CN110200956B - Ophthalmic external medicine composition - Google Patents
Ophthalmic external medicine composition Download PDFInfo
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- CN110200956B CN110200956B CN201910644421.0A CN201910644421A CN110200956B CN 110200956 B CN110200956 B CN 110200956B CN 201910644421 A CN201910644421 A CN 201910644421A CN 110200956 B CN110200956 B CN 110200956B
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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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Abstract
The invention provides an ophthalmic external medicine composition, and belongs to the field of medical preparations. The ophthalmic external pharmaceutical composition comprises an effective component and an auxiliary material, wherein the effective component comprises carnosic acid; the carnosic acid accounts for 0.1-0.5% of the pharmaceutical composition by mass. The ophthalmic external pharmaceutical composition provided by the invention can treat retinal photo-damage and protect the retina.
Description
Technical Field
The invention relates to the technical field of medical preparations, in particular to an ophthalmic external medicine composition.
Background
Retinal photodamage is a common multiple cause of blindness, and if not treated in time, can cause irreversible vision loss. Many ophthalmologists at home and abroad have conducted a great deal of research on the pathological process, including clinical diagnosis and experimental research, and currently, no ideal treatment scheme exists. Especially, intraocular injection is used for traumatic administration, and repeated injection can greatly increase the incidence rate of infectious endophthalmitis.
Carnosic acid (carnosic acid) is a component of rosemary herb, a chemical formula of C20H28O4Yellow powder with molecular weight of 332.4339 and CAS registry number of 3650-09-7, and antioxidant effectIt is used as food additive or agricultural additive. Gangliosides (GMI) are a class of glycosphingolipids containing sialic acid, which are present in the cell membranes of mammalian cells, particularly neuronal cells, in the highest amounts, and are a natural component of the neuronal cell membrane, GMI, which plays an essential role in neurogenesis, growth and differentiation.
Disclosure of Invention
In view of the technical problems in the background art, the invention aims to provide an ophthalmic external pharmaceutical composition for treating retinal photo-damage and protecting retinal health, which has good local treatment effect, stable property and small toxic and side effects.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an ophthalmic external pharmaceutical composition, which comprises an effective component and an auxiliary material, wherein the effective component comprises carnosic acid; the carnosic acid accounts for 0.1-0.5% of the pharmaceutical composition by mass.
Preferably, the effective component also comprises ganglioside; the mass ratio of the ganglioside to the carnosic acid is 1-3: 1.
preferably, the dosage form of the pharmaceutical composition comprises eye drops, ophthalmic gel or eye ointment.
Preferably, when the dosage form of the pharmaceutical composition is eye drops or ophthalmic gel, the pharmaceutical composition further comprises a bacteriostatic agent; the bacteriostatic agent is one or more of thimerosal, quaternary ammonium salt bacteriostatic agent, domiphen bromide, Xibitai, chlorobutanol, nipagin bacteriostatic agent and triciric acid; the mass ratio of the bacteriostatic agent to the carnosic acid is (0.002-0.5): (0.1-1.0).
Preferably, when the dosage form of the pharmaceutical composition is eye drops or ophthalmic gel, a pH regulator is used for regulating the pH value of the finished medicament to be 5.5-7.0; the pH regulator is any one or more of sodium hydroxide, hydrochloric acid, sodium citrate, citric acid, boric acid and borax.
Preferably, when the dosage form of the pharmaceutical composition is eye drops, the auxiliary material comprises a thickening agent; the thickening agent is any one or more of hydroxypropyl methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone and polycarbophil; the mass ratio of the thickening agent to the carnosic acid is (0.1-1.0): (0.1-1.0).
Preferably, when the dosage form of the pharmaceutical composition is an ophthalmic gel, the adjuvant comprises a thickening agent; the thickening agent is any one or more of hydroxypropyl methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl cellulose, carbomer, chondroitin sulfate and polycarbophil; the mass ratio of the thickening agent to the carnosic acid is (0.5-5.0): (0.1-1.0).
Preferably, when the dosage form of the pharmaceutical composition is eye drops, sodium chloride and/or mannitol are used for adjusting the osmolality of the finished medicament of the eye drops to 250-350 mOsmol/kg.
Preferably, when the dosage form of the pharmaceutical composition is an eye ointment, per 100 parts by mass of the pharmaceutical composition, the pharmaceutical composition further comprises 8-15 parts by mass of anhydrous lanolin, 2-10 parts by mass of liquid paraffin and 75-90 parts by mass of yellow vaseline.
Has the advantages that: the invention provides an ophthalmic external pharmaceutical composition, which comprises an effective component and an auxiliary material, wherein the effective component comprises carnosic acid; the carnosic acid accounts for 0.1-0.5% of the pharmaceutical composition by mass. The ophthalmic external medicinal composition takes carnosic acid as a main medicinal raw material, and has the effects of treating retinal light injury and protecting retinal health.
The invention preferably adds ganglioside liquid on the basis of carnosic acid as the drug effect aid, and is matched with common preparation auxiliary materials to prepare the ophthalmic medicinal preparation. The ganglioside is used for preparing carnosic acid eye preparations, and is helpful for enhancing the effects of carnosic acid in treating retinal damage and protecting retinal health.
In the present invention, the amount of carnosic acid and ganglioside is preferably selected from carnosic acid: ganglioside 1: 1-3, and can be prepared into eye drops, ophthalmic gel, eye ointment, etc., wherein the content of carnosic acid in each 100 weight parts of the medicament is 0.1-0.5 weight part. In addition, except for eye drops, eye gel and eye ointment, the dosage form of the pharmaceutical composition can be any dosage form which is suitable for local external application of eyes in pharmaceutics.
Drawings
FIG. 1 shows the observation results of the optical lens according to example 12 of the present invention.
Detailed Description
The invention provides an ophthalmic external medicine composition which comprises effective components and auxiliary materials. In the present invention, the effective ingredient includes carnosic acid; the carnosic acid is a main drug effect raw material; the carnosic acid accounts for 0.1-0.5% of the pharmaceutical composition by mass, preferably 0.2-0.4% of the pharmaceutical composition by mass, and more preferably 0.25-0.35% of the pharmaceutical composition by mass.
In the present invention, the effective ingredient preferably further includes ganglioside; the mass ratio of the ganglioside to the carnosic acid is preferably 1-3: 1, more preferably 1.2 to 2: 1. the addition of the ganglioside helps to enhance the efficacy of carnosic acid in treating retinal damage and protecting retinal health.
The sources of the carnosic acid and the ganglioside are not particularly limited in the present invention, and any product that meets pharmaceutical standards is commercially available in general in the art.
The invention preferably takes carnosic acid as a pharmacodynamic raw material, adds ganglioside ester as pharmacodynamic assistance, and is matched with common preparation auxiliary materials to prepare the ophthalmic medicinal preparation. In the present invention, the dosage form of the pharmaceutical composition preferably includes eye drops, ophthalmic gel or eye ointment.
In the present invention, when the dosage form of the pharmaceutical composition is eye drops or ophthalmic gel, the pharmaceutical composition preferably further comprises a bacteriostatic agent. The bacteriostatic agent can be any bacteriostatic agent which is known in the pharmacy, and is preferably any one or more of thimerosal, quaternary ammonium salt bacteriostatic agent, domiphen, Xibitai, chlorobutanol, nipagin bacteriostatic agent and tripear acid. The dosage of the bacteriostatic agent is determined according to the conventional dosage in pharmaceutics; for example, 0.002% -0.005% of thimerosal; ② quaternary ammonium salts (including benzalkonium chloride and benzalkonium bromide), domiphen bromide, Xibitai and the like, the effective concentration is 0.002% -0.01%; ③ alcohols, 0.3 to 0.6 percent of chlorobutanol is commonly used; the parabens are usually 0.03-0.06 percent of ethylparaben; acids, such as 0.01-0.08% triciric acid. The concentrations of all the substances are volume-weight percent, namely the substances contain grams per hundred milliliters. In the invention, the mass ratio of the bacteriostatic agent to the carnosic acid is preferably (0.002-0.5): (0.1 to 1.0), more preferably (0.01 to 0.1): (0.1-0.5).
In the invention, when the dosage form of the pharmaceutical composition is eye drops or ophthalmic gel, the pH value of the finished medicament is preferably adjusted to 5.5-7.0, more preferably 6-6.5 by using a pH regulator. The pH regulator is preferably any one or more of sodium hydroxide, hydrochloric acid, sodium citrate, citric acid, boric acid and borax.
In the present invention, when the dosage form of the pharmaceutical composition is eye drops, the adjuvant of the present invention preferably includes a thickener. The thickening agent is preferably any one or more of hydroxypropyl methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone and polycarbophil, and can adopt different polymerization degrees, so that the eye drops reach proper viscosity. In the invention, the mass ratio of the thickening agent to the carnosic acid is preferably (0.1-1.0): (0.1 to 1.0), more preferably (0.1 to 0.3): (0.1-0.5).
In the present invention, when the dosage form of the pharmaceutical composition is an ophthalmic gel, the adjuvant comprises a thickening agent; the thickening agent is any one or more of hydroxypropyl methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl cellulose, carbomer, chondroitin sulfate and polycarbophil; the mass ratio of the thickening agent to the carnosic acid is preferably (0.5-5.0): (0.1 to 1.0), more preferably (2 to 4): (0.1-0.5).
In the present invention, when the pharmaceutical composition is in the form of eye drops, sodium chloride and/or mannitol are preferably used to adjust the osmolality of the finished pharmaceutical preparation of the eye drops to preferably 250 to 350mOsmol/kg, more preferably 280 to 320 mOsmol/kg.
In the invention, when the dosage form of the pharmaceutical composition is the eye ointment, per 100 parts by mass of the pharmaceutical composition, the pharmaceutical composition preferably further comprises 8-15 parts by mass of anhydrous lanolin, 2-10 parts by mass of liquid paraffin and 75-90 parts by mass of yellow vaseline; the mass part of the anhydrous lanolin is more preferably 10-12; the mass part of the liquid paraffin is more preferably 4-8, and more preferably 5-6; the mass part of the yellow vaseline is more preferably 80-85.
In the present invention, the source of each of the above-mentioned adjuvants is not particularly limited, and commercially available products are generally used in the art. The preparation method of each dosage form is not particularly limited, and the required dosage form can be prepared by adopting different auxiliary materials or processes according to different dosage form requirements in the field.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Examples 1 to 3
TABLE 1 EXAMPLES 1-3 raw material components and amounts for preparing carnosic acid eye drops
The preparation method comprises the following steps: dissolving the total amount of carnosic acid with appropriate amount of water for injection, adding ganglioside, stirring for dissolving, dispersing thickener with water for injection, cooling, dissolving pH regulator, osmotic pressure regulator and antibacterial agent with water for injection, stirring, filtering, mixing the two solutions, adding the dissolved mixture of carnosic acid and ganglioside, adding water for injection to full amount, filtering, and packaging. And adjusting the pH value of the finished eye drops to 5.5-7.0 by using a pH regulator.
Examples 4 to 6
TABLE 2 EXAMPLES 4-6 raw material components and amounts for the preparation of carnosic acid ophthalmic gels
The preparation method comprises the following steps: dissolving thickener with water for injection, dispersing, cooling, dissolving pH regulator and bacteriostatic agent with water for injection, dissolving carnosic acid and ganglioside with the solution, adding dissolved thickener, adding water for injection to desired volume, and packaging under aseptic condition.
Examples 7 to 9
TABLE 3 example 7-9 raw material components and amounts for preparing carnosic acid eye ointments
The preparation method comprises the following steps: the eye ointment is prepared by adopting a production method of a pharmaceutically common eye ointment, the carnosic acid and the ganglioside are mixed, a proper amount of sterilized and cooled liquid paraffin is added, the mixture is ground into fine paste, the fine paste is sieved by a 200-mesh sieve, and then a sterile and filtered lanolin and yellow vaseline mixture is gradually added and mixed uniformly to obtain the eye ointment. The preparation apparatus and the packaging container are sterilized.
Experimental example 10
Stability test of carnosic acid eye drops
(1) And (3) accelerated test: the 0.3 percent carnosic acid eye drops prepared by the method of the embodiment 2 of the invention are placed in a constant temperature and humidity box under the condition of commercial package, are placed under the conditions of the temperature of 40 +/-2 ℃ and the relative humidity of 25 +/-5 percent, are sampled at 1 st, 2 rd, 3 th and 6 th months according to time, and are measured according to a quality standard draft. The results are shown in Table 4:
TABLE 4 stability test results for carnosic acid eye drops
(2) And (3) long-term test: the 0.3% carnosic acid eye drops prepared by the method of the embodiment 2 of the invention are placed in a constant temperature and humidity box under the condition of commercial package, are placed under the conditions of the temperature of 25 +/-2 ℃ and the relative humidity of 40 +/-5%, are sampled at 3 rd, 6 th, 9 th and 12 th months according to time, and are measured according to a quality standard draft. The results of the measurement were compared with the results of the measurement at 0 month, and the results are shown in Table 5.
TABLE 5 stability test results for carnosic acid eye drops
The results show that: the product provided by the invention has no change in properties after being stored for 12 months under the condition of commercial package, and visible foreign matters meet the regulations; in the related substance examination, the content of the related substance has no obvious increasing trend, no other impurities appear, the content measurement and pH value examination results have no obvious change, and the content measurement and the pH value examination results are examined aseptically and grow aseptically, which shows that the carnosic acid eye drops provided by the invention have good stability. The other products of the invention were tested in the same way and the results of the tests with the same trend were obtained, which are not listed any more depending on the space.
Experimental example 11
Eye irritation test of carnosic acid eye drops
Rabbit eye irritation tests were performed using 0.5% carnosic acid eye drops prepared according to the method of example 2 of the present invention. 6 healthy New Zealand rabbits, female and male, were selected for the test. Adopting self-contrast method of left and right eyes of the same body, and administering carnosic acid eye drop (administration concentration of 0.5mg/ml) at left side, wherein the administration volume is 100 μ l, 50 μ l/drop, and 2 drops in total; an equal volume of 0.9% sodium chloride injection was given to the right for control, 5 times daily for 28 consecutive days. Before each 1 administration, about 1 hour after 8, 15 and 22 days of the last administration, and 1, 2, 4, 24, 48 and 72 hours after 28 days of the last administration, observing local reaction conditions of eyes of all animals and recording scores of abnormal conditions and eye reactions in detail, wherein the scoring result shows that 6/6 animals have no obvious irritation on the cornea and iris of the left eye and the right eye, and the scores of irritation reactions are 0; the micro hyperemia of iris blood vessels appears in the left eye and the right eye of part of animals, but the score values are small and are 1. Calculating to obtain the values of the right eye irritation responses of the rabbits at all observation time points within the range of 0-0.067; the scores of the left eye and the right eye are both in the nonirritant range of 0-3 points; before every 1 administration, 1 hour after 8, 15 and 22 days of the last administration, and 1, 2, 4, 24, 48 and 72 hours after 28 days of the last administration, the two eyes of the animals are subjected to fluorescein staining examination, the examination result shows that no obvious abnormal change is seen in the two eyes of the rabbits, and the slit lamp examination and the photographing are carried out on the two eyes of the rabbits before the first administration, 8, 15 and 22 days of the administration and 72 hours after 28 days of the last administration, and the examination result shows that no obvious abnormal change is seen in the two eyes of the rabbits.
The results show that the carnosic acid eye drops prepared according to the invention can be applied in eye drops for 28 consecutive days (the administration concentration is 0.5mg/ml of the stock solution), and do not cause irritation reaction to rabbit eyes. The other products of the invention were tested in the same way and the same results were obtained, which are not listed any more depending on the space.
Experimental example 12
Test for protective effect of carnosic acid eye drops on shape and function of retina of rat with light injury
Rat retina light injury tests were performed using 0.3% carnosic acid eye drops prepared according to the method of example 2 of the present invention. Meanwhile, carnosic acid eye drops without ganglioside ester are prepared for rat retina light injury test, and the components of the eye drops are the same as the 0.3 percent carnosic acid eye drops except that the eye drops do not contain ganglioside ester. SD rats 40, randomly divided into 4 groups of 10. Respectively a normal group, a model control group 1, a model control group 2, a test group 1 and a test group 2.
All animals of the experimental rat were fed in the dark for one day before the light irradiation to ensure the specific light sourceThe rat status before shooting was consistent. Then putting the materials into polyethylene boxes (35cm multiplied by 30cm multiplied by 18cm) with stainless steel wire covers according to groups, covering all the boxes by using light-tight cloth to prevent the influence of ambient light, placing corresponding light sources above each box to continuously irradiate for 24 hours, and only carrying out darkroom treatment and not carrying out light source irradiation on the normal groups. During irradiation the animals were free to feed into the water. The irradiation time was 9 a.m.: 30 to the next morning 9: 30, the illumination conditions of the model control group 1 and the test group 1 are 10000lux, and the illumination intensity of the model control group 2 and the test group 2 is ultraviolet light 1000 muw/cm2The temperature in each chamber during irradiation is 28 +/-2 ℃. After the irradiation is finished, all rats are raised and placed in a dark room and are influenced by the outside,
after modeling, rats in the normal group and the model control group are dropped with purified water, 3 times a day, 2 drops each time; the test group had carnosic acid eye drops applied 3 times a day, 2 drops each time; and (3) taking retinas 7 days and 14 days after the model building, observing the retinas by an electron microscope and a light microscope, and determining the SOD activity and the MDA content of the retinal tissues.
The observation result of the light lens shows that: the normal control group rat retina cells in all layers are arranged regularly, the cell boundary is clear, the shape is normal, the ganglion cells are colored clearly and distributed uniformly; the thickness of the inner nuclear layer cells of the rat retina of the model control group is thinner than that of the normal group at each time point, the ganglion cells are deleted, the change degree of 14d after modeling is the largest, the thickness of the inner nuclear layer shows the continuous thinning trend along with the prolonging of the time after modeling, and the deletion degree of the ganglion cells is gradually increased. Other cell layers are thinned, but the change of the cell layers is not obvious enough when observed under a light microscope compared with the change of an inner nuclear layer and a nerve node cell layer. The thickness of the outer nuclear layer of the used medicine group is obviously thinner than that of the normal control group, ganglion cells are deleted, but the damage degree is obviously lower than that of the model group; along with the time after the model is prolonged, the thinning degree of the outer nuclear layer of the retina of the rat in the control group using the carnosic acid eye drops is obviously reduced, the cell boundary is clearer than that of the model group, the cell form is more complete, the cell structure of each layer is not changed greatly along with the time extension, and the damage degree is not obviously aggravated. (see FIG. 1)
The concept of "solar retinopathy" has emerged in the literature in the 18 th century. Noell first established an animal model of rat retinal photodamage in 1966, and concluded from this model experiment that photochemical damage first damaged photoreceptor outer segment and outer nuclear layer cells. Some studies report that repeated light exposure can cause cumulative effects of retinal photodamage; whereas long-term, low-intensity, intermittent solar radiation may be associated with age-related macular degeneration. In Electroretinograms (ERGs), the a-wave represents the electrical activity of the photoreceptors, and is the initial response to light stimulation, corresponding to the afferent signals of the retinal cells; the b wave represents the electrical activity of cells in each layer of the retina, and is equivalent to an efferent signal; thus, the a-wave depends on the intensity of the light stimulus and the integrity of the photoreceptors; the b-wave depends on the integrity of the a-wave and the intra-retinal signaling process. Therefore, the amplitude values of the a wave and the b wave of the maximum mixed reaction are adopted as indexes for measuring the function of the retina of the rat with photochemical damage in the experiment.
Before detection, all rats are placed in a dark room, 100g/L chloral hydrate (4ml/kg) is used for intraperitoneal injection anesthesia, after anesthesia, the rats are mydriasis is carried out by topiramide eye drops, then the rats are subjected to eye anesthesia by tetracaine hydrochloride eye drops, and the conductivity of the rat eyes is enhanced by hydroxypropyl methyl eye drops. According to the grouping sequence, one of each group is detected at a time, and the detection is performed alternately. Scotopic 0.01ERG (GF) was detected in both eyes of rats by an animal electrophysiology instrument (ROLAND CONSULT Color Ganzfeld Q450C).
The left eye ERG a wave amplitude of the rats in the normal group is (22.44 +/-4.94) muV, the right eye ERG a wave amplitude is (22.32 +/-5.48) muV, and the comparison of the left eye ERG a wave amplitude and the right eye ERG a wave amplitude is not significant after the t test treatment of paired data. The left eye b wave amplitude is (67.94 +/-2.24) mu V, the right eye ERG b wave amplitude is (67.46 +/-5.33) mu V, and the two are not significantly different (P >0.05) after the t test treatment of matched data
After 1d, 7d and 14d of illumination, 6 rats in each group with 12 eyeballs are taken respectively, electroretinograms are detected, and the amplitudes of a wave and b wave of the maximum mixed reaction are recorded respectively (see table 6 for details).
1) Normal control group: and through the matching data t test, the amplitude values of the a wave and the b wave of the normal group at each time point are compared pairwise, and the difference has no significance (P is more than 0.05).
2) Model control group: the amplitude values of a and b waves are obviously reduced 1d after the model, and the curve amplitude is greatly reduced compared with that of a normal group; 7d, after the model, the amplitude of the a wave and the b wave is reduced continuously, and the amplitude value is only 1/4 of the amplitude value of the corresponding wave of the normal group; from 14d to 28d after the mode, the amplitude values of the a wave and the b wave of the ERG continue to decline, and the wave curve is extinguished. From the overall view, the amplitude values of the ERG a wave and the ERG b wave are both obviously reduced (P <0.05) compared with the normal group, the fluctuation range is large, and the linear descending trend is realized.
3) Test group: in the overall view, the amplitude values of the a wave and the b wave of the drug group are between those of the model group and the normal group, and the difference of the visual function is obvious (P < 0.05).
Table 6 the ERG a and b waves at each time point varied in amplitude (n 10,
)
aP<0.05, vs normal control group,bP<0.05, vs model control group
Research results show that the carnosic acid eye drops prepared by the invention have a protective effect on retinal function and form of a rat with retinal photodamage, and the addition of the ganglioside significantly enhances the permeability of carnosic acid, so that the medicine can quickly reach the fundus to reach an effective concentration, and the photodamage degree of the retina is effectively inhibited. The other products of the invention were tested in the same way and the same results were obtained, which are not listed any more depending on the space.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (9)
1. An ophthalmic external pharmaceutical composition comprises an effective component and an auxiliary material, and is characterized in that the effective component comprises carnosic acid; the carnosic acid accounts for 0.1-0.5% of the pharmaceutical composition by mass;
the effective component also comprises ganglioside.
2. The pharmaceutical composition of claim 1, wherein the weight ratio of the ganglioside to the carnosic acid is 1-3: 1.
3. the pharmaceutical composition of claim 1 or 2, wherein the pharmaceutical composition is in a dosage form comprising eye drops, ophthalmic gel or eye ointment.
4. The pharmaceutical composition of claim 3, wherein when the pharmaceutical composition is in the form of eye drops or an eye gel, the pharmaceutical composition further comprises a bacteriostatic agent; the bacteriostatic agent is one or more of thimerosal, quaternary ammonium salt bacteriostatic agent, domiphen bromide, chlorhexidine, chlorobutanol, nipagin bacteriostatic agent and sorbic acid; the mass ratio of the bacteriostatic agent to the carnosic acid is (0.002-0.5): (0.1-1.0).
5. The pharmaceutical composition of claim 3, wherein when the pharmaceutical composition is in the form of eye drops or eye gel, the pH value of the finished pharmaceutical product is adjusted to 5.5-7.0 by using a pH regulator; the pH regulator is any one or more of sodium hydroxide, hydrochloric acid, sodium citrate, citric acid, boric acid and borax.
6. The pharmaceutical composition of claim 3, wherein when the pharmaceutical composition is in the form of eye drops, the excipient comprises a thickening agent; the thickening agent is any one or more of hydroxypropyl methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone and polycarbophil; the mass ratio of the thickening agent to the carnosic acid is (0.1-1.0): (0.1-1.0).
7. The pharmaceutical composition of claim 3, wherein when the pharmaceutical composition is in the form of an ophthalmic gel, the excipient comprises a thickening agent; the thickening agent is any one or more of hydroxypropyl methylcellulose, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone, carboxymethyl cellulose, carbomer, chondroitin sulfate and polycarbophil; the mass ratio of the thickening agent to the carnosic acid is (0.5-5.0): (0.1-1.0).
8. The pharmaceutical composition of claim 3, wherein when the pharmaceutical composition is in the form of eye drops, sodium chloride and/or mannitol are used to adjust the osmolality of the finished pharmaceutical formulation of the eye drops to 250-350 mOsmol/kg.
9. The pharmaceutical composition according to claim 3, wherein when the pharmaceutical composition is in the form of an eye ointment, the pharmaceutical composition further comprises 8 to 15 parts by mass of anhydrous lanolin, 2 to 10 parts by mass of liquid paraffin, and 75 to 90 parts by mass of yellow vaseline, per 100 parts by mass of the pharmaceutical composition.
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