CN101342180A - Medicament composition for eyes and preparation method thereof - Google Patents
Medicament composition for eyes and preparation method thereof Download PDFInfo
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- CN101342180A CN101342180A CNA2008100489309A CN200810048930A CN101342180A CN 101342180 A CN101342180 A CN 101342180A CN A2008100489309 A CNA2008100489309 A CN A2008100489309A CN 200810048930 A CN200810048930 A CN 200810048930A CN 101342180 A CN101342180 A CN 101342180A
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Abstract
The invention relates to a medicine composition and a preparation method thereof, in particular to an ophthalmic medicine composition and a preparation method thereof. The ophthalmic medicine composition comprises an antivirus medicine with 0.005 to 5.0 weight percent of effective dose, DXM with 0.0005 to 0.1 weight percent of the effective dose and medicinal additive. The medicine composition used for curing herpes simplex keratitis can greatly enhance the recovery process of the herpes simples keratitis and deep solid herpes simples keratitis, effectively improve eye irritation symptoms, shorten healing time and reduce the recurrence rate of the herpes simples keratitis.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, a kind of medical composite for eye and preparation method thereof specifically, said composition is used for the treatment of herpes simplex keratitis.
Background technology
Herpes simplex keratitis is called for short herpes simplex virus keratitis, is the keratitis that herpes simplex virus causes, the keratopathy due to mainly being infected by herpes simplex virus I type occupies keratopathy blinding first place.According to statistics, whole world every year is infected the keratitis that causes by HSV-I nearly 1,000,000 people's blindings, and the sickness rate of China is also quite high, has every year 50000 people to lose one's sight because of the cornea viral infection or vision significantly descends.HSK has the state of an illness repeatedly, the characteristics that are difficult to cure.
The antiviral drugs such as the acyclovir (acycloguanosine of at present used treatment herpesvirus keratitis, Acyclovir, ACV), the effect of anti-HSV is more eager to excel in whatever one does than cytosine arabinoside (Cytarabine), idoxuridine (Idoxuridine), ancitabine (Ancitabine) and vidarabine (Vidarabine).But the effect that acyclovir is used is not very good, is in particular in that water solublity is relatively poor, and influence is used; In addition, acyclovir long period and repetitively administered also can produce drug resistance.
Ganciclovir (gancyclovir, Ganciclovir, DHPG) mechanism of action is similar to acyclovir, its inhibitory action to HSV is stronger 60 times than acyclovir, effect to cytomegalovirus (CMV), HSV-I and HSV-II is better than acyclovir, because of its half-life than acyclovir long (half-life is 8h), do not need repeatedly medication on the one, have advantages such as determined curative effect, toxicity is low, untoward reaction is little.In addition, the dissolubility of ganciclovir in water is bigger 3.5 times than ACV, helps the uniformity of administration, improves bioavailability.Ganciclovir in June, 1988 is first in Britain's listing, and the U.S. in 1994 and Britain ratify the treatment of keeping that the ganciclovir capsule is used for the CMV retinitis first; France approval TheaLab company ganciclovir gel for eye was treated herpetic keratitis and conjunctivitis in 1996.The domestic Eye Drops of Ganciclovir (trade name: brilliant bright) that has Wuhan Yuanda Pharmaceutical Group Co.,Ltd exclusively to go on the market in 2004 is used for the treatment of simple HSV keratitis.Ganciclovir is applied to clinical dosage form at present tablet, injection, injectable powder, capsule, eye drop, Eye ointments, intraocular implant and gel for eye use.
Penciclovir (Penciclovir, PCV) antiviral-mechanism is similar to acyclovir, and HSV-I and hepatitis B virus are had obvious activity, and it is by at first inventions such as the Michael R of Britain.Curative effect and the acyclovir of PCV are suitable, but its triphosphate is than the half-life of acyclovir triphosphate longer (PCV half-life in cell is 20 hours), and oral being difficult to absorbs, mostly be external (Snoesk R.Drugs, 1999,57:187).The listing of its raw material and preparation thereof is all arranged at present both at home and abroad, and the pharmaceutical dosage form of clinical usefulness has eye drop, gel, spray, emulsifiable paste, ointment, injection.
Because herpes simplex virus keratitis is easy to recurrence, be difficult to treatment, and usually cause serious visual disorder, and common clinically antiviral drugs, though certain curative effect is arranged as aciclovir eye drop, Eye Drops of Ganciclovir, penciclovir eye drop, but, make its effect in the practical application of viral keratitis dissatisfied because the limitation of preparation and medicine is easy to generate drug resistance.As for shallow-layer herpes simplex virus keratitis, generally use treatment such as aciclovir eye drop promptly effectively.But for epitheliated type herpes simplex keratitis and deep layer essence type herpes simplex keratitis, use the local and whole body administration of acyclovir or ganciclovir merely, the case that usually produces effect undesirable even invalid occurs, and causes the blinding ophthalmic.
Dexamethasone (Dexamethasone, dexamethasone, DEX) be a kind of well-known synthetic glucocorticoid that shows anti-inflammatory activity, have pharmacological actions such as antiinflammatory, antiendotoxin, inhibition immunity, shock and enhancing stress, it can multiple physical form carries out administration and is used for the treatment of the various inflammatory patient's condition such as autoimmune disease, allergy, inflammation, asthma and department of dermatologry, ophthalmic diseases do not have obvious adverse reaction when using the physiological dose replacement therapy.The dexamethasone eye drop is used for eye inflammation diseases such as iridocyclitis, iritis, keratitis, anaphylaxis conjunctivitis, blepharitis, dacryocystisis clinically.
Be used for the treatment of viral keratitis about hormone, it is generally acknowledged that the 17-hydroxy-11-dehydrocorticosterone eye drip forbids in epitheliated type list bleb keratitis, can impel this kind of pathological changes because of it and obviously worsen.But the concentration of this kind untoward reaction and used 17-hydroxy-11-dehydrocorticosterone has obvious relation, experimental results show that 0.1% dexamethasone solution eye drip can make experimental epitheliated type HSV keratitis worsen, and concentration is reduced to 0.003% then this untoward reaction elimination.
Trace dexamethasone comprises that for most external eyes inflammation anaphylaxis, infectivity and medicine inflammation still have good antiinflammation, and alleviates to greatest extent even eliminated various untoward reaction.The lot of documents report is suitably used micro-17-hydroxy-11-dehydrocorticosterone can promote the herpes simplex keratitis recovery from illness.This is the effect that has good inhibition immunoreactivity inflammation owing to hormone itself, and it can alleviate soaks into edema and the infringement of inflammation to organizing, and cooperates effective antiviral drugs, can shorten the course of treatment, promotes the healing of keratitis.
The deep layer herpes simplex keratitis is a kind of specific type of herpes simplex keratitis, is that direct infringement and the local immunoreation by the herpes simplex virus corneal caused.In inflammation phase, the vision height goes down, and rationally uses antiviral and glucocorticoid medicine, can make the most of absorption of corneal edema, and the vision of remaining valid.The Secondary cases herpes simplex keratitis is its recurrent to the bigger main cause of inpairment of vision, causes course of disease delay, develops into the infringement of deep layer essence type easily.Deep layer herpes simplex keratitis patient has the medical history of recurrence mostly, corneal epithelium is generally normal, and corneal edema thickens obviously, and tunica uvea reaction is in various degree often arranged, treatment should be under effective antiviral treatment, careful glucocorticoid with low concentration, low dose.At present also there is the diagnosis and treatment doctor that ganciclovir is united the report that trace dexamethasone is treated herpesvirus keratitis clinically.
But because need distinguish administration during two kinds of eye drop drug administrations and need repeatedly eye dripping (as the ganciclovir eye drip, every day 6 times, each 1; The acyclovir eye drip needs each 12 hours 1 time; The dexamethasone eye drip, every day 3 times), use like this and inconvenience, when medication, bring very big puzzlement for patient and medical personnel, make that medication patient's use compliance is poor.
In order to improve the clinical application demand, improve patient's compliance, therefore, we are mixed with into drug combination preparation with the antiviral drugs ganciclovir of effective dose with glucocorticoid medicine dexamethasone low dose of, low concentration, and the antiviral drugs penciclovir of effective dose and the glucocorticoid medicine dexamethasone of low dose, low concentration are mixed with into drug combination preparation.
By patent searching and document, do not have ganciclovir and dexamethasone, penciclovir and dexamethasone patent and the document that is prepared into the ophthalmic drug combination preparation that combine openly reported.
Summary of the invention
Purpose of the present invention is exactly the defective at existing treatment herpesvirus keratitis medicine, a kind of medical composite for eye and its production and use is provided, this pharmaceutical composition is used for the treatment of herpes simplex keratitis, particularly to epitheliated type herpes simplex keratitis and deep layer essence type herpes simplex keratitis good effect.
Technical scheme of the present invention is achieved in that it comprises the antiviral drugs that effective dose is 0.005-5.0wt%, dexamethasone and the medicinal auxiliary agent that effective dose is 0.0005-0.1wt%.
Wherein said antiviral drugs is ganciclovir, penciclovir or they are at pharmaceutically acceptable salt.Described dexamethasone is its pharmaceutically acceptable salt.
The present invention's technical scheme preferably is: described compositions comprises the ganciclovir that effective dose is 0.1-3.0wt%, dexamethasone and the medicinal auxiliary agent that effective dose is 0.001-0.003wt%.
The present invention another preferably technical scheme be: described compositions comprises the penciclovir that effective dose is 0.1-3.0wt%, dexamethasone and the medicinal auxiliary agent that effective dose is 0.001-0.003wt%.
The pharmaceutical preparation of pharmaceutical composition of the present invention is eye drop, eye ointment or gel for eye use.
We are surprised to find under study for action, the pharmaceutical composition of ganciclovir/dexamethasone and the pharmaceutical composition of penciclovir/dexamethasone have particularly produced significant synergistic therapeutic action aspect epitheliated type herpes simplex keratitis and the deep layer essence type herpes simplex keratitis at the treatment herpes simplex keratitis, obviously alleviated the lesion degree of HSV, quicken the keratopathy healing, alleviated symptom.Pharmaceutical composition of the present invention had both been given full play to the good antiinflammation of hormone controlling inflammation, alleviate and soak into edema and the unfavorable factors such as infringement of inflammation organizing, improved the curative effect of the anti-HSV of ganciclovir again, reduced the drug resistance of medicine, prevent the knock-on and the recurrence of herpes simplex virus keratitis, improved the safety of administration, thereby shorten the course of treatment, promote the healing of keratitis, reach the dual function of the treatment and the shortening course of disease.Therefore, pharmaceutical composition of the present invention is used for the particularly treatment of epitheliated type herpes simplex keratitis and deep layer essence type herpes simplex keratitis of herpes simplex keratitis.
Two kinds of medicine performance synergistic therapeutic actions in the drug combination preparation improve clinical efficacy, and this also is that we design one of original intention of this drug combination preparation.In addition, pharmaceutical composition of the present invention is easy to use simple and direct, has avoided having improved patient's use compliance, thereby having improved the safety of administration because different pharmaceutical is contained in a puzzlement of bringing to patient and medical personnel when taking medicine scheme.
Consider that from the science and the reasonability of pharmaceutical compositions preparation we test by drug compatibility, have proved that ganciclovir and dexamethasone have the good compatibility on physical property and chemical.
In like manner, we test by drug compatibility, have proved that penciclovir and dexamethasone have the good compatibility on physical property and chemical.
In an embodiment of the present invention, the pharmaceutical composition of eye usefulness comprises eye drop, eye ointment, gel for eye use.
According to clinical usual amounts, the present invention prepares ganciclovir/dexamethasone compositions eye drop (8ml/ bottle), between its two kinds of main compositions chemical reaction does not take place, and outward appearance, pH value, content do not have obvious change.After measured, PH is between 5.2-8.0.Show that through the eye dripping test no eye irritation does not find that the corneal epithelium toxic reaction takes place.
The PH of above-mentioned eye drop is 5.2-8.0, preferred PH6.0-7.5, and ganciclovir content is 0.01-0.5wt%, preferred 0.05-0.25wt%; Dexamethasone content is 0.0005-0.1wt%, preferred 0.001-0.003wt%.Described auxiliary agent is water for injection, cosolvent, osmotic pressure regulator, PH regulator, antiseptic etc.Wherein the PH regulator is phosphate buffer, borate buffer solution, preferred boric acid-sodium borate; Cosolvent is tween 20, Tween-40, tween 80, preferred tween 80, and its content is 0.05-0.35wt%; Antiseptic is one or more mixture in benzalkonium bromide, Benzalkonii Chloridum, the parabens, preferred benzalkonium bromide, and its content is 0.008-0.012wt%; Osmotic pressure regulator is sodium chloride and/or mannitol, and its content is 0.25-0.30wt%.
According to clinical usual amounts, chemical reaction does not take place between its two kinds of main compositions in the penciclovir that the present invention prepares/dexamethasone compositions eye drop (8ml/ bottle), and outward appearance, pH value, content do not have obvious change.After measured, PH is between 5.2-8.0.Show that through the eye dripping test no eye irritation does not find that the corneal epithelium toxic reaction takes place.
The PH of above-mentioned eye drop is 5.2-8.0, preferred PH6.0-7.5, and penciclovir content is 0.01-0.5wt%, preferred 0.05-0.25wt%; Dexamethasone content is 0.0005-0.1wt%, preferred 0.001-0.003wt%.Described auxiliary agent is water for injection, cosolvent, osmotic pressure regulator, PH regulator, antiseptic etc.Wherein the PH regulator is phosphate buffer, borate buffer solution, preferred boric acid-sodium borate; Cosolvent is tween 20, Tween-40, tween 80, preferred tween 80, and its content is 0.05-0.35wt%; Antiseptic is one or more mixture in benzalkonium bromide, Benzalkonii Chloridum, the parabens, preferred benzalkonium bromide, and its content is 0.008-0.012wt%; Osmotic pressure regulator is sodium chloride and/or mannitol, and its content is 0.25-0.30wt%.
According to clinical usual amounts, the present invention prepares ganciclovir/dexamethasone compositions Eye ointments (2g/ props up), between its two kinds of main compositions chemical reaction does not take place, and outward appearance, pH value, content do not have obvious change.After measured, PH is between 5.2-8.4.Show that through the eye dripping test no eye irritation does not find that the corneal epithelium toxic reaction takes place.
Above-mentioned Eye ointments, ganciclovir content are 0.1-3.0wt%, preferred 0.5-2.0wt%; Dexamethasone content is 0.0005-0.1wt%, preferred 0.001-0.003wt%.Described auxiliary agent comprises 80-85wt% Yellow Vaselin, 10-15wt% lanoline, 5-10wt% liquid paraffin etc.
According to clinical usual amounts, the present invention prepares penciclovir/dexamethasone compositions Eye ointments (2g/ props up), between its two kinds of main compositions chemical reaction does not take place, and outward appearance, pH value, content do not have obvious change.After measured, PH is between 5.2-8.4.Show that through the eye dripping test no eye irritation does not find that the corneal epithelium toxic reaction takes place.
Above-mentioned Eye ointments, penciclovir content are 0.1-3.0wt%, preferred 0.5-2.0wt%; Dexamethasone content is 0.0005-0.1wt%, preferred 0.001-0.003wt%.Described auxiliary agent comprises 80-85wt% Yellow Vaselin, 10-15wt% lanoline, 5-10wt% liquid paraffin etc.
According to clinical usual amounts, the present invention prepares ganciclovir/dexamethasone compositions gel for eye use (5g/ props up), between its two kinds of main compositions chemical reaction does not take place, and outward appearance, pH value, content do not have obvious change.After measured, PH is between 5.3-8.6.Show that through the eye dripping test no eye irritation does not find that the corneal epithelium toxic reaction takes place.
Above-mentioned gel for eye use, ganciclovir content are 0.01-0.5wt%, preferred 0.05-0.20wt%; Dexamethasone content is 0.001-0.01wt%, preferred 0.001-0.003wt%.Described ophthalmic gel base is one or more a mixture of carbomer, hydroxypropyl cellulose, xanthan gum, preferred carbomer.The concentration of used ophthalmic gel base is 0.1-15.0wt%.Described assistant packet explanatory note in brackets is penetrated water, cosolvent, osmotic pressure regulator, PH regulator, antiseptic etc.Wherein cosolvent is tween 20, Tween-40, tween 80, preferred tween 80, and its content is 0.05-0.35wt%; The PH regulator is one or more mixed solutions in sodium hydrate aqueous solution, triethanolamine solution, ammonia, sodium carbonate liquor, the alkaline buffer, preferred triethanolamine, and its content is 0.1-10.0wt%; Antiseptic is one or more mixture in benzalkonium bromide, Benzalkonii Chloridum, benzoic acid and sodium benzoate, the parabens, preferred benzalkonium bromide, and its content is 0.01-0.1wt%; Osmotic pressure regulator is sodium chloride and/or mannitol, and its content is 0.1-10.0wt%.
According to clinical usual amounts, the present invention prepares penciclovir/dexamethasone pharmaceutical composition gel for eye use (5g/ props up), between its two kinds of main compositions chemical reaction does not take place, and outward appearance, pH value, content do not have obvious change.After measured, PH is between 5.3-8.6.Show that through the eye dripping test no eye irritation does not find that the corneal epithelium toxic reaction takes place.
Above-mentioned gel for eye use, penciclovir content are 0.01-0.5wt%, preferred 0.05-0.20wt%; Dexamethasone content is 0.001-0.01wt%, preferred 0.001-0.003wt%.Described ophthalmic gel base is one or more a mixture of carbomer, hydroxypropyl cellulose, xanthan gum, preferred carbomer.The concentration of used ophthalmic gel base is 0.1-15.0wt%.Described assistant packet explanatory note in brackets is penetrated water, cosolvent, osmotic pressure regulator, PH regulator, antiseptic etc.Wherein cosolvent is tween 20, Tween-40, tween 80, preferred tween 80, and its content is 0.05-0.35wt%; The PH regulator is one or more mixed solutions in sodium hydrate aqueous solution, triethanolamine solution, ammonia, sodium carbonate liquor, the alkaline buffer, preferred triethanolamine, and its content is 0.1-10.0wt%; Antiseptic is one or more mixture in benzalkonium bromide, Benzalkonii Chloridum, benzoic acid and sodium benzoate, the parabens, preferred benzalkonium bromide, and its content is 0.01-0.1wt%; Osmotic pressure regulator is sodium chloride and/or mannitol, and its content is 0.1-10.0wt%.
Therefore the present invention has particularly produced significant synergistic therapeutic action aspect epitheliated type herpes simplex keratitis and the deep layer essence type herpes simplex keratitis at the treatment herpes simplex keratitis, obviously alleviated the lesion degree of HSV, quickened the keratopathy healing, alleviate symptom, reached the dual function of the treatment and the shortening course of disease.And easy to use simple and direct in clinical, avoided having improved patient's use compliance, thereby having improved the safety of administration because different pharmaceutical is contained in a puzzlement of bringing to patient and medical personnel when taking medicine scheme.
The specific embodiment
Below we further specify the present invention by following examples, rather than be used for it is limited.
Embodiment 1: the preparation of ganciclovir/dexamethasone compositions eye drop:
1) prescription:
Ganciclovir 8g
Dexamethasone 0.08g
Boric acid 1g
Sodium borate 1.5g
Hyaluronate sodium 8g
Tween 80 12g
Bromo geramine 0.8g
Sodium chloride 20g
Water for injection is to 8000ml
Make 1000 of eye drops altogether
2) preparation method:
By aseptic manipulation, get ganciclovir, dexamethasone and tween 80 and place retort, add the injection water, heating makes it dissolving, adds other auxiliary agents in the above-mentioned prescription, and transferring pH with hydrochloric acid is 6.0-7.0, boil 5-10min, be cooled to room temperature, under cleaning condition,, add adding to the full amount of water for injection with 0.22 μ m filtering with microporous membrane, stir evenly, sampling and measuring PH and content, qualified back sterile filling seals promptly in the 8mL eye-drop liquid bottle.
3) stability test (Chinese Pharmacopoeia. two [S] 2005: appendix 178.)
Sample is carried out stability test under temperature (40 ± 2) ℃, relative humidity (75 ± 5) % condition, at duration of test the 1st, 2,3,4,5, each sampling in 6 months is once investigated indexs such as its appearance luster, PH, content, and every index is all in the quality standard prescribed limit during 6 months as a result.
4) irritation test
Select 4 of healthy adult rabbit, body constitution amount 2.5-3.0kg, every rabbit left eye splashes into composite eye drop 0.1mL of the present invention, right eye splashes into normal saline 0.1mL, by relevant criterion observe scoring (Zhang Yuanpei. pharmacological experiment [M]. the 2nd edition. Beijing: People's Health Publisher, 1996:223), the result does not have the eye irritation, does not find that the corneal epithelium toxic reaction takes place.Show this product nonirritant, eye safety.
5) microbial limit and sterility test (Chinese Pharmacopoeia. two [s] .2005: appendix 93,89.)
Detect by the Chinese Pharmacopoeia requirement, measurement result meets the requirements.
The result shows that drug combination preparation of the present invention has good stability, to tame lagophthalmos nonirritant.This preparation technology is simple, and quality control method is reliable, can satisfy clinical ophthalmology medication needs.
Embodiment 2: the preparation of penciclovir/dexamethasone compositions eye drop:
1) prescription:
Penciclovir 8g
Dexamethasone 0.16g
Boric acid 1g
Sodium borate 1.5g
Tween 80 12g
Bromo geramine 0.8g
Sodium chloride 24g
Water for injection is to 8000ml
Make 1000 of eye drops altogether
2) preparation method: with embodiment 1.
Embodiment 3: the preparation of ganciclovir/dexamethasone compositions eye drop:
Preparation method: in the Eye Drops of Ganciclovir of commercially available 8ml (8mg), add dexamethasone injection (specification 1ml: 1mg) 0.16ml (0.16mg), sampling and measuring PH and content, qualified after, at the cleaning condition lower seal, room temperature preserves, standby.
Embodiment 4: the preparation of ganciclovir/dexamethasone compositions eye ointment:
1) prescription:
Ganciclovir 20g
Dexamethasone 0.24g
Yellow Vaselin 1600g
Lanoline 240g
Liquid paraffin is in right amount to 2000g
Make 1000 of eye ointment altogether
2) preparation method:
Ganciclovir and dexamethasone are ground, are screened to below the 75 μ m; With the auxiliary agent heating and melting, after the filtration, be heated to 130-135 ℃ of sterilization 60-80min in addition, be cooled to room temperature; The ganciclovir and the dexamethasone micropowder that ground is moistening with sterilized liquid paraffin, add the sterilization auxiliary agent and stir evenly, sampling and measuring PH and content, qualified back sterile filling.
Embodiment 5: the preparation of penciclovir/dexamethasone compositions eye ointment:
1) prescription:
Penciclovir 20g
Dexamethasone 0.16g
Yellow Vaselin 1600g
Lanoline 200g
Liquid paraffin is in right amount to 2000g
Make 1000 of eye ointment altogether
2) preparation method: with embodiment 4.
Embodiment 6: the preparation of ganciclovir/dexamethasone compositions gel for eye use:
1) prescription:
Ganciclovir 7.5g
Dexamethasone 0.15g
Carbomer 25g
Tween 80 10g
Mannitol 75g
10% sodium hydroxide solution 50-100g
Benzalkonium bromide 0.375g
Water for injection adds to 5000g
Make 1000 of gel for eye use altogether
2) preparation method:
With the recipe quantity carbomer, add the quality distilled water, swelling; In addition recipe quantity principal agent ganciclovir, dexamethasone and mannitol, benzalkonium bromide etc. are dissolved in the distilled water, stirring makes its dissolving, after 0.30 μ m microporous filter membrane degerming filters, filtrate is added in the carbomer gel substrate, regulate PH7.0-8.5 with 10% sodium hydroxide solution, add water to capacity, stir and make into even gel, 115 ℃ of sterilization 30min, sampling and measuring PH and content, after qualified, aseptic subpackaged, promptly.
Embodiment 7: the preparation of penciclovir/dexamethasone compositions gel for eye use:
1) prescription:
Penciclovir 10g
Dexamethasone 0.15g
Hydroxypropyl cellulose 50g
Sodium chloride 50g
Triethanolamine solution 150-500g
Nipalgin 1g
Water for injection adds to 5000g
Make 1000 of gel for eye use altogether
2) preparation method:
The recipe quantity hydroxypropyl cellulose is added quality distilled water, swelling; In addition recipe quantity principal agent ganciclovir, dexamethasone and sodium chloride, nipalgin etc. are dissolved in the distilled water, stirring makes its dissolving, after 0.30 μ m microporous filter membrane degerming filters, filtrate is added in the hydroxypropyl cellulose gel substrate, regulate PH7.0-8.5 with triethanolamine, adding distil water stirs and makes into even gel to capacity, 115 ℃ of sterilization 30min, sampling and measuring PH and content, after qualified, aseptic subpackaged, promptly.
The ganciclovir that the present invention makes/dexamethasone pharmaceutical composition gel for eye outward appearance is sparkling and crystal-clear, uses carbomer as substrate, can alleviate the toxicity of antiviral drugs to eye table epithelium, effectively protects cornea, conjunctival epithelial cell.Dosing eyes has good biocompatibility, and zest is little, in the effect time limit that simultaneously can prolong drug, reduces administration number of times, avoids drug wastage, improves advantages such as bioavailability.
Embodiment 8: the ganciclovir of above-mentioned preparation/dexamethasone compositions gel for eye use carries out following effect experiment and safety evaluatio:
1. effect experiment
Use the HSV-I infected rabbits, set up the herpes simplex keratitis model, observe the therapeutical effect of ganciclovir/dexamethasone compositions gel for eye use, establish simultaneously that 0.15% ganciclovir gel for eye use is made positive control and blank substrate is made negative control the rabbit herpes simplex keratitis.Result of the test sees Table 1:
Table 1 ganciclovir/dexamethasone compositions gel for eye use is to rabbit herpes simplex keratitis observation of curative effect
Remarks: ganciclovir/dexamethasone compositions gel for eye use and 0.15% ganciclovir gel for eye use compare, ▲ P＜0.05; ▲ ▲ P＜0.01
Ganciclovir/dexamethasone compositions gel for eye use and blank substrate are compared, ◆ P＜0.05; ◆ ◆ P＜0.01
Ganciclovir/dexamethasone compositions gel for eye amount test of significance of coefficient of correlation, ● P＜0.05; ● ● P＜0.01
Conclusion: ganciclovir/dexamethasone compositions gel for eye can alleviate the lesion degree of HSV, quickens the keratopathy healing, relief of symptoms.Each concentration ganciclovir/dexamethasone compositions gel for eye use promptly demonstrates curative effect in treatment after 3 days, and has an a certain amount of effect relationship, compare with 0.15% ganciclovir gel for eye use, curative effect occurs early, as the 3rd day curative effect integration, 0.15%, 0.20% ganciclovir/dexamethasone compositions gel for eye use by comparison, obviously increase, and this moment ganciclovir gel for eye use and negative control ratio, still no significant difference.And at the 7th day, 0.15%, 0.20% ganciclovir/dexamethasone compositions gel for eye group, the keratopathy aspect all is starkly lower than ganciclovir gel for eye use group.
In sum, ganciclovir/dexamethasone compositions gel for eye use curative effect is better than similar antiviral ophthalmic preparation.
2. local application's toxicity test
1) single-dose irritation test
After single gave ganciclovir/dexamethasone compositions gel for eye use, it is no abnormal that rabbit cornea does not have ulcer, muddiness, iris, and light reflex exists, and conjunctiva does not have edema, do not find that the corneal epithelium toxic reaction takes place.Its zest scoring sees Table 2:
Lagophthalmos irritant reaction score value behind table 2 single-dose
2) multiple dosing irritation test
Repeatedly give with ganciclovir/dexamethasone compositions gel for eye use after, rabbit cornea does not see that cornea, iris etc. are unusual, conjunctiva does not have edema, does not find that the corneal epithelium toxic reaction takes place.Its zest scoring sees Table 3:
Lagophthalmos irritant reaction score value behind table 3 multiple dosing
Conclusion: ganciclovir/dexamethasone compositions gel for eye use single and repeatedly eye should administration after, to the equal nonirritant of eye.
Claims (6)
1, a kind of medical composite for eye, it comprises the antiviral drugs that effective dose is 0.005-5.0wt%, dexamethasone and the medicinal auxiliary agent that effective dose is 0.0005-0.1wt%.
2, a kind of medical composite for eye according to claim 1, wherein said antiviral drugs are ganciclovir, penciclovir or they are at pharmaceutically acceptable salt.
3, a kind of medical composite for eye according to claim 1, wherein said dexamethasone is its pharmaceutically acceptable salt.
4, according to claim 1,2 or 3 described a kind of medical composite for eye, wherein said compositions comprises the ganciclovir that effective dose is 0.1-3.0wt%, dexamethasone and the medicinal auxiliary agent that effective dose is 0.001-0.003wt%.
5, according to claim 1,2 or 3 described a kind of medical composite for eye, wherein said compositions comprises the penciclovir that effective dose is 0.1-3.0wt%, dexamethasone and the medicinal auxiliary agent that effective dose is 0.001-0.003wt%.
6, a kind of medical composite for eye according to claim 5, wherein the pharmaceutical preparation of this pharmaceutical composition is eye drop, eye ointment or gel for eye use.
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| CN105902484A (en) * | 2016-05-16 | 2016-08-31 | 湖北丽益医药科技有限公司 | Ganciclovir ophthalmic gel and preparation method thereof |
| CN109316445A (en) * | 2018-11-15 | 2019-02-12 | 塔里木大学 | It is a kind of for ox, the spray of sheep eye disease |
| WO2021063408A1 (en) * | 2019-09-30 | 2021-04-08 | 神农医药科技有限公司 | Preparation of drug for treating alzheimer's disease |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902484A (en) * | 2016-05-16 | 2016-08-31 | 湖北丽益医药科技有限公司 | Ganciclovir ophthalmic gel and preparation method thereof |
| CN109316445A (en) * | 2018-11-15 | 2019-02-12 | 塔里木大学 | It is a kind of for ox, the spray of sheep eye disease |
| WO2021063408A1 (en) * | 2019-09-30 | 2021-04-08 | 神农医药科技有限公司 | Preparation of drug for treating alzheimer's disease |
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