CN1456350A

CN1456350A - Eye cyclosporin gel

Info

Publication number: CN1456350A
Application number: CN 02117619
Authority: CN
Inventors: 刘继东; 姚东民; 高峨; 宋长海
Original assignee: Individual
Current assignee: Individual
Priority date: 2002-05-10
Filing date: 2002-05-10
Publication date: 2003-11-19

Abstract

A cyclosporin eye gel for treating the rejection reaction of corneal transplantation, keratoconjunctival xerosis, catarrhal conjunctivitis, and chemical burn of eye is prepared from cyclosporin, boric acid, borax, trichloro-tert-butanol, etc. Its advantages are long stay time in eye and high curative effect.

Description

Eye cyclosporin gel

Affiliated technical field

---ciclosporin---makes gel for eye use first to the present invention relates to a kind of effective ingredient, be applied to the treatment of ocular disease, the following ophthalmic diseases of main treatment: 1, corneal allograft rejection, 2, corneal and conjunctival xerosis (KC), 3, vernal conjunctivitis, 4, eye chemical burn (2 degree to 4 degree).

Background technology

At present, ciclosporin ophthalmology preparation at home and abroad hospital uses in a large number, is hospital preparation, does not see launch.It is clinical that the U.S. was carrying out for three phases, domesticly declares eye drip oil preparation person.There is no the person that declares the eye cyclosporin gel both at home and abroad.

Summary of the invention

Big in order to overcome dosage, oral drugs are difficult to the deficiency by blood-eye barrier, invent a kind of gel for eye use, the ophthalmology topical, not only solved eye drop and easily diluted by tear, the problem that the ophthalmic time of staying is short, and use amount is few, improve the bioavailability of effective ingredient, increase curative effect and drug safety.

Technical scheme of the present invention is: the ciclosporin ingredient forms stable transparent mastic with card pool nurse mastic substrate, uses the back and forms the gas-pervious reticular membrane of one deck at the eye table, and effect is lasting.Its concrete feature is as follows:

The eye cyclosporin gel single preparations of ephedrine, its general eye cyclosporin gel by name; Chemistry ring by name [[(E)-(2S, 3R, 4R)-3-hydroxy-4-methyl-2-(methylamino)-6-octene acyl]-the amino butyryl of L-2-N-methyl glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl] gel for eye use; English CiclosporinOphthalmic Gel by name; The Chinese phonetic alphabet is Huanbaosu Yanyong Ningjiao; Medicine and main adjunct ingredient and the preparation of forming in following ratio that is applied to ophthalmology illness thereof: wherein containing ciclosporin is 2.0% (w/w), containing card pool nurse is 0.4% (w/w), borax is 1.0% (w/w), and boronic acid containing is 0.5% (w/w), and containing chlorobutanol is 0.3% (w/w); Be applied to the treatment of corneal allograft rejection, cornea and conjunctiva xerosis (KC), vernal conjunctivitis, eye chemical burn ophthalmology illness such as (2 degree are to 4 degree); Its preparation process is: the chlorobutanol of getting recipe quantity soaks carbomer wherein with the dissolving of 900ml water for injection, spends the night.Borax, the boric acid of getting recipe quantity add wherein, stir, and make clear gel substrate; The recipe quantity ciclosporin is ground into impalpable powder, crosses sieve No. 9, gradation is ground in the substrate under the heating condition, and moisturizing stirs to full dose; Filter with 220 mesh sieve cloth, pressure sterilizing, packing, promptly.In addition, substrate such as effective ingredient and hydroxypropyl methylcellulose series, methylcellulose series, polyvinyl alcohol series all can form gel, and card pool nurse series substrate effect is best.Among the above-mentioned preparation technology, its core technology is: (1) ciclosporin ingredient grinds to form impalpable powder (crossing sieve No. 9), (2) grinding heating (temperature range 60-80 ℃) mixed dissolution with adjunct ingredient is to guarantee the transparent key of mastic, (3) card pool nurse swelling (concentration range 0.5-5.0%) is made transparent emulsifiable paste, (4) pressure sterilizing (115 ℃, 30 minutes).

Good effect of the present invention: the development of eye cyclosporin gel and exploitation have following advantage: (1), eye cyclosporin gel directly act on the affected part, can play a role fully effectively, can reduce GI irritation and other side effect that oral drugs cause.(2), with respect to other ophthalmic preparation, gel has unrivaled advantage.Compare eye cyclosporin gel with eye drop and be difficult for being diluted by tear, within the eye the time of staying long, help main abundant absorption and utilization; Compare with the eye ointment of vaseline substrate, the eye cyclosporin gel good water solubility is cleaned easily, and pollution clothes is not easy to use.On the other hand, eye cyclosporin gel does not cause the visual field fuzzy, uses the back to form the gas-pervious reticular membrane of one deck at the eye table, all can use round the clock.This Products Development is successful, not only can fill up a blank of domestic ophthalmic remedy, also can bring good social benefit and economic benefit.(3), our enterprise is the ophthalmic remedy manufacturer of domestic specialty, is devoted to production, development, the exploitation of medicament for the eyes over more than 30 year always, actively participates in work for the public good, ophthalmic remedy accounts for more than 90% of the gross output value.

Embodiment

Prescription 1: ciclosporin 2.0g

Card pool nurse 0.4g

Borax 1.0g

Boric acid 0.5g

Chlorobutanol 0.3g

Make the 100.0g operating process:

2.. Borax, boric acid are made clear gel substrate in adding 1..

3.. ciclosporin grinds to form impalpable powder, crosses sieve No. 9, during 2. gradation grinds under the heating condition.

4. .220 mesh sieve cloth filters, pressure sterilizing, and packing, packing, promptly.

Prescription 2: ciclosporin 0.5-10.0g

Card pool nurse 0-4.0g

Borax 0-10.0g

Boric acid 0-5.0g

Chlorobutanol 0-3.0g

Make the 100.0g operating process:

1.. suitable quantity of water, the dissolving chlorobutanol adds the dissolving of card pool nurse, spends the night.

2.. Borax, boric acid are made clear gel substrate in adding 1..

4. .220 mesh sieve cloth filters, pressure sterilizing, and packing, packing, promptly.Creativeness of the present invention realizes by clinical, toxicology and pharmacology data, provides in the lump during examination as to substances.

Fig. 1 is an eye cyclosporin gel preparation technology flow chart.

Claims

1. one kind is used for the eye cyclosporin gel single preparations of ephedrine that corneal allograft rejection, cornea and conjunctiva xerosis (KC), vernal conjunctivitis, eye chemical burn (2 degree are to 4 degree) wait ophthalmology illness to treat, its general eye cyclosporin gel by name; Chemistry ring by name [[(E)-(2S, 3R, 4R)-3-hydroxy-4-methyl-2-(methylamino)-6-octene acyl]-the amino butyryl of L-2-N-methyl glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl] gel for eye use; English Ciclosporin Ophthalmic Gel by name; The Chinese phonetic alphabet is Huanbaosu Yanyong Ningjiao; Medicine and main adjunct ingredient and the preparation of forming in following ratio that is applied to ophthalmology thereof: wherein containing ciclosporin is 2.0% (w/w), containing card pool nurse is 0.4% (w/w), borax is 1.0% (w/w), and boronic acid containing is 0.5% (w/w), and containing chlorobutanol is 0.3% (w/w); Preparation process: the chlorobutanol of getting recipe quantity soaks carbomer wherein with the dissolving of 900ml water for injection, spends the night.Borax, the boric acid of getting recipe quantity add wherein, stir, and make clear gel substrate; The recipe quantity ciclosporin is ground into impalpable powder, crosses sieve No. 9, gradation is ground in the substrate under the heating condition, and moisturizing stirs to full dose; Filter with 220 mesh sieve cloth, pressure sterilizing, packing, promptly.In addition, substrate such as ciclosporin effective ingredient and hydroxypropyl methylcellulose series, methylcellulose series, polyvinyl alcohol series all can form gel, and card pool nurse series substrate effect is best.Among the above-mentioned preparation technology, its core technology is: (1) ciclosporin ingredient grinds to form impalpable powder (crossing sieve No. 9), (2) grinding heating (temperature range 60-80 ℃) mixed dissolution with adjunct ingredient is to guarantee the transparent key of mastic, (3) card pool nurse swelling (concentration range 0.5-5.0%) is made transparent emulsifiable paste, (4) pressure sterilizing (115 ℃, 30 minutes).

2. according to the described eye cyclosporin gel of claim 1, it is characterized in that this effective ingredient ciclosporin makes gel for eye first, medicine and main adjunct ingredient and the preparation of forming in following ratio that is applied to the ophthalmology illness treatment thereof: wherein ciclosporin is its active ingredient, concentration is 0.5-10.0% (w/w), it is 0-4.0% (w/w) that main adjuvant contains card pool nurse, borax is 0-10.0% (w/w), boronic acid containing is 0-5.0% (w/w), and containing chlorobutanol is 0-3.0% (w/w).