| Gupta et al. | Ion-and pH-activated novel in-situ gel system for sustained ocular drug delivery | |
| Gupta et al. | Sustained ocular drug delivery from a temperature and pH triggered novel in situ gel system | |
| CN109310687B (en) | Aqueous composition containing atropine | |
| Coffey et al. | Development of a non-settling gel formulation of 0.5% loteprednol etabonate for anti-inflammatory use as an ophthalmic drop | |
| Saini et al. | In situ gels-a new trends in ophthalmic drug delivery systems | |
| Li et al. | A novel ion-activated in situ gelling ophthalmic delivery system based on κ-carrageenan for acyclovir | |
| HRP20050460A2 (en) | Methods of measuring the dissolution rate of an analyte in a non-aqueous liquid composition | |
| Mittal et al. | In situ gelling ophthalmic drug delivery system: Formulation and evaluation | |
| CN101757621A (en) | Cyclodextrin inclusion drug composition for ocular inflammation resistance | |
| CN105147595A (en) | Pemirolast potassium temperature sensitive hydrogel and preparation method thereof | |
| US20110082221A1 (en) | In situ gelling systems as sustained delivery for front of eye | |
| Saudagar et al. | Review on in-situ nasal gel drug delivery system | |
| Xu et al. | Preparation and characterization of ion-sensitive brimonidine tartrate in situ gel for ocular delivery | |
| Gupta et al. | Design and evaluation of thermoreversible in situ gelling system of forskolin for the treatment of glaucoma | |
| CN101966144A (en) | Preparation and application of olopatadine in-situ gel | |
| Zaki et al. | Ketorolac tromethamine in-situ ocular hydro gel; preparation, characterization, and in-vivo evaluation | |
| CN103239390B (en) | Tropicamide ophthalmic temperature-sensitive in-situ gel and preparation method thereof | |
| Pescina et al. | Mydriatics release from solid and semi-solid ophthalmic formulations using different in vitro methods | |
| CN101966143A (en) | Preparation and application of gatifloxacin temperature and pH sensitive ophthalmic gel | |
| CN104188894B (en) | Butenafine temperature-sensitive gel preparation and preparation method thereof | |
| KR20150100670A (en) | Topical ophthalmological pharmaceutical composition containing regorafenib | |
| CN100548273C (en) | Instant cordate houttuynia gel preparation for eye | |
| CN103040726B (en) | Novel ophthalmic curcumin multi-core vesicle gel preparation and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |