CN1194664C - In-vivo gel preparatino able to be dropped in eyes and its preparing process - Google Patents
In-vivo gel preparatino able to be dropped in eyes and its preparing process Download PDFInfo
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- CN1194664C CN1194664C CNB021365806A CN02136580A CN1194664C CN 1194664 C CN1194664 C CN 1194664C CN B021365806 A CNB021365806 A CN B021365806A CN 02136580 A CN02136580 A CN 02136580A CN 1194664 C CN1194664 C CN 1194664C
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Abstract
The present invention relates to an in-vivo gel preparation dropped in eyes and a preparing process thereof. The gel preparation for eyes has a liquid state in vitro and has a gel state when the gel preparation for eyes is dropped in eyes. The gel preparation for eyes is prepared from an antibacterial antiphlogistic agent as an active substance, an auxiliary thickening agent, a preservative, an isoosmotic adjusting agent, a pH adjusting agent and water. The gel preparation for eyes is suitable for treating eye infection such as bacterial conjunctivitis, keratitis, corneal ulcer, dacryocystitis, postoperative infection, etc. The gel preparation for eyes has the liquid state in vitro and has the advantages of easy accurate control of dosages, and convenient operation. After being dropped in the eyes, the gel preparation for eyes is uniformly spread and forms gel; the gel preparation for eyes has long stay time in the eyes and is difficult to lose; the present invention maintains an effective medical concentration, strengthens a therapeutic effect, and has the advantages of low toxicity, small stimulation performance and good biocompatibility. The present invention is new effective medicine for eyes. The present invention can be applied clinically and has wide development prospects.
Description
Technical field
The present invention relates to the dropped in eyes preparation, especially be used in body gel preparation and preparation method thereof about a kind of dropped in eyes
Background technology
According to statistics, the patient 80%～90% that the ophthalmology outpatient service is gone to a doctor, ophthalmology infects, and eye inflammation generally is divided into non-infectious ophthalmia and infectious ophthalmia two big classes.Ophthalmology infects and comprises conjunctivitis, meibomitis, tarsitis, keratitis and global inflammation etc.; Comprise bacterial infection and fungal infection from the pathogen branch.Bacterial infection can use anti-infectives, but because the existence of blood a glance barrier, the concentration that medicine reaches some tissue of ophthalmic is restricted, and can not all penetrate.Therefore the anti-infective that is used for ophthalmology is the good anti-infectives of those permeabilitys, as tobramycin, lincomycin, gentamycin and chloromycetin etc.Quinolones increased rapidly in the application of ophthalmology in recent years, and principal item has ofloxacin, levofloxacin, norfloxacin and ciprofloxacin etc.Cephalosporins commonly used is because permeability difference and drug resistance problem and the less ophthalmology that is used for.The sickness rate of fungal infection has showed increased trend in recent years, but the ophthalmic medicine of anti-fungal infection is rarely found.
Current clinical anti-infectives commonly used occurs with conventional dosage forms such as eye drop, eye ointment mostly, eye drop is as the most frequently used topical dosage form of ophthalmology, after splashing into ophthalmic, can be diluted to 0.1% of original concentration by tear in several minutes, therefore needing increases the eye dripping frequency, for use brings a lot of inconvenience.Though the eye ointment release is slow since with vaseline as substrate, greasy feeling strong and use after affect one's power of vision and attractive in appearance, night, clothing was easily polluted in applications again, thereby patient's use of not too being willing to.This just impels people to carry out the development work of gel preparation, for example the Chinese patent CN1189773A of Germany's lid Hartmann chemical pharmacy company limited application is a kind of aseptic dropped in eyes gel preparation, it has a kind of water and a kind of hydrophobic biphase carrier liquid or gel base material mutually of containing, material is mainly polyacrylic acid or polymeric acrylic acid derivative and derivative of fatty acid, triglyceride and/or phthalic acid ester, mainly be to solve under condition without emulsifying agent, obtain a kind of interpolation active substance and homodisperse gel, but it mainly is to be used for artificial tears and processing " xerophthalmia ", but not the treatment ocular infection.Because of gel for eye use adopts aqueous matrix, excellent biological compatibility is arranged, zest is little, some advantages that not only have Eye ointments, as can increasing the time of contact in medicine and affected part, the effect time limit of prolong drug, and can alleviate medicine to the friction of eyeball with overcome the problem of blurred vision.The gel for eye commodity are also arranged in the market, but mostly be thick semisolid, if directly gel drops is gone into ophthalmic, because of gel lacks good spreadability within the eye, medicine is difficult for being evenly distributed, using dosage can not accurately be controlled simultaneously, also may influence attractive in appearance and vision, needs further to improve.
Summary of the invention
The invention provides a kind of dropped in eyes and be used in body gel preparation and preparation method thereof.Dropped in eyes of the present invention be used in the body gel preparation be for a kind of in external one-tenth liquid condition, and splash into the ophthalmic preparation of ophthalmic gel attitude.The present invention is a kind of preparation that is used for the treatment of ocular infection at the body gel preparation, this gel for eye use within the eye the time of staying longer, be difficult for to run off, can keep active drug concentration, and zest is little, toxicity is low, the compatibility is good.It is an active ingredient with the anti-inflammation agent, is aided with isoosmotic adjusting agent, pH regulator agent, antiseptic, thickening agent, water etc. and makes eye-gel preparation.
Dropped in eyes of the present invention is used in the body gel preparation, is made up of following component:
Constituent content (weight %)
Anti-inflammation agent 0.1-1
Thickening agent 0.1-50
Antiseptic 0.01-0.3
Isoosmotic adjusting agent 0.1-10
It is the amount of 5-9 that the preparation pH value is regulated in the pH regulator agent
Water surplus
The anti-inflammation agent is the active component of the present invention in the body gel preparation, it be selected from following: the mixture of one or more in tobramycin, gentamycin, neomycin, chloromycetin, dexamethasone, ciprofloxacin and salt thereof, ofloxacin, levofloxacin and salt thereof, Gatifloxacin, cetylpyridinium chloride, cefmenoxime, clarithromycin, clindamycin and salt thereof, the matrine.
Thickening agent be selected from following: the mixture of one or more among poloxamer (Poloxamer), carbomer (Carbomer), polyvinyl alcohol (PVA, Polyvinyl Alcohol), hyaluronic acid sodium (HA, SodiumHyaluronat), polyvidone (PVP, Palyvidone), methylcellulose (EC, MethylCellulose), hydroxypropyl emthylcellulose (HPMC, HydroxypropylMethylcellulose), the Smart polymer gels.The poloxamer molecular weight is that 1000-16000, carbomer molecular weight are 1 * 10
6-4 * 10
6, the polyvidone molecular weight is that 5000-70000, methylcellulose molecular weight are 2 * 10
4-38 * 10
4, the hydroxypropyl emthylcellulose molecular weight is 86000.
Antiseptic be selected from following: the mixture of one or more in benzalkonium chloride, benzalkonium bromide, Metagin, second, the propyl ester.
Isoosmotic adjusting agent is to be selected from sodium chloride, glucose, mannitol, glycerol or propylene glycol.
The pH regulator agent is to adopt sodium hydroxide and/or hydrochloric acid, sulphuric acid, citric acid, sodium citrate, boric acid, sodium borate, triethanolamine.
Dropped in eyes of the present invention is used in the preparation method of body gel preparation
Step is as follows: by the weighing of above-mentioned prescription with anti-inflammation agent stirring and dissolving in water, add thickening agent again, antiseptic, isoosmotic adjusting agent stir and make dissolving.With pH regulator agent regulator solution pH value is 5-9, and solution adds water to total amount again by filtering with microporous membrane on filter, and Quality Identification is carried out in sampling, qualified after, under gnotobasis, be sub-packed in eye drip with in the bottle, packing promptly.
The physicochemical character of formulation products of the present invention:
(1) external be liquid, splashing into ophthalmic becomes gel, viscosity reduces with the increase of external carbuncle.
(2) 37 ℃ of gelling time 5-300 seconds.
Ophthalmic preparation of the present invention is applicable to ocular infections such as treatment bacterial conjunctivitis, keratitis, corneal ulcer, dacryocystisis, postoperative infection.Drip in eyelid, every day 2-3 time, each 1-2 drips, or follows the doctor's advice.
It is a kind of in external one-tenth liquid condition that dropped in eyes of the present invention is used in the body gel preparation, splashes into the ophthalmic preparation of ophthalmic gel attitude.Its toxicity is low, and zest is little, and good biocompatibility can improve patient's compliance and toleration.Compared following advantage with conventional dosage forms commonly used such as eye drop, eye ointment: 1. be liquid condition under this product room temperature, dosage is accurately control, easy to use easily, and be easy to sprawl after splashing into ophthalmic.2. gel is an aqueous matrix, and viscosity is moderate, and lubricity is good, and to the eye nonirritant, and the transparency is good, does not influence sight line, and therefore trace stain not after the use can not influence attractive in appearancely, uses comfortable.3. after gel drops was gone into ophthalmic, uniform spreading sticked to eyeball and eyelid surface and becomes gel, can not resemble most of loss the eye drop, thereby medicine is slowly discharged at eye, keep long relatively treatment time, more can bring into play therapeutical effect than eye drop, strengthen therapeutic effect.4. of the present inventionly be plasticity or pseudoplastic behavior character at the body gel preparation on rheology, viscosity reduces with nictation, and use feeling is comfortable, when not batting an eyelid, can recover viscosity again.Confirm through clinical experiment, it has significant anti-infectious function, and because the gel for eye use slow releasing function, the access times of medicine are can more similar eye drop few, so both guaranteed therapeutic effect, greatly facilitate the patient again, so dropped in eyes of the present invention is used in the body gel preparation and can be applied to clinically, have the wide development prospect.
The specific embodiment
The following examples will the present invention is further elaborated, but do not limit content of the present invention.
Embodiment 1
Get water for injection 39Kg, add tobramycin 0.25Kg, stir and make dissolving.Get poloxamer (M12000-16000) 10Kg, be sprinkled into above-mentioned solution, standing over night adds benzalkonium chloride 0.005Kg again, sodium chloride 0.4Kg, stirring and dissolving.Regulating pH with boric acid is 6, and solution adds water to total amount 50Kg by 0.22 μ m filtering with microporous membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 2
Get water for injection 39Kg, add tobramycin 0.15Kg and dexamethasone 0.05Kg, stir and make dissolving.Get poloxamer (M12000-16000) 5Kg, be sprinkled into above-mentioned solution, standing over night adds benzalkonium bromide 0.005Kg again, sodium chloride 0.4Kg, stirring and dissolving.Regulating pH with 0.1N hydrochloric acid is 5, and solution adds water to total amount 50Kg by 0.22 μ m filtering with microporous membrane on filter, and Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 3
Get water for injection 39Kg, add levofloxacin hydrochloride 0.1Kg, stir and make dissolving.Get poloxamer (M12000-16000) 5Kg and hydroxypropyl emthylcellulose (E50) 0.4Kg, be sprinkled into above-mentioned solution, standing over night adds ethyl hydroxybenzoate 0.015Kg again, glucose 0.4Kg, stirring and dissolving.Regulating pH with the 0.1N sodium hydroxide is 8, and solution filters by 0.22 μ m microporous filter membrane, adds water to total amount 50Kg on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 4
Get water for injection 45Kg, add cefmenoxime 0.5Kg, stir and make dissolving.Get carbomer (NF940) 0.15Kg and methylcellulose (A4M) 0.4Kg, be sprinkled into above-mentioned solution, standing over night adds methyl hydroxybenzoate 0.015Kg and propylparaben 0.015Kg, glycerol 0.4Kg, stirring and dissolving again.Regulating pH with the 0.1N sodium hydroxide is 7.Solution adds water to total amount 50Kg by 0.22 μ m filtering with microporous membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 5
Get water for injection 45Kg, add clindamycin 0.5Kg, stir and make dissolving.Get carbomer (NF940) 0.15Kg and hydroxypropyl emthylcellulose (E50) 0.4Kg, be sprinkled into above-mentioned solution, standing over night adds methyl hydroxybenzoate 0.015Kg and propylparaben 0.015Kg, sodium chloride 0.4Kg, stirring and dissolving again.Regulating pH with the 0.1N sodium hydroxide is 9, and solution adds water to total amount 50Kg by 0.22 μ m filtering with microporous membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Embodiment 6
Get water for injection 39Kg, add matrine 0.25Kg, stir and make dissolving.Get poloxamer (M12000-16000) 10Kg, be sprinkled into above-mentioned solution, standing over night adds benzalkonium chloride 0.005Kg again, sodium chloride 0.4Kg, stirring and dissolving.Regulating pH with boric acid is 6, and solution adds water to total amount 50Kg by 0.22 μ m filtering with microporous membrane on filter.Quality Identification is carried out in sampling, and qualified back is sub-packed in eye drip with in the bottle under gnotobasis, and packing promptly.
Claims (3)
1, a kind of dropped in eyes is used in the body gel preparation, it is characterized in that being made up of following component:
Constituent content (weight %)
Anti-inflammation agent 0.1-1
Thickening agent 10-20
Antiseptic 0.01-0.3
Isoosmotic adjusting agent 0.1-10
It is the amount of 5-9 that the preparation pH value is regulated in the pH regulator agent
Water surplus
Described thickening agent is a poloxamer, and the molecular weight of poloxamer is 12000-16000.
2, described by claim 1 at the body gel preparation, it is characterized in that
Described anti-inflammation agent be selected from following: the mixture of one or more in tobramycin, gentamycin, neomycin, chloromycetin, dexamethasone, ciprofloxacin and salt thereof, levofloxacin and salt thereof, Gatifloxacin, cetylpyridinium chloride, cefmenoxime, clarithromycin, clindamycin and salt thereof, the matrine;
Described antiseptic be selected from following: the mixture of one or more in benzalkonium chloride, benzalkonium bromide, Metagin, second, the propyl ester;
Described isoosmotic adjusting agent is to be selected from sodium chloride, glucose, mannitol, glycerol or propylene glycol;
Described pH regulator agent is to adopt sodium hydroxide and/or hydrochloric acid, sulphuric acid, citric acid, sodium citrate, boric acid, sodium borate, triethanolamine.
3, the described dropped in eyes of claim 1 is used in the preparation method of body gel preparation, it is characterized in that described preparation method step is, by the described prescription weighing of claim 1, the anti-inflammation agent is dissolved in water, adds poloxamer, antiseptic again, the isoosmotic adjusting agent stirring and dissolving, regulating pH with the pH regulator agent is 5-9, and solution adds water to total amount again by filtering with microporous membrane on filter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021365806A CN1194664C (en) | 2002-08-19 | 2002-08-19 | In-vivo gel preparatino able to be dropped in eyes and its preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021365806A CN1194664C (en) | 2002-08-19 | 2002-08-19 | In-vivo gel preparatino able to be dropped in eyes and its preparing process |
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| Publication Number | Publication Date |
|---|---|
| CN1397272A CN1397272A (en) | 2003-02-19 |
| CN1194664C true CN1194664C (en) | 2005-03-30 |
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| CNB021365806A Expired - Fee Related CN1194664C (en) | 2002-08-19 | 2002-08-19 | In-vivo gel preparatino able to be dropped in eyes and its preparing process |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100404073C (en) * | 2004-04-02 | 2008-07-23 | 北京万全阳光医药科技有限公司 | Method for preparing hard-soluble gel formulation |
| CN100464751C (en) * | 2006-04-07 | 2009-03-04 | 沈阳海普科技有限公司 | Matrine eye drip liquid, and producing method |
| CN102078284B (en) * | 2009-11-27 | 2013-06-12 | 沈阳兴齐眼药股份有限公司 | Gatifloxacin-containing gel for eyes and preparation method thereof |
| CN102949336A (en) * | 2011-08-19 | 2013-03-06 | 苏州太湖美药业有限公司 | Tobramycin ophthalmic in-situ gel eye-drops |
| CN102949331A (en) * | 2011-08-19 | 2013-03-06 | 苏州太湖美药业有限公司 | Preparation method of tobramycin ophthalmic in-situ gel eye-drops |
| CN102961390A (en) * | 2012-11-25 | 2013-03-13 | 西安泰科迈医药科技有限公司 | Ophthalmic gel medicinal composition and preparation method thereof |
| CN107224425B (en) * | 2016-03-24 | 2021-05-25 | 湖北远大天天明制药有限公司 | Preparation method of levofloxacin hydrochloride sterile gel |
| CN106265701B (en) * | 2016-08-05 | 2019-01-15 | 西南大学 | A kind of temperature sensitive hydrogel eye drops and its preparation method and application |
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2002
- 2002-08-19 CN CNB021365806A patent/CN1194664C/en not_active Expired - Fee Related
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| CN1397272A (en) | 2003-02-19 |
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Granted publication date: 20050330 Termination date: 20120819 |