CN108125996A - It is a kind of for visual fatigue, dry eyes eye-drops preparations - Google Patents
It is a kind of for visual fatigue, dry eyes eye-drops preparations Download PDFInfo
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- CN108125996A CN108125996A CN201711364951.7A CN201711364951A CN108125996A CN 108125996 A CN108125996 A CN 108125996A CN 201711364951 A CN201711364951 A CN 201711364951A CN 108125996 A CN108125996 A CN 108125996A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
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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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
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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
Abstract
The invention discloses a kind of for visual fatigue, the eye-drops preparations of dry eyes, comprising medical composite for eye, Moringa flavones is included in the ophthalmic composition.Moringa flavones is applied to eye-drops preparations by the present invention, Moringa flavones has good intraocular penetration, intraocular bioavilability is higher, the advantages that penetration is strong, targeting is strong, toxic side effect is small, can effectively prevent the endogenous illness such as xerophthalmia scheorma syndrome, this about two Cotards, ophthalmoxerosis and various external cause illness (as after operation, Drug, wound, contact lens wear etc.) caused by conjunctival epithelium damage, and raw material is easy to get, it is at low cost, it can realize industrialization large-scale production, there is significant economic benefit.
Description
Technical field
The present invention relates to a kind of eye-drops preparations, and in particular to a kind of for visual fatigue, the eye-drops preparations of dry eyes.
Background technology
Due in the modern life, the work and amusement of young people contact more and more with TV, computer, long-time face
To fluorescent screen, excessively reading and contact glasses is universal, and it is more older more that obstacle crowd occurs in eye microcirculation.Eye is micro-
There is obstacle and has blurred vision in cycle, and periocualr skin blacks, and sees the symptoms such as dizzy, headache during thing, usually reads a book the time slightly
Length can feel that eye is puckery, eye is swollen, tired, and early stage often will appear livid ring around eye, with seeing that thing feels that eye is puckery, the symptoms such as uncomfortable often.
Xerophthalmia is also known as angle xerosis of conjunctiva, tear matter caused by xerophthalmia refers to any reason or amount exception or power
Exception is learned, tear film stability is caused to decline, and with the total of a variety of diseases of ophthalmic uncomfortable and (or) ocular lesion tissue feature
Claim.Common symptom includes dry and astringent, the easy tired, eye of eyes and itches, has sticky foreign body sensation, pain burning heat sensation, secretion, fear of wind, fear
It is light, very sensitive to environmental stimuli；Sometimes eyes are too dry, basic oligodacrya, stimulate reflectivity lacrimal secretion instead, and cause
Usually shed tears；More severe case eyes can redness, hyperemia, keratinization, corneal epithelium broken skin and there is filiform to stick, this damage
With the passing of time angle conjunctive disorder can be then caused, and can be affected vision.Research is thought recently, the change of eye surface, based on immune inflammation
Reaction, the change etc. of Apoptosis, sex hormone level are the correlative factors of xerophthalmia occurrence and development.
Invention content
It is provided a kind of for visual fatigue, dry eyes it is an object of the invention to overcome the shortcomings of the prior art part
Eye-drops preparations.
To achieve the above object, the technical solution taken：A kind of medical composite for eye includes Moringa flavones.
Moringa (Moringa oleifera Lam), belong to Moringaceae Moringa platymiscium, be distributed widely in Asia, Africa
Subtropical and tropical zones.Moringa contains abundant protein, vitamin, amino acid, fat and carbohydrate, root,
Stem, leaf, fruit, bark etc. often are used to treat various diseases, therefore are otherwise known as " tree of miracle ".Moringa flavones is Moringa master
The active constituent wanted has a variety of physiological activity such as anti-oxidant, antitumor, and some researches show that Moringa flavones can be substantially reduced sugar
The blood glucose of disease model mouse is urinated, while serum activity of SOD can be improved, reduces Content of MDA, is had in medicines and health protection industry
Have wide practical use.Moringa flavones is applied to eye-drops preparations by the present invention, and Moringa flavones has good intraocular penetration
The advantages that property, intraocular bioavilability is higher, and penetration is strong, targeting is strong, toxic side effect is small, eye can be effectively prevented
The endogenous such as dry syndrome, ectodermosis pluriorificialis, ophthalmoxerosis illness and various external cause illness (as after performing the operation, drug
Property, wound, contact lens wear etc.) caused by conjunctival epithelium damage, and raw material is easy to get, at low cost, can realize industrialization
Large-scale production has significant economic benefit.
As the preferred embodiment of medical composite for eye of the present invention, the medical composite for eye also includes
Sodium hyaluronate, vitamin E and chondroitin sulfate；The Moringa flavones, sodium hyaluronate, vitamin E and chondroitin sulfate weight
The ratio between be：Moringa flavones：Sodium hyaluronate：Vitamin E：Chondroitin sulfate=1：(0.15~1)：(0.2~10)：(0.02~
0.2)。
Sodium hyaluronate (Sodium Hyaluronate) also known as Sodium Hyaluronate, be by N- acetyl glucosamines aldehydic acid repeatedly
A kind of macromolecule polysaccharide body biomaterial alternately formed.Sodium hyaluronate is the main component of knuckle synovia, is cartilage matrix
One of ingredient.Sodium hyaluronate has significant hydrophilic ability and lubricating action, therefore, can obviously relieve the pain of ophthalmoxerosis
Bitterly, itch, burn feeling, the clinical symptoms such as foreign body sensation, hence it is evident that extend breakup time of tear film.
Chondroitin sulfate (CS) is to be covalently attached a kind of glycosaminoglycan that proteoglycans is formed on protein, corneal
Collagenous fibres have protective effect, can promote the growth of fiber in matrix, enhance permeability, improve blood circulation, accelerate new old
Metabolism, promotes the absorption of penetrating fluid and the elimination of inflammation；Its polyanion has strong water-retaining property, can improve corneal tissue
Water metabolism, corneal has stronger affinity, can form one layer of ventilative water-retaining film in anterior corneal surface, improve eye dryness
Symptom.By promoting the generation of matrix, the migration for cell provides framework, is conducive to the migration of corneal epithelial cell, so as to promote
Into the healing of corneal wound, the absorption of diffusate and the elimination of inflammation.
Vitamin E (Vitamin E) is a kind of liposoluble vitamin, and hydrolysate is tocopherol, is most important anti-
One of oxidant, vitamin E can inhibit the lipid peroxidation reaction in ocular lens body, make peripheral vasodilation, improve blood and follow
Ring.
Moringa flavones, sodium hyaluronate, vitamin E and chondroitin sulfate are used cooperatively by the present invention, are especially matched above-mentioned
Than under so that medical composite for eye of the present invention have it is anti-inflammatory, remove oxidation product, be obviously prolonged breakup time of tear film
The effects that.
As the more preferable embodiment of pharmaceutical composition of the present invention, the Moringa flavones, sodium hyaluronate, dimension life
The weight ratio of plain E and chondroitin sulfate is：Moringa flavones：Sodium hyaluronate：Vitamin E：Chondroitin sulfate=1：(0.3~
0.5)：(1~5)：(0.05~0.1).
Through inventor's test of many times the study found that when Moringa flavones, sodium hyaluronate, vitamin E and chondroitin sulfate are upper
It states and is used cooperatively under proportioning, described pharmaceutical composition is dry and astringent to eyes and visual fatigue has better effect.
As the preferred embodiment of medical composite for eye of the present invention, the dosage form of the medical composite for eye
For eye drops, gel for eye use or spongarion.
As the preferred embodiment of medical composite for eye of the present invention, in the eye drops, gel for eye use or eye
In ointment, the Moringa flavones content is 0.1~2g/100mL.
When Moringa flavones is above-mentioned additive amount in the eye drops, gel for eye use or spongarion, can preferably it play peppery
The utilization ratio of the effect of genitein and Moringa flavones is higher.
It is described medicinal auxiliary also comprising pharmaceutic adjuvant as the preferred embodiment of medical composite for eye of the present invention
Material includes bacteriostatic agent, osmotic pressure regulator, pH adjusting agent, thickener, cosolvent, Chinese herbs material, atoleine and Huang Fanshi
At least one of woods.
Described pharmaceutical composition can add some such as bacteriostatic agents, osmotic pressure regulator, pH adjusting agent, thickener, help
The pharmaceutic adjuvant of solvent, Chinese herbs material, atoleine and yellow petroleum jelly etc. is prepared into different dosage forms.Ophthalmic external use medicine object
It needs to reach a series of particular requirements：It is 1. antibacterial：Most of eye-drops preparations need to reuse because being multiple-unit container, use
Easily contaminated in the process, so to add bacteriostatic agent, pathogen can be killed or inhibited its growth, breeding by bacteriostatic agent；②
Suitable acid-base value：The eye drops that pH is 7.4 is minimum to the irritation of eyes, without uncomfortable sensation, normal eyes when pH is 6~8
Tolerable pH is 5~9, and has apparent irritation if pH ＜ 5 or pH ＞ 11.4, and therefore, it is necessary to maintain Moringa flavones
Under the premise of, the suitable pH value of adjustment liquid；3. suitable osmotic pressure：The osmotic pressure of eye drops should be close with tear, quite
In 0.9% sodium chloride solution.For eyes in the case of no wound, adaptable osmolarity ranges are equivalent to 0.6~2.0%
Sodium chloride solution, osmotic pressure is excessively high to be dehydrated eye, and osmotic pressure is too low to make ocular edema, hyperosmosis or Hyposmolality
Lacrimal secretion can be also stimulated, eye drops is diluted and rushes Xian to fall；4. suitable viscosity：The viscosity relationship of eye-drops preparations is to drug
Residence time, drug bioavailability in conjunctival sac and the irritation to eye are viscous selected by adjustment formulation viscosity
Thick dose will have suitable light transmittance, index of refraction；5. formula and technique：It is anti-that with Moringa flavones physics and chemistry does not occur for pharmaceutic adjuvant used
Should, it affects the treatment；Auxiliary material used is conducive to the stabilization of Moringa flavones, and preparation is enable to preserve for a long time；Prescription and preparation process will protect
It demonstrate,proves in preparation without visible foreign matters；To eye low irritant, tear is avoided largely to secrete.
The bacteriostatic agent can use so-called any bacteriostatic agent in pharmacy, and dosage is by routine dose in pharmacy.
Such as, 1. 0.002~0.005g/mL thimerosals；2. quaternary ammonium salt (including benzalkonium chloride, benzalkonium bromide), Domiphen, Xian Bitai
It is 0.002~0.01g/mL Deng, effective concentration；3. alcohols commonly uses 0.3~0.6g/mL anesins；4. parabens, often
With 0.03~0.06g/mL ethyl hydroxy benzoates；5. acids, such as 0.01~0.08g/mL, tri- pears acid.As ophthalmically acceptable medicine of the present invention
The preferred embodiment of compositions, the bacteriostatic agent for thimerosal, quaternary ammonium salt, Domiphen, Xian Bitai, anesin,
At least one of parabens and three pears acid；
Common thickener in pharmacy may be used in the thickener, such as hydroxypropyl methylcellulose, methylcellulose, gathers
At least one of vinyl alcohol, polycarbophil and polyvinylpyrrolidone；Different polymerization degree can be used, finally reach eye drops
To suitable viscosity.
As the preferred embodiment of medical composite for eye of the present invention, the osmotic pressure regulator is sodium chloride
And/or mannitol；The pH adjusting agent is at least one in sodium hydroxide, hydrochloric acid, sodium citrate, the minor official acid of Chinese holly, boric acid and borax
Kind；The cosolvent is Tween-80 and/or rilanit special.
In addition to pharmaceutic adjuvant necessary to eye-drops preparations is added, some Chinese herbs materials can also be added, to enhance Moringa
The effect of flavones eye-drops preparations, reduce side effect the effect of, the Chinese herbs material include astragalus polyose, Qing kailing, borneol,
At least one of cordate houttuynia and Radix Isatidis.
As the preferred embodiment of medical composite for eye of the present invention, in the eye drops or gel for eye use,
The weight ratio of the bacteriostatic agent and Moringa flavones is：Bacteriostatic agent：Moringa flavones=(0.002~1)：1；The thickener with
The weight ratio of Moringa flavones is：Thickener：Moringa flavones=(0.02~1)：1.
As the preferred embodiment of medical composite for eye of the present invention, in the eye drops, osmol(e)
A concentration of 250~350mOsmol/kg.
As the preferred embodiment of medical composite for eye of the present invention, in the eye drops, the pH value is
5.5~7.5.
As the preferred embodiment of medical composite for eye of the present invention, the dosage form of the medical composite for eye
For eye drops, contain 1g Moringas flavones, 0.25g sodium hyaluronates, 5g vitamin Es, 0.2g sulfuric acid per 100mL in the eye drops
Chondroitin, 0.2g bacteriostatic agents, 0.2g osmotic pressure regulators, 0.1g thickeners, 0.5g pH adjusting agents, 0.1g cosolvents and surplus
Water.
As the preferred embodiment of medical composite for eye of the present invention, the dosage form of the medical composite for eye
For gel for eye use, contain 1g Moringas flavones, 0.5g sodium hyaluronates, 5g vitamin Es, 0.1g sulphur per 100mL in the gel for eye use
Aching and limp ossein, 0.02g bacteriostatic agents, 0.2g osmotic pressure regulators, 0.05g thickeners, 0.5g pH adjusting agents, 0.1g cosolvents and
The water of surplus.
As the preferred embodiment of medical composite for eye of the present invention, the dosage form of the medical composite for eye
For spongarion, the spongarion includes the component of following parts by weight：1 part of Moringa flavones, 0.3~0.5 part of sodium hyaluronate, dimension life
Plain 1~5 part of E, 0.05~0.1 part of chondroitin sulfate, 8~15 parts of wool grease, 2~10 parts of liquid paraffin and yellow petroleum jelly
75~96 parts.
Another object of the present invention, which also resides in, provides a kind of purposes of above-mentioned medical composite for eye in medicine preparation,
The drug is used for after preventing xerophthalmia, ectodermosis pluriorificialis or alleviating dry and astringent eyes, visual fatigue or prevention operation, medicine
Conjunctival epithelium damage caused by physical property, wound, contact lens wear.
The beneficial effects of the present invention are：It is of the invention by Moringa flavones the present invention provides a kind of medical composite for eye
Applied to eye-drops preparations, Moringa flavones has good intraocular penetration, and intraocular bioavilability is higher, and penetration is strong, targeting
The advantages that effect is strong, toxic side effect is small, can effectively prevent xerophthalmia scheorma syndrome, ectodermosis pluriorificialis, ophthalmoxerosis
Wait endogenous illness and various external cause illness (as after performing the operation, Drug, wound, contact lens wear etc.) caused by angle conjunctiva
Epithelial damage, and raw material is easy to get, it is at low cost, it can realize industrialization large-scale production, there is significant economic benefit.
Specific embodiment
To better illustrate the object, technical solutions and advantages of the present invention, below in conjunction with specific embodiment to the present invention
It is described further.
Embodiment 1
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is eye drops, and formula is shown in Table 1.
The preparation method of eye drops described in the present embodiment includes the following steps：
(1), it is swollen recipe quantity sodium hyaluronate 2~4 hours with appropriate water for injection, is first added in and helped with a small amount of water for injection
Solvent adds Moringa flavones, vitamin E and chondroitin sulfate, adds in sodium hyaluronate solution after swelling after stirring and dissolving, stir
Mix uniform A liquid；
(2), it is cooled to room temperature its dispersion thickener and cosolvent water for injection, obtains B liquid；
(3), with water for injection solution pervasion pressure conditioning agent, bacteriostatic agent and Chinese herbs material, filtering is stirred evenly, obtains C liquid；
(4), B, C liquid are mixed, adds A liquid, it is 5.5~7.5 to adjust pH value, is added to the full amount of water for injection, and is filtered,
Up to eye drops described in the present embodiment.
Embodiment 2
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is eye drops, and formula is shown in Table 1.
The preparation method is the same as that of Example 1 for eye drops described in the present embodiment.
Embodiment 3
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is eye drops, and formula is shown in Table 1.
The preparation method is the same as that of Example 1 for eye drops described in the present embodiment.
The formula (unit g/100mL) of eye drops described in 1 Examples 1 to 3 of table
Embodiment 4
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is gel for eye use, and formula is shown in Table 2.
The preparation method of gel for eye use described in the present embodiment includes the following steps：
(1), it is swollen recipe quantity sodium hyaluronate 2~4 hours with appropriate water for injection, is first added in and helped with a small amount of water for injection
Solvent adds Moringa flavones, vitamin E and chondroitin sulfate, adds in sodium hyaluronate solution after swelling after stirring and dissolving, stir
Mix uniform A liquid；
(2), it is cooled to room temperature its dispersion thickener and cosolvent water for injection, obtains B liquid；
(3), with water for injection solution pervasion pressure conditioning agent, bacteriostatic agent and Chinese herbs material, filtering is stirred evenly, obtains C liquid；
(4), B, C liquid are mixed, adds A liquid, it is 5.5~7.5 to adjust pH value, is added to the full amount of water for injection, and is filtered,
Up to gel for eye use described in the present embodiment.
Embodiment 5
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is gel for eye use, and formula is shown in Table 2.
The preparation method of gel for eye use described in the present embodiment is the same as embodiment 4.
Embodiment 6
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is gel for eye use, and formula is shown in Table 2.
The preparation method of gel for eye use described in the present embodiment is the same as embodiment 4.
The formula (unit g/100mL) of 2 embodiment of table, 4~6 gel for eye use
Embodiment 7
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is spongarion, and formula is shown in Table 3.
The preparation method of spongarion described in the present embodiment is as follows：With appropriate water for injection swelling recipe quantity sodium hyaluronate 2~
4 hours, Moringa flavones, vitamin E and chondroitin sulfate are added in a small amount of water for injection, after adding in swelling after stirring and dissolving
Sodium hyaluronate solution adds required Chinese herbs material, adds in appropriate sterilized, cooling liquid paraffin, is ground into thin paste
Shape, cross 200 mesh sieve, then be gradually added into it is sterile, filtration lanolin, yellow petroleum jelly mixture, mixing to get.Preparing device used
Tool and packing container must sterilize.
Embodiment 8
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is spongarion, and formula is shown in Table 3.
The preparation method of spongarion described in the present embodiment is the same as embodiment 7.
Embodiment 9
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is spongarion, and formula is shown in Table 3.
The preparation method of spongarion described in the present embodiment is the same as embodiment 7.
The formula of 3 embodiment of table, 7~9 spongarion
Embodiment 10
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is eye drops, the formula of eye drops described in the present embodiment and the content that the difference is that only Moringa flavones of embodiment 1
Difference, the content of Moringa flavones is 0.5g/100mL in the present embodiment.
Embodiment 11
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is eye drops, the formula of eye drops described in the present embodiment and the content that the difference is that only Moringa flavones of embodiment 1
Difference, the content of Moringa flavones is 1g/100mL in the present embodiment.
Embodiment 12
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is eye drops, the formula of eye drops described in the present embodiment and the content that the difference is that only Moringa flavones of embodiment 1
Difference, the content of Moringa flavones is 1.5g/100mL in the present embodiment.
Embodiment 13
A kind of embodiment of medical composite for eye of the present invention, the agent of medical composite for eye described in the present embodiment
Type is eye drops, the formula of eye drops described in the present embodiment and the content that the difference is that only Moringa flavones of embodiment 1
Difference, the content of Moringa flavones is 2g/100mL in the present embodiment.
Comparative example 1
A kind of comparative example of medical composite for eye of the present invention, the agent of medical composite for eye described in this comparative example
Type is eye drops, the formula of eye drops described in this comparative example and the difference that the difference is that only Moringa flavones of embodiment 1,
This comparative example is free of Moringa flavones, and Moringa flavones is replaced using the water for injection of equivalent.
Embodiment 14
The pharmacokinetic trial of ophthalmic applications is done using eye drops described in embodiment 2：
With healthy new zealand rabbit (half male and half female) for experimental animal, carry out after single-dose and after multiple dosing respectively
Aqueous humor detects.
Single-dose：20 after administration, 40,60,80,100,120,150,210,270,360,480min extract
30 μ l of aqueous humor are detected；
Multiple dosing is successive administration 7 days, daily administration 4 times, and every 6 hours primary.Last 1 administration at the 6th day respectively
Before, the 7th day the 1st time and the 2nd time administration before take 30 μ l of aqueous humor detect；Respectively at the 7th day the 3rd time administration after 20,40,60,80,
100th, 120,150,210,270,360,480min extracts 30 μ l of aqueous humor detections, and Aqueous humor samples are measured through LC-MS.
The C of Moringa flavones in single-dose aqueous humormaxFor 35.80 ± 9.52mg/ml；TmaxIt is 45.11 ± 11.45
min；T1/2For 80.42 ± 14.50min；AUC0-tFor 5074.11 ± 957.11mgminmL-1, AUC0-$It is 5470.11
±1159.88mg·min·mL-1；Ke is 0.01 ± 0.001min-1.After multi-dose eye drop administration, Moringa flavones in aqueous humor
TmaxFor 56.00 ± 14.20min；T1/2For 79.46 ± 13.02min, KeFor 0.01 ± 0.001 min-1, AUC0-tIt is 6010.50
±1428.11mg·min·mL-1, AUC0-$For 6086.50 ± 1124.50 mgminmL-1, Css maxFor 45.44 ±
11.25mg·mL-1, Css minFor 2.7 ± 0.65mgmL-1, CavgFor 10.74 ± 2.54mgmL-1, FI (%) is 95.8%
± 8.7%.Compare multi-dose and the pharmacokinetic parameter of single dose administration, Ke, T1/2Difference on not statistically significant, table
The release rate substantially constant of the Moringa flavones ophthalmic administration of bright two dosage, does not change with successive administration.The fluctuation hundred of drug
Score is larger, Css minIt is very low, it was demonstrated that Moringa flavones is not accumulated substantially in aqueous humor.Single dose and multiple dose administration main medicine generation
The comparison of kinetic parameter is shown in Table 4.
4 single dose of table and multiple dose administration main pharmacokinetic parameter
The preparation of tissue samples：Animal is put to death with gas embolism method after single dose administration, then strikes off cornea with blade
Epithelium, normal saline flushing conjunctival sac extract aqueous humor, the moisture of conjunctival sac are blotted with cotton swab, with micro- clip part chou
Then with normal saline flushing, 1.5ml is placed on after filter paper suck dry moisture for film, cornea, iris, retina, vitreum and sclera
It in test tube, closes the lid, is placed on scales/electronic balance weighing as early as possible, be then transferred into 8ml teat glass, add methylene chloride 5ml,
Tissue is fully crushed with microscissors.With centrifuge after ten minutes, bottom dichloromethane 4.5ml is taken in another test tube, is used
Nitrogen dries up.Closed test tube mouth, in 4 DEG C of preservations.Compare ophthalmically acceptable same method processing.
Experiment shows that Moringa flavones is distributed widely in each Main Tissues of intraocular, with concentration in conjunctiva, cornea and iris most
It is high.The distributed density of eye Main Tissues is shown in Table 5 after eye drops single dose administration described in embodiment 2.
The distributed density of eye Main Tissues after the administration of 5 Moringa flavones eye drops single dose of table
Table 5 the result shows that, using the eye drops single dose and multiple dose eye drip prepared by the method for the present invention, intraocular is each
Moringa flavones concentration in Main Tissues is all higher, especially with concentration highest in conjunctiva, cornea and iris, illustrates the present invention
Eye drops intraocular penetration it is good, concentration is high, for prevent intraocular noninfectious disease fully achieve effectively treat it is dense
Degree.
Embodiment 15
Eye-drops preparations prepared by pharmaceutical composition of the present invention is mainly used for dry eyes, therefore to observe its right for the present embodiment
Lachrymal gland injecting atropine makes the effect of xerophthalmia Rabbit Model, and (does not add Moringa flavones, other components with comparative example 1
It is same as Example 1) and the progress pharmacodynamics comparison of commercially available 0.1% sodium hyaluronate eye drops.
Using eye drops described in embodiment 1 as trial target；Made using comparative example 1, commercially available 0.1% sodium hyaluronate eye drops
For positive reference substance, observe the eye drops of the flavones of Moringa containing 0.1g/mL described in embodiment 1 to the treatment of rabbit dry eye model eye and
Improvement result.
Regular grade new zealand rabbit 40 (80), half male and half female, eyes drip 1% atropine sulfate ophthalmic solution, 1% sulphur
Sour atropine eye drops eye drip when 8,12,16,20 daily, 1~2 drop, induces rabbit dry eye model eye every time.Random choosing
10 rabbits are treated, 3 times a day, 2 drop, is used continuously 14d every time, is real as A groups using eye drops described in embodiment 1
Test group；It is random that 10 rabbits is selected to be treated as B groups using eye drops described in comparative example 1,3 times a day, 2 drip every time, continuously
Using 14d, as a control group 1；It is random to select 10 rabbits as C groups, using 0.1% sodium hyaluronate eye drops, 2 times a day, every time
2 drops are control group 2.2.5gL is given once daily with control animals eyes in experimental group-1Chloromycetin eyedrops anti-infective therapy,
1 time a day, every time 2 drop, be used continuously 14d.Result of study is as follows：
1st, eye is observed
After treatment group animal gives Moringa flavones eye drops, experimental group bloodshot eyes, edematous condition are compared with control group 1 and control
Model eye in group 2 mitigates, and the size of animal that conjunctival secretion occurs in experimental group lagophthalmos is less, and degree mitigates.
2nd, corneal fluorescein dyeing scoring
Compared with before drop atropine modeling, control group 1 and control group 2 drip each observing time point relatively drop medicine anterior angle after medicine
Film fluorescent staining scoring conspicuousness increases (P ＜ 0.01)；Each time point relatively drips no difference of science of statistics before medicine after experimental group drop medicine
(P ＞ 0.05).Experimental group is compared with control group 1 and control group 2, before medicine is dripped and after drop medicine in addition to 14d, remaining observing time
Point experimental group is shown in Table 6 significantly lower than control group 1 and control group 2 (P ＜ 0.01).
Cornea fluorescent staining scores (n=10) before and after 6 experimental group of table and control group modeling and after drop medicine
Note：Compared with before this group of modeling, * P ＜ 0.05, * * P ＜ 0.01；Compared with control group 1 is with time point, △ △ P ＜
0.01。
Experimental result shows that eye drops described in embodiment has a constant current modulation for the rabbit dry eyes for preventing Topical atropine
Effect, the rabbit dry eyes performance that atropine ocular fluid can be inhibited to induce, promotes the secretion of rabbit tear, secretory volume dramatically increases, is expected to become
A kind of novel ophthalmically acceptable formulation application is in clinic.
Embodiment 16
The effect of in order to investigate the Moringa flavones of different content, tests embodiment 1, embodiment 10~13, test
Method and result it is as follows：
The qualified BALB/c mouse 150 of quarantine observation is chosen, randomly selects 20 animals as blank control group, remaining
Animal carries out modeling, and antigen preparation is carried out before modeling, that is, takes mouse of the same race, is killed with dislocation method, the disinfection of conventional method eye circumference,
Conjunctiva is completely taken out on superclean bench, is cleaned with physiological saline, is put in the physiological saline of the gentamicin containing 80,000/500ml,
Conjunctival scissors is fragmentated, homogenate is ground into homogenizer.Keep 4 DEG C, on ultrasonication machine crush 1h be put in again centrifuge from
The heart (3000r/min, × 15min).Supernatant is taken out, Coomassie Brilliant Blue measures protein content.Then 0.14M PBS are used again
Protein concentration is diluted to 90 μ g/ml.Isometric conjunctiva antigenic solution is added in complete Freund's adjuvant (CFA), it is fully mixed
It is even into Water-In-Oil solution.Water-In-Oil solution is distinguished into multi-point injection in mouse dorsal sc, cervical lymph node, four limbs axillary lymph
Knot and foot pad, total amount 0.5ml.The mouse that modeling is completed chooses 120, is divided into 6 groups, every group of 20 animal (40 eyeballs),
Half male and half female.Five groups of administration groups are dripped respectively with embodiment 1, embodiment 10, embodiment 11, embodiment 12, embodiment 13, are respectively given
Medicine group dosage setting is 40 g//days of μ (10 μ l//time, 4 times/day), is administered with micro sample adding appliance, is administered 2 weeks.Blank
Control group, model control group give the physiological saline (10 μ l) of isometric(al) every time.The the 1st, 4,7 day after administration, using phenol red cotton thread
Wet length, for 24 hours breakup time of tear film, the indexs such as amount of drinking water, detect each administration group for mouse Keratoconjunctivitis Sicca
Control effect, test result are shown in Table 7~10.
1st, to the influence of the phenol red cotton thread wetted length of mouse Sjogren syndrome model and breakup time of tear film
Result of the test can be seen that administration the 1st day：Compared with blank group, the phenol red cotton thread of model group and each administration group is long
Degree and breakup time of tear film are obviously shortened (P<0.01), compared with model group, the phenol red cotton thread length and tear film of each administration group
Rupture time is without significant difference (P>0.05).It is administered the 4th day：Compared with blank group, the phenol red cotton of model group and each administration group
Line length and breakup time of tear film are obviously shortened, tool statistical significance (P<0.01), compared with model group, each administration group
Phenol red cotton thread length is obviously prolonged (P<0.01), and breakup time of tear film is without significant difference (P>0.05).It is administered the 7th day：With
Blank group compares, and the phenol red cotton thread length and breakup time of tear film of model group and each administration group are obviously shortened (P<0.01), with
Model group compares, and embodiment 1,12,13 groups of phenol red cotton thread length and breakup time of tear film significantly extend (P<0.01) it is, real
The phenol red cotton thread length for applying 10,11 groups of example significantly extends (P<0.01), breakup time of tear film extends (P<0.05).
Table 7 is to the phenol red cotton thread length of mouse Keratoconjunctivitis Sicca and the influence (first day) of breakup time of tear film
Note：With blank group ratio, # represents P<0.05, ## represents P<0.01；Compared with model group, * represents P<0.05, * * tables
Show P<0.01.
Table 8 is to the phenol red cotton thread length of mouse Keratoconjunctivitis Sicca and the influence (the 4th day) of breakup time of tear film
Note：With blank group ratio, # represents P<0.05, ## represents P<0.01；Compared with model group, * represents P<0.05, * * tables
Show P<0.01.
Table 9 is to the phenol red cotton thread length of mouse Keratoconjunctivitis Sicca and the influence (the 7th day) of breakup time of tear film
Note：With blank group ratio, # represents P<0.05, ## represents P<0.01；Compared with model group, * represents P<0.05, * * tables
Show P<0.01.
2nd, to the influence of mouse Sjogren syndrome model amount of drinking water for 24 hours
Result of the test shows：It is administered the 1st, 4,7 day, compared with blank group, the amount of drinking water for 24 hours of model group and each administration group
It has no and significantly reduces (P>0.05), compared with model group, the amount of drinking water for 24 hours of each administration group is without significant difference (P>0.05).
Table 10 to the amount of drinking water for 24 hours of mouse Keratoconjunctivitis Sicca influence (N=20)
Note：With blank group ratio, # represents P<0.05, ## represents P<0.01；Compared with model group, * represents P<0.05, * * tables
Show P<0.01.
What is measured on phenol red cotton thread test theory is eye basis lacrimal secretion, and wetted length and lacrimal secretion are just
Correlation has many advantages, such as that the time is short, irritation is small.Tear film is the important component of ocular immune defense system, and tear film is not
Stablize the integrality that will make destruction tear film barrier, bacteriotoxin and antigenicity substance are easy to directly contact with corneal epithelium, so as to
Lead to the immunopathogenesis reaction of cornea, breakup time of tear film is too short to cause the drying of cornea tissue, and influences the transparent of cornea
Property.Above-mentioned testing experiment chooses phenol red cotton thread, breakup time of tear film and amount of drinking water as Testing index, is as a result shown for 24 hours：
Drop Moringa flavones can be effectively improved mouse Keratoconjunctivitis Sicca, and the phenol red cotton thread wetted length of embodiment each group is significantly high
In other test groups, result is with consistency with breakup time of tear film, with Moringa Huang between embodiment 1,10,11,12,13 groups
The increase of the amount of ketone, to the improvement of mouse Keratoconjunctivitis Sicca without significant difference, therefore the additive amount of Moringa flavones is 0.1
~2g/100mL.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than to the present invention
The limitation of protection domain, although being explained in detail with reference to preferred embodiment to the present invention, those of ordinary skill in the art should
Work as understanding, technical scheme of the present invention can be modified or replaced equivalently, without departing from the reality of technical solution of the present invention
Matter and range.
Claims (10)
1. a kind of medical composite for eye, which is characterized in that include Moringa flavones.
2. medical composite for eye as described in claim 1, which is characterized in that also soft comprising sodium hyaluronate, vitamin E and sulfuric acid
Ossein；The Moringa flavones, sodium hyaluronate, vitamin E and chondroitin sulfate weight ratio be：Moringa flavones：Sodium hyaluronate：
Vitamin E：Chondroitin sulfate=1：(0.15~1)：(0.2~10)：(0.02~0.2).
3. medical composite for eye as claimed in claim 2, which is characterized in that the Moringa flavones, sodium hyaluronate, vitamin E
Weight ratio with chondroitin sulfate is：Moringa flavones：Sodium hyaluronate：Vitamin E：Chondroitin sulfate=1：(0.3~0.5)：
(1~5)：(0.05~0.1).
4. medical composite for eye as described in claim 1, which is characterized in that the dosage form of the medical composite for eye is eye drip
Liquid, gel for eye use or spongarion.
5. medical composite for eye as claimed in claim 4, which is characterized in that in the eye drops, gel for eye use or spongarion
In, the Moringa flavones content is 0.1~2g/100mL.
6. medical composite for eye as described in claim 1, which is characterized in that also comprising pharmaceutic adjuvant, the pharmaceutic adjuvant packet
In bacteriostatic agent, osmotic pressure regulator, pH adjusting agent, thickener, cosolvent, Chinese herbs material, atoleine and yellow petroleum jelly
At least one.
7. medical composite for eye as claimed in claim 5, which is characterized in that the dosage form of the medical composite for eye is eye drip
Liquid, contain per 100mL in the eye drops 1g Moringas flavones, 0.25g sodium hyaluronates, 5g vitamin Es, 0.2g chondroitin sulfates,
0.02g bacteriostatic agents, 0.2g osmotic pressure regulators, 0.1g thickeners, 0.5g pH adjusting agents, 0.1g cosolvents and surplus water.
8. medical composite for eye as claimed in claim 5, which is characterized in that the dosage form of the medical composite for eye is ophthalmically acceptable
Gel contains 1g Moringas flavones, 0.5g sodium hyaluronates, 5g vitamin Es, 0.1g chondroitin sulfates in the gel for eye use per 100mL
Element, 0.02g bacteriostatic agents, 0.2g osmotic pressure regulators, 0.05g thickeners, 0.5g pH adjusting agents, 0.1g cosolvents and surplus
Water.
9. medical composite for eye as claimed in claim 5, which is characterized in that the dosage form of the medical composite for eye is medicament for the eyes
Cream, the spongarion include the component of following parts by weight：1 part of Moringa flavones, 0.3~0.5 part of sodium hyaluronate, vitamin E 1~5
Part, 0.05~0.1 part of chondroitin sulfate, 8~15 parts of wool grease, 2~10 parts of liquid paraffin and 75~96 parts of yellow petroleum jelly.
10. the purposes of any one of claim 1~9 medical composite for eye in medicine preparation, which is characterized in that institute
State drug for improve xerophthalmia, ectodermosis pluriorificialis or alleviate eyes are dry and astringent, visual fatigue or after improving operation, drug
Property, the conjunctival epithelium damage caused by wound, contact lens wear.
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| CN201711364951.7A CN108125996A (en) | 2017-12-18 | 2017-12-18 | It is a kind of for visual fatigue, dry eyes eye-drops preparations |
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|---|---|---|---|
| CN201711364951.7A CN108125996A (en) | 2017-12-18 | 2017-12-18 | It is a kind of for visual fatigue, dry eyes eye-drops preparations |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111991415A (en) * | 2020-09-11 | 2020-11-27 | 华熙生物科技股份有限公司 | Eye care composition and preparation method and application thereof |
| CN112870216A (en) * | 2021-01-29 | 2021-06-01 | 张宽才 | Pharmaceutical composition, preparation and application |
| CN113876863A (en) * | 2021-10-28 | 2022-01-04 | 庞笠民 | Efficacy composition in pure plant eye protection solution and preparation method thereof |
| CN114869885A (en) * | 2022-05-27 | 2022-08-09 | 战璐 | Preparation of honokiol ophthalmic medicine and application of honokiol ophthalmic medicine in fungal keratitis treatment |
-
2017
- 2017-12-18 CN CN201711364951.7A patent/CN108125996A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111991415A (en) * | 2020-09-11 | 2020-11-27 | 华熙生物科技股份有限公司 | Eye care composition and preparation method and application thereof |
| CN111991415B (en) * | 2020-09-11 | 2022-03-01 | 华熙生物科技股份有限公司 | Eye care composition and preparation method and application thereof |
| CN112870216A (en) * | 2021-01-29 | 2021-06-01 | 张宽才 | Pharmaceutical composition, preparation and application |
| CN113876863A (en) * | 2021-10-28 | 2022-01-04 | 庞笠民 | Efficacy composition in pure plant eye protection solution and preparation method thereof |
| CN114869885A (en) * | 2022-05-27 | 2022-08-09 | 战璐 | Preparation of honokiol ophthalmic medicine and application of honokiol ophthalmic medicine in fungal keratitis treatment |
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