CN110200956A - A kind of ophthalmic external use medicine compositions - Google Patents
A kind of ophthalmic external use medicine compositions Download PDFInfo
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- CN110200956A CN110200956A CN201910644421.0A CN201910644421A CN110200956A CN 110200956 A CN110200956 A CN 110200956A CN 201910644421 A CN201910644421 A CN 201910644421A CN 110200956 A CN110200956 A CN 110200956A
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7032—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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Abstract
The present invention provides a kind of ophthalmic external use medicine compositions, belong to medicinal preparation field.The ophthalmic external use medicine compositions include effective component and auxiliary material, and the effective component includes carnosic acid；The mass percent that the carnosic acid accounts for described pharmaceutical composition is 0.1~0.5%.Ophthalmic external use medicine compositions provided by the invention can treat retinal light damage, protect retina.
Description
Technical field
The present invention relates to medicinal preparation technical fields, and in particular to a kind of ophthalmic external use medicine compositions.
Background technique
Retinal light damage is the common multiple factor of one kind of blinding, is such as not treated in time, can cause the view of irreversibility
Power is lost.Domestic and international many ophthalmologists carried out numerous studies to this pathological process, including clinical diagnosis and treatment and experimentally ground
Study carefully, at present still without a comparatively ideal therapeutic scheme.The especially traumatic administration of intraocular injection, injection, which is repeated several times, to increase
Add the incidence of infectious endophthalmitis.
Carnosic acid (carnosic acid) is one of herbal medicine rosemary component, and molecular formula is C20H28O4, molecular weight
It is 3650-09-7 for 332.4339, CAS registration number, yellow powder has antioxidation, is usually used in food additives or agriculture
With.Gangliosides (GMI) are a kind of glycosphingo-lipids containing sialic acid, are present in mammalian cell, especially neural
Content highest in the after birth of first cell is that the natural component part GMI of neuron membrane rises in nerve to occur, growth and differentiation
To essential effect.
Summary of the invention
In view of technical problem present in background technique, the purpose of the present invention is to provide a kind of topical therapeutic effects
The ophthalmic external use medicine compositions for the treatment of retinal light damage, protection retinal health good, property is stable, toxic side effect is small.
In order to achieve the above-mentioned object of the invention, the present invention the following technical schemes are provided:
The present invention provides a kind of ophthalmic external use medicine compositions, including effective component and auxiliary material, the effective component packet
Include carnosic acid；The mass percent that the carnosic acid accounts for described pharmaceutical composition is 0.1~0.5%.
Preferably, the effective component further includes ganglioside；The matter of the ganglioside and the carnosic acid
Amount is than being 1~3:1.
Preferably, the dosage form of described pharmaceutical composition includes eye drops, gel for eye use or spongarion.
Preferably, when the dosage form of described pharmaceutical composition is eye drops or gel for eye use, described pharmaceutical composition is also wrapped
Include bacteriostatic agent；The bacteriostatic agent is thimerosal, quaternary ammonium salt bacteriostatic agent, Domiphen, Xian Bitai, anesin, parabens
Bacteriostatic agent and three pears acid in any one or more；The mass ratio of the bacteriostatic agent and the carnosic acid be (0.002~
0.5): (0.1~1.0).
Preferably, when the dosage form of institute's pharmaceutical composition is eye drops or gel for eye use, finished product is adjusted using pH adjusting agent
The pH value of medicament is 5.5~7.0；The pH adjusting agent is sodium hydroxide, in hydrochloric acid, sodium citrate, the minor official acid of Chinese holly, boric acid, borax
Any one or more.
Preferably, when the dosage form of institute's pharmaceutical composition is eye drops, the auxiliary material includes thickener；The thickener is
Any one of hydroxypropyl methylcellulose, methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone, polycarbophil
Or it is a variety of；The mass ratio of the thickener and the carnosic acid is (0.1~1.0): (0.1~1.0).
Preferably, when the dosage form of institute's pharmaceutical composition is gel for eye use, the auxiliary material includes thickener；The thickener
For hydroxypropyl methylcellulose, methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl cellulose, card wave
Any one or more of nurse, chondroitin sulfate, polycarbophil；The mass ratio of the thickener and the carnosic acid is
(0.5~5.0): (0.1~1.0).
Preferably, when the dosage form of institute's pharmaceutical composition is eye drops, eye drops is adjusted using sodium chloride and/or mannitol
The osmotic pressure molar density of finished product medicament is 250~350mOsmol/kg.
Preferably, when the dosage form of institute's pharmaceutical composition is spongarion, in the described pharmaceutical composition of every 100 mass parts also
Including 8~15 mass parts of wool grease, 2~10 mass parts of liquid paraffin, 75~90 mass parts of yellow petroleum jelly.
The utility model has the advantages that the present invention provides a kind of ophthalmic external use medicine compositions, including effective component and auxiliary material, it is described to have
Imitating ingredient includes carnosic acid；The mass percent that the carnosic acid accounts for described pharmaceutical composition is 0.1~0.5%.This hair
The bright ophthalmic external use medicine compositions have treatment retinal light damage, protection view using carnosic acid as main pharmacodynamics raw material
The effect of nethike embrane health.
The present invention preferably adds ganglioside liquid on the basis of carnosic acid and assists as drug effect, and is equipped with common system
Eye medicinal preparation made of agent auxiliary material.Ganglioside is used to prepare carnosic acid eye-drops preparations, helps to enhance rat-tail
The effect of oxalic acid treats retinal damage, protects retinal health.
In the present invention, carnosic acid, ganglioside dosage by its weight ratio be preferably carnosic acid: ganglioside
=1:1~3 can be prepared into eye drops, gel for eye use, Eye ointments etc., and the content of carnosic acid is in every 100 parts by weight medicament
0.1~0.5 parts by weight.In addition, the dosage form of pharmaceutical composition of the present invention is also other than eye drops, gel for eye use, spongarion
It can be the dosage form that any one described in pharmacy is suitable for eye local topical.
Detailed description of the invention
Fig. 1 is om observation result described in the embodiment of the present invention 12.
Specific embodiment
The present invention provides a kind of ophthalmic external use medicine compositions, including effective component and auxiliary material.In the present invention, described
Effective component includes carnosic acid；The carnosic acid is main pharmacodynamics raw material；The carnosic acid accounts for described pharmaceutical composition
Mass percent be 0.1~0.5%, preferably 0.2~0.4%, more preferably 0.25~0.35%.
In the present invention, it is also preferable to include gangliosides for the effective component；The ganglioside and the rat-tail
The mass ratio of oxalic acid is preferably 1~3:1, more preferably 1.2~2:1.The addition of the ganglioside helps to enhance rat-tail
The effect of oxalic acid treats retinal damage, protects retinal health.
The present invention is not particularly limited the source of the carnosic acid and the ganglioside, this field conventional commercial
The product for meeting medicinal standard.
Preferably using carnosic acid as pharmacodynamic raw materials, addition ganglioside assists the present invention as drug effect, and is equipped with common
Pharmaceutical adjunct it is prepared at eye medicinal preparation.In the present invention, the dosage form of described pharmaceutical composition preferably include eye drops,
Gel for eye use or spongarion.
In the present invention, when the dosage form of described pharmaceutical composition is eye drops or gel for eye use, described pharmaceutical composition
It is also preferable to include bacteriostatic agents.So-called any bacteriostatic agent, preferably thimerosal, quaternary ammonium in pharmacy can be used in the bacteriostatic agent
Salt bacteriostatic agent, Domiphen, Xian Bitai, anesin, parabens bacteriostatic agent and three pears acid in any one or more.
The dosage of the bacteriostatic agent is determined by routine dose in pharmacy；Such as, 1. 0.002%~0.005% thimerosal；2. quaternary ammonium salt
(including benzalkonium chloride, benzalkonium bromide), Domiphen, Xian Bitai etc., effective concentration are 0.002%~0.01%；3. alcohols is commonly used
0.3~0.6% anesin；4. parabens commonly use 0.03~0.06% ethyl hydroxy benzoate；5. acids, such as 0.01~
0.08% 3 pears acid.Above each material concentration is volume-weight percent, i.e., every hundred milliliters contain grams.In the present invention,
The mass ratio of the bacteriostatic agent and the carnosic acid is preferably (0.002~0.5): (0.1~1.0), more preferably (0.01~
0.1): (0.1~0.5).
In the present invention, when the dosage form of institute's pharmaceutical composition is eye drops or gel for eye use, present invention preferably uses pH
The pH value that regulator adjusts finished product medicament is 5.5~7.0, more preferably 6~6.5.PH adjusting agent of the present invention is preferably hydrogen
The minor official acid of sodium oxide molybdena, hydrochloric acid, sodium citrate, Chinese holly, boric acid, any one or more in borax.
In the present invention, when the dosage form of institute's pharmaceutical composition is eye drops, auxiliary material of the present invention preferably includes to thicken
Agent.The thickener be preferably hydroxypropyl methylcellulose, methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone,
Any one or more of polycarbophil, can be used different polymerization degree, and eye drops is finally made to reach suitable viscosity.In the present invention
In, the mass ratio of the thickener and the carnosic acid is preferably (0.1~1.0): (0.1~1.0), more preferably (0.1~
0.3): (0.1~0.5).
In the present invention, when the dosage form of institute's pharmaceutical composition is gel for eye use, the auxiliary material includes thickener；The increasing
Thick dose for hydroxypropyl methylcellulose, methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl cellulose,
Any one or more of carbomer, chondroitin sulfate, polycarbophil；The mass ratio of the thickener and the carnosic acid
Preferably (0.5~5.0): (0.1~1.0), more preferably (2~4): (0.1~0.5).
In the present invention, when the dosage form of institute's pharmaceutical composition is eye drops, it is preferable to use sodium chloride and/or mannitol tune
The osmotic pressure molar density for saving eye drops finished product medicament is preferably 250~350mOsmol/kg, more preferably 280~
320mOsmol/kg。
In the present invention, when the dosage form of institute's pharmaceutical composition is spongarion, the described pharmaceutical composition of every 100 mass parts
In it is also preferable to include 8~15 mass parts of wool grease, 2~10 mass parts of liquid paraffin, 75~90 mass parts of yellow petroleum jelly；Institute
The mass parts for stating wool grease are more preferably 10~12；The mass parts of the liquid paraffin are more preferably 4~8, more preferably 5
~6；The mass parts of the yellow petroleum jelly are more preferably 80~85.
The present invention is not particularly limited the source of above-mentioned each auxiliary material, this field conventional commercial product.The present invention couple
The preparation method of above-mentioned each dosage form is not particularly limited, the difference that this field is required according to dosage form, using different auxiliary material or technique
The dosage form of needs is prepared.
Technical solution provided by the invention is described in detail below with reference to embodiment, but they cannot be understood
For limiting the scope of the present invention.
Examples 1 to 3
1 Examples 1 to 3 of table prepares the raw material components and dosage of carnosic acid eye drops
Preparation method: dissolving carnosic acid full dose with appropriate water for injection, and ganglioside stirring and dissolving is added, and will separately increase
Thick dose lets cool its dispersion with water for injection, separately dissolves pH adjusting agent, osmotic pressure regulator, bacteriostatic agent with water for injection, stirs evenly
Filtering merges two liquid, adds the mixed liquor of the carnosic acid, ganglioside that have dissolved, add to the full amount of water for injection, mistake
Filter, packing to get.It the use of the pH value that pH adjusting agent adjusts finished product eye drops is 5.5~7.0.
Embodiment 4~6
2 embodiment 4~6 of table prepares the raw material components and dosage of carnosic acid gel for eye use
Preparation method: first with water for injection dissolution thickener let cool its dispersion, separately with water for injection dissolve pH adjusting agent,
Bacteriostatic agent dissolves carnosic acid and ganglioside with this solution, then plus the thickener that has dissolved, mend and inject water to institute
Need volume, it is aseptic subpackaged to get.
Embodiment 7~9
3 embodiment 7~9 of table prepares the raw material components and dosage of carnosic acid spongarion
Preparation method: Eye ointments is made using the production method of Eye ointments common in pharmacy, takes carnosic acid, nerve
The mixing of glycosides ester is saved, appropriate sterilized, cooling liquid paraffin is added, is ground into thin paste, crosses 200 meshes, then be gradually added into nothing
Bacterium, the lanolin of filtration, yellow petroleum jelly mixture, mix to get.The utensil and packing container used of preparing must sterilize.
Experimental example 10
The stability test of carnosic acid eye drops
(1) accelerated test: using the 0.3% carnosic acid eye drops by the preparation of 2 method of the embodiment of the present invention in commercially available packet
Under the conditions of dress, it is put into climatic chamber, is placed under conditions of 40 DEG C ± 2 DEG C of temperature, relative humidity 25% ± 5%, respectively at
It samples within 1st, 2,3,6 month, is measured according to quality standard draft on time.It the results are shown in Table 4:
The stability test result of 4 carnosic acid eye drops of table
(2) long term test: using the 0.3% carnosic acid eye drops by the preparation of 2 method of the embodiment of the present invention in commercially available packet
Under the conditions of dress, it is put into climatic chamber, is placed under conditions of 25 DEG C ± 2 DEG C of temperature, relative humidity 40% ± 5%, respectively at
It samples within 3rd, 6,9,12 month, is measured according to quality standard draft on time.Measurement result is compared with 0 month measurement result, as a result
It is shown in Table 5.
The stability test result of 5 carnosic acid eye drops of table
The result shows that: it is unchanged to save 12 months characters under the conditions of commercially available back for product provided by the invention, it is seen that
Foreign matter meets regulation；In Related substances separation, in relation to content of material without the trend to rise appreciably, does not occur other impurities, contain
It measures fixed, pH value inspection result to have no significant change, sterile to be investigated, equal asepsis growth illustrates rat-tail provided by the invention
Oxalic acid eye drops stability is good.Other example products of the invention have also carried out identical test, and obtain the test of same trend
As a result, being limited by length will not enumerate.
Experimental example 11
The eye irritation of carnosic acid eye drops is tested
Lagophthalmos irritation test is carried out using by 0.5% carnosic acid eye drops of 2 method of embodiment of the present invention preparation.Examination
Test selection 6 healthy new zealand rabbits, half male and half female.Using androgynous left and right branch hole self-contrast method, carnosic acid drop is given in left side
Ocular fluid (administration concentration 0.5mg/ml), each administered volume are 100 μ l, and 50 μ l/ drops, totally 2 drip；Give isometric in right side
0.9% sodium chloride injection compares, and daily administration 5 times, successive administration 28 days.Daily before every 1 administration, the 8th, 15,22 day
About 1 hour after the last administration, the part for observing all animals eyes on the 28th day for 1,2,4 and 24,48,72 hours after the last administration was anti-
Answer the score value of situation and in detail recording exceptional situation and eye reaction, appraisal result be 6/6 animal or so cornea, iris not
See apparent irritation, irritative response score value is 0 point；It is micro- congested existing that iris vessels occur respectively in Some Animals right and left eyes
As, but score value is smaller, is 1 point.It being computed, the score range of the rabbit right eye stimulate the reaction of each observing time point is 0~
0.067；The score value of right and left eyes is in 0~3 point of nonirritant range；Daily before every 1 administration, the 8th, 15,22 day last
About 1 hour after administration, fluorescent staining inspection was carried out to animal eyes in 1,2,4 and 24,48,72 hours after the last administration within the 28th day
It looks into, inspection result is that rabbit eyes are showed no obvious abnormalities variation, and before first administration, the 8th, 15,22 day and the 28th day last is administered
Slit lamp examination is carried out to rabbit eyes and is taken pictures within 72 hours after administration, inspection result is that rabbit eyes are showed no obvious abnormalities change
Change.
The above result shows that by continuous 28 days multiple eye drip (administration concentrations of developed carnosic acid eye drops of the invention
For stoste 0.5mg/ml), lagophthalmos is had no and causes irritative response.Other example products of the invention have also carried out identical examination
It tests, and obtains identical test result, being limited by length will not enumerate.
Experimental example 12
Carnosic acid eye drops tests the protective effect of light injury rat retina form and function
Retinal photic injury in rats is carried out using by 0.3% carnosic acid eye drops of 2 method of embodiment of the present invention preparation
Test.Carnosic acid eye drops of the preparation without ganglioside carries out retinal photic injury in rats test, the eye drops simultaneously
Except ganglioside is free of, other compositions are identical as 0.3% carnosic acid eye drops.SD rat 40,4 groups are randomly divided into, often
Group 10.Respectively normal group, model control group 1, model control group 2, test group 1, test group 2.
All animals of experimental rat are fed one day in the preceding darkroom of illumination, guarantee that specific light source irradiates preceding rat state consistency.
Then it being put into the poly ethylene case (35cm × 30cm × 18cm) with stainless steel wire cover according to grouping, every chest is one group,
Covering all chests with lighttight cloth prevents environment shadow from ringing, and it is small that corresponding light source Continuous irradiation 24 is placed above each chest
When, normal group only carries out darkroom disposal, irradiates without light source.Animal ad lib is intake during irradiation.Irradiation time is early
Morning 9:30 to 9:30 in the next morning, model control group 1 and 1 illumination condition of test group are 10000lux, model control group 2 and test
The intensity of illumination of group 2 is 1000 μ w/cm of ultraviolet light2, each the temperature inside the box is 28 ± 2 DEG C in irradiation process.It is all after the completion of irradiation
The raising of rat darkroom is placed to be influenced by the external world,
Normal group and model control group rat purified water eye drip after modeling, three times a day, 2 drip every time；Test group group uses mouse
Three times a day, 2 drip tail oxalic acid eye drops eye drip every time；7 days after modeling, retina is taken within 14 days to carry out Electronic Speculum and om observation, and
Measure retinal tissue SOD activity and MDA content.
Om observation is as the result is shown: each confluent monolayer cells marshalling of rats in normal control group retina, cell boundaries are clear, shape
State is normal, and gangliocyte color tinted clear is evenly distributed；Each time point inner nuclear layer cell thickness of model control group rat retina
Thinning, gangliocyte missing is more normally organized, the variation degree maximum of 14d after modeling, and with the extension of time after modeling, it is interior
Stratum nucleare thickness, which is presented, continues thinning trend, and gangliocyte missing degree gradually aggravates.Other each cellular layers have thinning phenomenon,
But change compared to inner nuclear layer and ganglion-cell layer, it is still not obvious enough under the microscope in light.The equal calibration of medication group outer nuclear layer thickness
Normal control group is obviously thinning, gangliocyte missing, but degree of injury is significantly lower than model group；With the extension of time after mould,
Substantially reduced using the thinning degree of control group group rat retina outer nuclear layer thickness of carnosic acid eye drops, cell boundaries are compared with mould
Type group is clear, and cellular morphology is more complete, and extends at any time, and each confluent monolayer cells structure change is little, and degree of injury is aggravated without obvious.
(see Fig. 1)
" concept that solar retinopathy becomes " has already appeared in the document in 18th century.Noell is established for the first time within 1966
The animal model of retinal photic injury in rats, and the conclusion that obtains from this model experiment is that photochemical damage damages light at first
Receptor acromere and photoreceptor cell nuclei.Some research reports, duplicate illumination can cause the build-up effect of retinal light damage；And
For a long time, low-intensity, interval solar irradiation may be related with Age related macular change.In electroretinogram (ERG), a wave is represented
The electrical activity of photoreceptor is the initial reaction after light stimulus, is equivalent to the input signal of retina cell；And b wave then represents
The electrical activity of each confluent monolayer cells of retina, is equivalent to outgoing signal；Therefore, a wave depends on the intensity and photoreceptor of light stimulus
Integrality；B wave then depends on the integrality of signal transduction process in a wave and retina.So this experiment uses maximum mixing
The a wave and b wave-amplitude value of reaction are as the index for measuring photochemical damage rat retina function.
All rats are placed in darkroom before detecting, and carry out intraperitoneal injection of anesthesia, fiber crops using 100g/L chloraldurate (4ml/kg)
After liquor-saturated, mydriasis is carried out to rat with Tropicamide eye drops, after with content in tetracaine hydrochloride eye drops to rat carry out eye anesthesia with
And hydroxypropyl first eye drops enhances rat eye electric conductivity.According to order of packets, each group one is detected every time, alternately.With dynamic
Object electrophysiology instrument (ROLAND CONSULT Color Ganzfeld Q450C) detects rat eyes Scotopic 0.01ERG
(GF)。
Normal rats left eye ERG a wave-amplitude be (22.44 ± 4.94) μ V, right eye ERG a wave-amplitude be (22.32 ±
5.48) μ V is handled by the t inspection of paired data, and the two comparing difference is without conspicuousness.Left eye b wave-amplitude be (67.94 ±
2.24) μ V, right eye ERG b wave-amplitude are (67.46 ± 5.33) μ V, are handled by the t inspection of paired data, the two comparing difference
Not significant (P > 0.05)
1d, 7d, 14d after illumination, every group takes 6 rats respectively, totally 12 eyeballs, detects electroretinogram, records respectively
The amplitude of a wave of maximum hybrid reaction, b wave (see Table 6 for details).
1) it Normal group: is examined by paired data t, a, b wave-amplitude value that each time point is normally organized compare two-by-two, poor
Different no significant (P > 0.05).
2) model control group: 1d after mould, a, b wave-amplitude value are remarkably decreased, and profile amplitude, which is more normally organized, substantially to be reduced；After mould
The decline of 7d, a, b wave-amplitude continues, and amplitude is only the 1/4 of the corresponding wave-amplitude value of normal group；14d to 28d after mould, a, b of ERG
Wave-amplitude value continues to decline, and wavy curve, which is presented, extinguishes shape.From entirety, the amplitude of ERG a wave and b wave is more normally organized bright
Aobvious to reduce (P < 0.05), fluctuating range is big, and linear downward trend.
3) test group group: from entirety, medication group a wave and b wave-amplitude value are between model group and normal group, depending on function
It can significant difference (P < 0.05).
Each time point ERG a wave of table 6 and b wave amplitude variations (n=10,)
aP < 0.05, vs Normal group,bP < 0.05, vs model control group
Result of study show carnosic acid eye drops prepared by the present invention to retinal light damage rat and retina
Function and form have protective effect, and the addition of ganglioside significantly enhances the permeability of carnosic acid, keeps drug rapid
It reaches eyeground and reaches effective concentration, effectively inhibit the light injury degree of retina.Other example products of the invention have also carried out phase
Same test, and identical test result is obtained, being limited by length will not enumerate.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (9)
1. a kind of ophthalmic external use medicine compositions, including effective component and auxiliary material, which is characterized in that the effective component includes mouse
Tail oxalic acid；The mass percent that the carnosic acid accounts for described pharmaceutical composition is 0.1~0.5%.
2. pharmaceutical composition according to claim 1, which is characterized in that the effective component further includes ganglioside；
The mass ratio of the ganglioside and the carnosic acid is 1~3:1.
3. pharmaceutical composition according to claim 1 or 2, which is characterized in that the dosage form of described pharmaceutical composition includes drop
Ocular fluid, gel for eye use or spongarion.
4. pharmaceutical composition according to claim 3, which is characterized in that when the dosage form of described pharmaceutical composition is eye drops
Or when gel for eye use, described pharmaceutical composition further includes bacteriostatic agent；The bacteriostatic agent is thimerosal, quaternary ammonium salt bacteriostatic agent, Du
Meter Fen, Xian Bitai, anesin, parabens bacteriostatic agent and three pears acid in any one or more；The bacteriostatic agent with
The mass ratio of the carnosic acid is (0.002~0.5): (0.1~1.0).
5. pharmaceutical composition according to claim 3, which is characterized in that when institute's pharmaceutical composition dosage form be eye drops or
It the use of the pH value that pH adjusting agent adjusts finished product medicament is 5.5~7.0 when gel for eye use；The pH adjusting agent is sodium hydroxide, salt
The minor official acid of acid, sodium citrate, Chinese holly, boric acid, any one or more in borax.
6. pharmaceutical composition according to claim 3, which is characterized in that when the dosage form of institute's pharmaceutical composition is eye drops
When, the auxiliary material includes thickener；The thickener be hydroxypropyl methylcellulose, methylcellulose, sodium hyaluronate, polyvinyl alcohol,
Any one or more of polyvinylpyrrolidone, polycarbophil；The mass ratio of the thickener and the carnosic acid is
(0.1~1.0): (0.1~1.0).
7. pharmaceutical composition according to claim 3, which is characterized in that when the dosage form of institute's pharmaceutical composition is gel for eye use
When, the auxiliary material includes thickener；The thickener be hydroxypropyl methylcellulose, methylcellulose, sodium hyaluronate, polyvinyl alcohol,
Any one or more of polyvinylpyrrolidone, carboxymethyl cellulose, carbomer, chondroitin sulfate, polycarbophil；It is described
The mass ratio of thickener and the carnosic acid is (0.5~5.0): (0.1~1.0).
8. pharmaceutical composition according to claim 3, which is characterized in that when the dosage form of institute's pharmaceutical composition is eye drops
When, it the use of the osmotic pressure molar density that sodium chloride and/or mannitol adjust eye drops finished product medicament is 250~350mOsmol/
kg。
9. pharmaceutical composition according to claim 3, which is characterized in that when the dosage form of institute's pharmaceutical composition is spongarion
When, it further include 8~15 mass parts of wool grease, 2~10 mass of liquid paraffin in the described pharmaceutical composition of every 100 mass parts
Part, 75~90 mass parts of yellow petroleum jelly.
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| CN201910644421.0A CN110200956B (en) | 2019-07-17 | 2019-07-17 | Ophthalmic external medicine composition |
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| CN201910644421.0A CN110200956B (en) | 2019-07-17 | 2019-07-17 | Ophthalmic external medicine composition |
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| CN105193777A (en) * | 2009-01-19 | 2015-12-30 | 利科雷德有限公司 | Synergistic combinations of carotenoids and polyphenols |
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| CN112870216A (en) * | 2021-01-29 | 2021-06-01 | 张宽才 | Pharmaceutical composition, preparation and application |
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