CN105902484A - Ganciclovir ophthalmic gel and preparation method thereof - Google Patents
Ganciclovir ophthalmic gel and preparation method thereof Download PDFInfo
- Publication number
- CN105902484A CN105902484A CN201610322109.6A CN201610322109A CN105902484A CN 105902484 A CN105902484 A CN 105902484A CN 201610322109 A CN201610322109 A CN 201610322109A CN 105902484 A CN105902484 A CN 105902484A
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- Prior art keywords
- ganciclovir
- gel
- ophthalmic gel
- preparation
- ganciclovir ophthalmic
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses ganciclovir ophthalmic gel, which is prepared from the following ingredients in proportion by weight: 0.1 to 0.2 percent of ganciclovir, 0.3 to 0.4 percent of Carbomer 934P, 4 to 6 percent of mannitol, 0.1 to 0.2 percent of sodium hydroxide, 0.1 to 0.2 percent of bromogeramine and the balance injection water. The invention also discloses a preparation method of the ganciclovir ophthalmic gel. The ganciclovir ophthalmic gel provided by the invention has the advantages that the sterile requirements of an ophthalmic preparation can be completely met; impurities of ganciclovir raw medicine in the preparation are lower; the stability is higher; higher safety and effectiveness are realized.
Description
Technical field
The invention belongs to technical field of medicine, be specifically related to a kind of ganciclovir ophthalmic gel and preparation method thereof.
Background technology
Ganciclovir is the analog of a kind of 2 ＇-deoxyguanytic acid, can suppress the duplication of herpesvirus.Clinic is
Confirming, ganciclovir is effective to the infection caused by cytomegalovirus (CMV) and herpes simplex virus (HSV).More former times
Lip river Wei ophthalmic preparation is the choice drug for the treatment of HSK.
Traditional ophthalmic preparation includes eye drop and eye ointment.The subject matter that eye drop exists is that bioavailability is relatively low, about
The active medicine of 95% can run off, and drug effect remains short, is administered frequently, and dosage is not easy to control, and due to night
It is administered inconvenience so that pharmacology peak valley phenomenon highlights；And the substrate in the semi-solid preparation such as ointment, ointment is transparent because of it
Degree and the factor of index of refraction, easily cause the visual field and obscure, make troubles to patient medication.
Eye-gel preparation, through selecting suitable excipient, is made transparent semi-solid ophthalmic preparation, can be avoided both the above
The shortcoming of dosage form.But owing to gel is semi-solid preparation, it is impossible to filtration sterilization；And because its thermal break-through power is the lowest, the most not
The pressure sterilizing technique preferably using routine carries out terminal sterilization；Irradiation sterilization produces impact to the stereochemical structure of gel-type vehicle,
And then the stickiness of change gel, affect the curative effect of gel.Therefore, prior art is difficult to produce aseptic level and conforms to
The product asked, brings potential safety hazard to the Clinical practice of gel for eye use.
Summary of the invention
For the deficiencies in the prior art, it is an object of the invention to provide a kind of ganciclovir ophthalmic gel, this eye
Having suitable viscosity with gel, higher aseptic level and well quality stability, it is ophthalmically acceptable that the present invention also provides for this
The preparation method of gel.
The above-mentioned purpose of the present invention is achieved through the following technical solutions:
A kind of ganciclovir ophthalmic gel, it is grouped into by the one-tenth of following weight proportion:
Preferably, described ganciclovir ophthalmic gel is grouped into by the one-tenth of following weight proportion:
Preparation method provided by the present invention comprises the following steps:
(1) card pool nurse 934P is inserted account for total amount 30～50% water for injection in swelling, until forming uniform gel,
Then proceed in autoclaving tank, under stirring, with 121 DEG C, 0.11MPa sterilizing 30 minutes, be cooled to 40～50 DEG C
Standby；
(2) after mannitol, sodium hydroxide, ganciclovir being dissolved with the water for injection accounting for total amount 40～60%, through 0.22 μm
The microporous filter membrane aseptic filtration in aperture, filtrate adds in (1), and stirring while adding, mixing speed maintains 40～50rpm；
(3) with the microporous filter membrane aseptic filtration in 0.22 μm aperture after bromo geramine being diluted with remaining water for injection, add
Enter in (2), stir 1～3 hour, to stirring, obtain ganciclovir ophthalmic gel；
(4) by prepared ganciclovir ophthalmic gel through sterile filling in ointment tube.
Compared with prior art, the beneficial effects of the present invention is:
The ganciclovir ophthalmic gel of gained of the present invention is aqueous solution type gel, fully meets ophthalmic preparation to aseptic guarantor
The requirement of card level；The every quality index of gel complies fully with the regulation of quality standard；Ganciclovir crude drug is in the formulation
Impurity lower, stability is more preferable；Ensure that the safety and efficacy of ganciclovir ophthalmic gel Clinical practice.Specifically
It is embodied in the following aspects:
(1) selecting the carbomer of appropriate size and suitable concentration, prepared gel viscosity is in 50～100cpa s scopes
In, in this viscosity scope, just make gel have the suitable holdup time in aqueous humor, not only ensure that the absorption of medicine,
Ensure that medicine will not flow into nasal cavity through nasolacrimal duct and cause patient uncomfortable simultaneously；And this viscosity makes gel have certain flowing
Property, it is simple to patient's self-administer.
(2) sterilization method uses the mode that pressure sterilizing, filtration sterilization, sterile working combine, and product can be effectively ensured
The aseptic level of product.
(3) mode of associating sterilizing is compared with simple pressure sterilizing, it is to avoid the sterilizing that causes not because of thermal break-through power
Halfway risk；Compared with irradiation sterilization, the viscosity of gel will not change, it is ensured that the quality of gel.
(4) in preparation process, crude drug is without high temperature, and its impurity can ensure in the lowest level, it is ensured that
The safety of clinical application.
Detailed description of the invention
Following each embodiment is used for further illustrating the present invention.
Embodiment 1:
A kind of ganciclovir ophthalmic gel, its formula composition (w/w) is as follows:
The method step that the raw material of above-mentioned formula is prepared as ganciclovir ophthalmic gel is as follows:
(1) card pool nurse 934P is inserted account in the water for injection of total amount 40% swelling more than 12 hours, to being formed uniformly
Gel, in autoclaving tank, under stirring, temperature be 121 DEG C, pressure be 0.11MPa under the conditions of sterilizing 30
Minute, be cooled to subsequently 40～50 DEG C standby.
(2) after mannitol, sodium hydroxide, ganciclovir being dissolved with the water for injection accounting for total amount 50%, through 0.22 μm
The microporous filter membrane aseptic filtration in aperture, filtrate adds in (1), and stirring while adding, mixing speed maintains 40～50rpm.
(3) by the degerming mistake of microporous filter membrane in 0.22 μm aperture after bromo geramine being diluted with remaining 10% water for injection
Filter, adds in (2), stirs 2 hours, to stirring, obtain ganciclovir ophthalmic gel.
(4) by prepared ganciclovir ophthalmic gel through sterile filling in ointment tube, get product.
The gel prepared is transparent aqueous solution type gel, pH7.8, viscosity 76cpa s.
Reference examples 1:
A kind of ganciclovir ophthalmic gel, its formula composition is same as in Example 1.
Preparation method is:
(1) card pool nurse 934P is inserted account in the water for injection of total amount 40% swelling more than 12 hours, to being formed uniformly
Gel；After mannitol, sodium hydroxide, bromo geramine, ganciclovir being dissolved with the water for injection accounting for total 60%, add
Enter wherein, stirring while adding, to forming uniform gel.In autoclaving tank, under stirring, with 121 DEG C, 0.11MPa
To gel sterilizing 30 minutes, it is down to room temperature, obtains ganciclovir ophthalmic gel.
The gel prepared is transparent aqueous solution type gel, pH7.2, viscosity 68cpa s.
Reference examples 2:
A kind of ganciclovir ophthalmic gel, its formula composition is same as in Example 1.
Preparation method is:
(1) card pool nurse is inserted account in the water for injection of total amount 40% swelling more than 12 hours, to forming uniform gel；
After mannitol, sodium hydroxide, bromo geramine, ganciclovir being dissolved with remaining 60% water for injection, it is added thereto,
Stirring while adding, to forming uniform gel.
(2) by prepared ganciclovir ophthalmic gel through sterile filling in ointment tube.
(3) canned gel is through gamma-ray irradiation sterilizing.
The gel prepared is transparent aqueous solution type gel, pH7.6, viscosity 24cpa s.
The ganciclovir ophthalmic gel preparing above-described embodiment and reference examples is studied:
(1) toxicologic study
According to " Chemical induced irritation anaphylaxis and hemolytic investigative technique guideline ", to embodiment 1 and reference examples 1,
Reference examples 2 has carried out zest and anaphylaxis research, and result of study shows, embodiment 1, reference examples 1, reference examples 2
The most there is not pharmaceutical ocular zest；
(2) stability study
Each group sample be placed in 40 ± 2 DEG C, relative humidity be to observe 6 months, respectively at 1,2,3,6 under the conditions of 75 ± 5%
Sampling detection in individual month, the results are shown in Table 1.
Table 1 stability test result
Result shows: accelerated test 6 months, and the character of three groups of medicines, content do not have significant change, sterility test all to accord with
Close regulation；Reference examples 1 group has related substance apparently higher than embodiment 1 group and reference examples 2 groups, and has increase trend, shows
Ganciclovir ophthalmic gel is unsuitable for simple pressure sterilizing, and ganciclovir at high temperature has certain degraded；Reference examples
The viscosity of 2 groups is substantially less than embodiment 1 group and reference examples 1 group, and relatively low viscosity is unfavorable for medicine delay in aqueous humor
And drug absorption, show that irradiation sterilization creates considerable influence to the viscosity of ganciclovir ophthalmic gel.
Claims (3)
1. a ganciclovir ophthalmic gel, it is characterised in that be grouped into by the one-tenth of following weight proportion:
Ganciclovir ophthalmic gel the most according to claim 1, it is characterised in that by the composition of following weight proportion
Composition:
The preparation method of ganciclovir ophthalmic gel the most according to claim 1 and 2, it is characterised in that include with
Lower step:
(1) card pool nurse 934P is inserted account for total amount 30～50% water for injection in swelling, until forming uniform gel,
Then proceed in autoclaving tank, under stirring, with 121 DEG C, 0.11MPa sterilizing 30 minutes, be cooled to 40～50 DEG C
Standby；
(2) after mannitol, sodium hydroxide, ganciclovir being dissolved with the water for injection accounting for total amount 40～60%, through 0.22 μm
The microporous filter membrane aseptic filtration in aperture, filtrate adds in (1), and stirring while adding, mixing speed maintains 40～50rpm；
(3) with the microporous filter membrane aseptic filtration in 0.22 μm aperture after bromo geramine being diluted with remaining water for injection, add
Enter in (2), stir 1～3 hour, to stirring, obtain ganciclovir ophthalmic gel；
(4) by prepared ganciclovir ophthalmic gel sterile filling in ointment tube.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610322109.6A CN105902484A (en) | 2016-05-16 | 2016-05-16 | Ganciclovir ophthalmic gel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610322109.6A CN105902484A (en) | 2016-05-16 | 2016-05-16 | Ganciclovir ophthalmic gel and preparation method thereof |
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| Publication Number | Publication Date |
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| CN105902484A true CN105902484A (en) | 2016-08-31 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610322109.6A Pending CN105902484A (en) | 2016-05-16 | 2016-05-16 | Ganciclovir ophthalmic gel and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110801430A (en) * | 2019-09-19 | 2020-02-18 | 湖北科益药业股份有限公司 | Ganciclovir ophthalmic gel and preparation method thereof |
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|---|---|---|---|---|
| CN1868449A (en) * | 2006-06-14 | 2006-11-29 | 湖北科益药业股份有限公司 | Ganciclovir ophthalmic gel and its prepn. method |
| US20080286344A1 (en) * | 2007-05-16 | 2008-11-20 | Olivia Darmuzey | Solid form |
| US20080311162A1 (en) * | 2007-05-16 | 2008-12-18 | Olivia Darmuzey | Solid form |
| CN101342180A (en) * | 2008-08-21 | 2009-01-14 | 武汉远大制药集团有限公司 | Medicament composition for eyes and preparation method thereof |
| CN102764231A (en) * | 2012-08-10 | 2012-11-07 | 何群 | Ophthalmic gel for treating herpes simplex viral keratitis and preparation method of ophthalmic gel |
| CN104606682A (en) * | 2015-01-21 | 2015-05-13 | 温州医科大学 | Ganciclovir eye preparation and preparation method thereof |
-
2016
- 2016-05-16 CN CN201610322109.6A patent/CN105902484A/en active Pending
Patent Citations (6)
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| CN1868449A (en) * | 2006-06-14 | 2006-11-29 | 湖北科益药业股份有限公司 | Ganciclovir ophthalmic gel and its prepn. method |
| US20080286344A1 (en) * | 2007-05-16 | 2008-11-20 | Olivia Darmuzey | Solid form |
| US20080311162A1 (en) * | 2007-05-16 | 2008-12-18 | Olivia Darmuzey | Solid form |
| CN101342180A (en) * | 2008-08-21 | 2009-01-14 | 武汉远大制药集团有限公司 | Medicament composition for eyes and preparation method thereof |
| CN102764231A (en) * | 2012-08-10 | 2012-11-07 | 何群 | Ophthalmic gel for treating herpes simplex viral keratitis and preparation method of ophthalmic gel |
| CN104606682A (en) * | 2015-01-21 | 2015-05-13 | 温州医科大学 | Ganciclovir eye preparation and preparation method thereof |
Non-Patent Citations (2)
| Title |
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| KISHORE CHOLKAR: "《Ocular Pharmacology and Toxicology》", 30 August 2013 * |
| 刘潇潇: ""更昔洛韦眼用即型凝胶剂的制备及质量评价"", 《海峡药学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110801430A (en) * | 2019-09-19 | 2020-02-18 | 湖北科益药业股份有限公司 | Ganciclovir ophthalmic gel and preparation method thereof |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170322 Address after: 430205 East Lake New Technology Development Zone, Wuhan Province, the south of the Yellow Dragon Road, No. section of the benefits of Industrial Park, No. 8 Applicant after: Hubei Liyi Medicine Sci-Tech Co., Ltd. Applicant after: Hubei Keyi Pharmaceutic Co., Ltd. Address before: 430205 East Lake New Technology Development Zone, Wuhan Province, the south of the Yellow Dragon Road, No. section of the benefits of Industrial Park, No. 8 Applicant before: Hubei Liyi Medicine Sci-Tech Co., Ltd. |
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| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160831 |