CN110075148A - Arasaponin extract is preparing the application in eye medicinal preparation - Google Patents

Abstract

The invention discloses application of the arasaponin extract in preparation prevention and treatment xerophthalmia, eye wound, ocular angiogenesis disease or ocular nerve disease medicament, the xerophthalmia, eye wound, ocular angiogenesis disease or ocular nerve disease, including but not limited to xerophthalmia, retina degenerative disorders, retinal vein obstruction, periphlebitis of retina, hyphema, vitreous hemorrhage, corneal injury, retinal bruise, atrophia nervi optici glaucomatosa, glass-film wart, age-related macular degeneration and diabetic retinopathy.The mode useful agents amount for the topical ocular administration that the present invention uses is few, it is highly-safe, adverse reaction is few, the many advantages such as good patient compliance, avoid drug administration by injection bring security risk, and after changing administration route, metabolic pathway, mechanism of action etc. are different from injection, have preferable potential applicability in clinical practice.

Description

Arasaponin extract is preparing the application in eye medicinal preparation

Technical field

The invention belongs to natural drug technologies, are preparing eye medicinal preparation more particularly to a kind of arasaponin extract In application.

Background technique

Generally existing with eye improper point at present, xerophthalmia disease incidence increases；With the improvement of living standards, retina is quiet Arteries and veins obstruction, diabetic retinopathy, chorioretinopathy, age-related maculopathy, glaucomatous optic The blinding diseases such as atrophy also seriously annoying the daily life of the middle-aged and the old；Though the eye traumas such as hyphema and vitreous hemorrhage Right disease incidence is not high, but its bring feeling of pain and acute reaction also drastically influence the quality of life of patient.

Modern study proves that ginsenoside and notoginsenoside constituents, can significantly reduce surface activity of blood platelet, inhibit blood Platelet sticks and assembles, reaches antithrombus formation, improves the effects of microcirculation；Blood-serum IL-8 after reduction ischemia-reperfusion can be passed through Generation and release, block neutrophil activation, infiltration and aggregation, mitigate the inflammatory reaction of ischemic tissue, to Ischemia Reperfusion Note damage has protective effect；GluR2 positive expression can be enhanced, inhibit transcription and the caspase-3 albumen of caspase-3 mRNA Cracking activation, promote the transcription and the expression of Bcl-2 albumen of bcl-2mRNA, reduce Apoptosis, promote the survival of neuron And injury repair；It can be obviously shortened bleeding and clotting time, there is good hemostasia effect；Experimental artery congee can be significantly inhibited The aortic tunica intima patch of sample hardening rabbit is formed；The increase of capillary permeability caused by acute inflammation, inflammatory can be oozed out, Tissue edema, leukoplania and later period granulation tissue hyperplasia have apparent inhibiting effect, and can inhibit UV induce at Fibrocyte MMP-1 hypersecretion promotes the expression of vascular endothelial growth factor and Basic Fibroblast Growth Factor, promotes wound group The healing knitted.

A variety of pharmacological activity of the type natural products have been used for the treatment of all kinds of cardiovascular and cerebrovascular diseases, extract quilt Drugs listings such as " " Xuesaitong Injection "s ", " perhexiline " and " thrombus is logical " is made.However it is never a for eye wound, eye blood The safe and effective product of the eye problems such as pipe disease and ocular nerve disease asks city.Thrombus is logical, Xuesaitong injection also exists Clinic is widely used in treating retinal vein embolism, such injection dosage is big, and the course for the treatment of is long (one month), is administered to There are higher security risks for medicine；And national drug adverse reaction inspection center can all receive a large amount of related adverse reaction every year Report, including systemic damage: fever, shiver with cold, anaphylactoid reaction, anaphylactic shock etc.；Respiratory system damage: uncomfortable in chest, breathing It is difficult, be short of breath, asthma, the edema of the larynx etc.；Skin and its pruritus: fash, itch, the property deprived dermatitis etc.；Heart rate and the heart Restrain disorder: palpitaition, tachycardia etc.；Maincenter and peripheral neverous system damage: dizziness has a headache, twitches, trembling；Gastronintestinal system Damage: Nausea and vomiting etc.；Cardiovascular damage: cyanosis, flush, blood pressure decline, blood pressure raising etc.；Other damages include blood Urine, dysfunction of liver etc..Chinese patent CN102688479B discloses a kind of based on polyglutamic acid and Porcine HGF Want the eye patch energy prevention dry eyes of effective component；Chinese patent CN102512433B discloses a kind of luteolin grape alditol Sour glycosides is used to treat the purposes of retinal vein obstruction；Chinese patent discloses the type natural products for visual fatigue Patent, i.e. patent CN107898816A disclose " eye medicinal preparation and its application ", its composition notoginsenoside R, Radix Notoginseng Saponin(e R2, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rd, Ginsenoside Rf, Ginsenoside Rc, ginsenoside Rh 1 and seven leaf gallbladder glycosides Ⅸ etc., have preferable effect for alleviating visual fatigue；In State patent CN102813666A " application of the notoginsenoside R in the drug of prevention and treatment neuro-ophthalmic disease " points out to infuse by vein The administration mode penetrated, monomeric compound notoginsenoside R have preferable therapeutic effect to many ocular nerve diseases.Currently, It has no using such composition of natural products through topical ocular administration for preventing and treating eye wound, ocular angiogenesis disease and eye The pharmaceutical preparation and its novel form of portion's neurogenic disease etc..

Summary of the invention

Goal of the invention: it is directed to the above-mentioned prior art, this application provides a kind of arasaponin extracts to prepare ophthalmically acceptable medicine Application in object preparation.

Technical solution: arasaponin extract of the present invention prevents and treats xerophthalmia, eye wound, ocular angiogenesis in preparation Application in property disease or ocular nerve disease medicament.

Wherein, the xerophthalmia, eye wound, ocular angiogenesis disease or ocular nerve disease, including but not limited to Xerophthalmia, retina degenerative disorders, retinal vein obstruction, periphlebitis of retina, hyphema, vitreous hemorrhage, Corneal injury, retinal bruise, atrophia nervi optici glaucomatosa, glass-film wart, age-related macular degeneration and diabetes view Retinopathy.

The xerophthalmia especially those evaporated strong type xerophthalmia (tear deficient dry eye), but the present invention is to all The dry and astringent symptom of disease bring ocular has relaxation effect.Wherein, especially those a variety of causes cause the eye wound Hyphema and vitreous hemorrhage, also including but not limited to contusion of cornea, scleral contusion, commotio retinae and contusion, train of thought Film rupture, Eye chemical damage, ocular thermal burning and radiativity eye injury.Wherein, the ocular angiogenesis disease especially those Retinal vein obstruction and diabetic retinopathy, also including but not limited to around retinal arterial obstruction and retinal vein Scorching (retinal vasculitis).Wherein, the ocular nerve disease especially those atrophia nervi optici glaucomatosas also include But it is not limited to retina regression denaturation, a variety of chorioretinopathies (central serous chorioretinopathy) and year Age is macular degeneration related.

Further, the arasaponin extract improves eye microcirculation, inhibits eye by inhibiting eye thrombosis Portion's nerve cell apoptosis, hemostasis and promotion eye wounds organization healing.

The dosage form of herein described drug includes ophthalmic solution, gel for eye use, ophthalmic ointment, eye lotions or intraocular injection Agent.The compound of the present invention can be topically applied to eye, for example, under part, conjunctiva, after eyeball, under eye circumference, retina, choroid Upper or intraocular application.It include the aqueous solution for being configured to eye drops for being directly applied to the particularly useful pharmaceutical composition of eyes And/or suspension and it is configured to the thickening solution and/or suspension of gel for eye use (including gel-forming solution) or ointment, it is Ophthalmic solution, ophthalmic ointment, eye lotions, intraocular injection agent and gel for eye use etc..Other dosage forms for ophthalmic drug delivery Including ophthalmically acceptable insert (ocular insert), intravitreal injection agent and implantation material.Injectable solution can be used fine needle direct In injection cornea, crystalline lens and vitreum or its adjacent tissue.

Combine other medicative eye-drops preparations of tool disclosed herein as well is the arasaponin extract preparing Prevent and treat the application in xerophthalmia, eye wound, ocular angiogenesis disease or ocular nerve disease medicament.

Other eye-drops preparations include but is not limited to anti-infective ingredient, anti-inflammatory drug, antiallergic (including antihistamine), artificial Tear vasoconstrictor, vasodilator, local anesthetic, antalgesic, ocular hypotensive agent, immunomodulator, antioxidant, dimension Raw element and minerals, enzyme inhibitor and peptase, cell factor inhibitors etc..

Further, the eye treatment agent being used in combination is selected from Acular (Acular) (ketorolac tromethamine Ophthalmic solution) 0.5%, Acuvail (ketorolac tromethamine), AK-Con-A (naphazoline medicament for the eyes), Akten (hydrochloric acid benefit Cacaine), Alamast, Alphagan (Brimonidine), Alrex, Astepro (azelastine Hcl nasal spray), AzaSite (Ah Miramycin), Bepreve (bepotastine besilate ophthalmic solution), Besivance (the ophthalmically acceptable suspension of besifloxacin), The sterile irrigating solution of Betaxon, BSS, Cosopt, Durezol (Difluprednate), Eylea (VEGF Trap), Lotemax, Lucentis (Lucentis), Lumigan (bimatoprost ophthalmic solution), Macugen (piperazine Jia Tani), Ocuflox (oxygen fluorine Husky star ophthalmic solution) 0.3%, OcuHist, Ozurdex (dexamethasone), Quixin (lavo-ofloxacin), Rescula (Uno Forefront ketone isopropyl ophthalmic solution) 0.15%, Restasis (the ophthalmically acceptable lotion of cyclosporin), Salagen tablet, Travatan (west is more by (travoprost ophthalmic solution), Valcyte (valganciclovir hydrochloride), trifluorothymidine (Viroptic), Vistide Fu Wei), Visudyne (injection Verteporfin), Vitrasert implantation material, Fomivirsen injection, ZADITOR, Zioptan (tafluprost ophthalmic solution), Zirgan (ganciclovir ophthalmic gel), Zymaxid (the ophthalmically acceptable solution of gatifloxacin), atropic Product, Flurbiprofen, eserine (Physostimine), Pai Liming (Azopt), gentamicin, pilocarpine (Proparacaine), bacitracin, Goniosol (Goniosol), polymyxin B, povidone iodine (Betadine), gramicidins, prednisolone, betaxolol, Humorsol, proparacaine, Betoptic (Betoptic), Hylartin, Propine, brinzolamide, hypertonic NaCl, Puralube, BSS, indocyanine green (Indocycanine Green), rose-red (Rose Bengal), carbachol, Itraconazole, Sodium Hyaluronate, cephalo azoles Quinoline, Latanoprost, suprofen, Celluvisc (Celluvisc), mannitol, terramycin, chloramphenicol, methazolamide, thiophene Lip river That, Ciloxan, Miconazole, tobramycin, Ciprofloxacin, Miostat, triamcinolone, Cosopt, Muro 128, trifluoro urine Glycosides, Demecarium, neomycin, Tropicamide, dexamethasone, methazolamide (Neptazane), Trusopt, Dipivefrine, Ocuflox, arabinosy ladenosine, Dorzolamide, Ofloxacin, Vira-A, adrenaline, oxytetracycline, trifluorothymidine, fluorescein, benzene Adrenaline and Xalatan (Xalatan).

Wherein, inhibit, prevention or reversing function obstacle do not need 100% inhibition, prevention, elimination or reverse.The type " effective quantity " of the medical composite for eye of natural products is the amount for inhibiting, preventing or reversing individual a variety of ophthalmology diseases. Medical composite for eye of the invention is applied to subject in need to treat the effective quantity of dysopia.As used herein , " therapeutically effective amount " means to mitigate sign, symptom or the cause of disease of individual a variety of ophthalmology diseases or life needed for any other The dosage of at least one of object system change.In prophylactic use, term " prevention effective dose ", which means to be applied to, is susceptible to suffer from spy The dosage for determining disease or the patient under specified disease risk can be the dosage identical or different with therapeutically effective amount. The effective quantity of composition for particular individual may depend on individual, the severity of individual state, application preparation type, Administration frequency and duration for the treatment of.According to the present invention, though eye medicinal preparation of the invention in liquid drops with opposite Lower concentration, such as 10^-9M to 10³In M any concentration application, can also by daily only once, twice, it is three times or more Secondary application so rapidly carries out to reverse such dysopia.

Further, the arasaponin extract is selected from notoginsenoside R, Ginsenoside Ng-R2, ginsenoside Rg1, ginseng Saponin(e Rg2, ginsenoside Re, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rd, ginsenoside Rf, Ginsenoside Rc, One of ginsenoside Rh 1 and seven leaf gallbladder glycosides Ⅸ are a variety of.

Preferably, the following component for being 60~90% containing content summation in the arasaponin extract: notoginsenoside R1, Ginsenoside Ng-R2, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, ginsenoside Rb1, ginsenoside Rb2, ginseng Saponin(e Rd, ginsenoside Rf, Ginsenoside Rc, ginsenoside Rh 1 and seven leaf gallbladder glycosides Ⅸ.

It is further preferred that notoginsenoside R content is 3.0% or more, ginsenoside in the arasaponin extract Rg1 content is 20.0% or more, ginsenoside Re's content is 1.5% or more, ginsenoside Rb1's content is 25.0% or more, people Joining saponin(e Rd content is 2.5% or more.

The crude drug source of the arasaponin extract includes but is not limited to Radix Notoginseng, people's participation American Ginseng etc..Wherein Radix Notoginseng Dry root, rhizome, stem, flower selected from Chinese medicine panax araliaceae plant Panax notoginseng (Burk.) F.H Chen and Fruit.

The drug can be using arasaponin extract as sole active ingredient.Wherein, the matter of arasaponin extract Measuring percentage composition is 0.02~30.0%, preferably 0.1%-10.0%, remaining is 60.0~99.9% to be pharmaceutically acceptable Carrier and/or auxiliary material.

The pharmaceutically acceptable carrier is water, buffer or sodium chloride solution.In some embodiments, the pharmacy Upper acceptable carrier is sterile.In other embodiments, which is ointment.In other implementations In scheme, which is gel.Gel can be used gel preparing materials well known in the art and be matched System.

Heretofore described arasaponin extract can also be substituted for its corresponding pharmaceutically acceptable free acid, trip From alkali, salt (for example, acid or base addition salts), hydrate or prodrug etc..It " pharmaceutically acceptable salt " or " can pharmaceutically connect The acid received " refers respectively to the pharmaceutically acceptable organic or inorganic salt of the type natural products or acid.Gegenion can be stabilization Any organic or inorganic part of charge on parent compound.In addition, pharmaceutically acceptable salt (or acid) can be in its structure In have more than one charge atom.Multiple charge atoms are that the example of a part of pharmaceutically acceptable salt (or acid) can have There are multiple gegenions.Therefore, pharmaceutically acceptable salt (acid) can have one or more charge atoms and/or one or more A gegenion.

Pharmaceutical composition can also be prepared by the way that the present composition to be dissolved in solvent appropriate.Solvent appropriate Including but not limited to water, salting liquid (for example, NaCl), buffer solution, ointment, gel or other solvents.In preparing eye drops The aqueous solution and diluent for suspension used may include distilled water, physiological saline etc..These pharmaceutical compositions can pass through Following manner prepare: according to conventional methods by compound optionally with medicated premix appropriate such as excipient, disintegrating agent, bonding Agent, lubricant, diluent, buffer, preservative, wetting agent, emulsifier, dispersing agent, stabilizer and dissolution aids are mixed together, Dilution or dissolution, and prepared in a usual manner according to dosage form.Multiple additives can be comprised in eye drops, ophthalmically acceptable solidifying as needed In glue and/or ophthalmic ointment.These additives may include being adapted for contact with eye or enclosing in eye circumference to be used without excessive toxicity, non-phase Supplementary element, additive or the carrier of capacitive, unstability, irritation, allergy etc..It can be in the appropriate case into preparation Be added additive for example solvent, matrix, cosolvent, suspending agent, thickener, emulsifier, stabilizer, buffer, isotonicity regulator, PH adjusting agent, chelating agent, agent of releiving, preservative, corrigent, flavoring agent, colorant, excipient, adhesive, lubricant, surface Activating agent, sorbefacient, dispersing agent, preservative, solubilizer etc..

For example, can be by the way that compound be dissolved in the sterile water dissolved with surfactant and optionally adds medicine appropriate Object additive such as preservative, stabilizer, buffer, antioxidant and viscosity-improving agents prepare eye drops.For example, addition buffering Agent is to keep pH constant, and the buffer may include pharmaceutically acceptable buffer, such as borate buffer solution, citrate Buffer, tartrate buffer, phosphate buffer etc..Other than buffer, it can also be added into eye drops isotonic Agent is to prepare the preparation isotonic with tear.Isotonic agent includes but is not limited to carbohydrate, polyalcohol and salt.So that the infiltration of eye drops The amount that pressure is equal to tear osmotic pressure thoroughly adds isotonic agent.Preservative can be added to maintain the complete of eye drops and/or ophthalmic ointment Whole property.In some embodiments, increase eye-drops preparations such as eye drops, gel for eye use and/or ophthalmic ointment using thickener Viscosity.Eye drops, gel for eye use and/or ophthalmic ointment can be prepared by sterile working, or alternatively in preparation Suitable stage sterilizes.For example, sterile pharmaceutical composition can be prepared by sterilely mixing sterile ingredients.Alternatively, should Sterile pharmaceutical composition then can be prepared final preparation sterilizing by first mixing ingredient.Sterilizing methods may include but unlimited In heat sterilization, radiation and filtering.Ophthalmic ointment (eye ointment) can by mixing active constituent into the matrix for being used to prepare eye ointment, Pharmaceutical preparation is then configured to come sterile preparation using any method known in the art.

Certain embodiments of the present invention are further related to comprising can be used for treating and/or preventing relevant to a variety of ophthalmology diseases The kit of the component of symptom.Such kit includes containing the natural products of the present invention in pharmaceutically acceptable carrier The container of composition, and make and xerophthalmia, eye wound, ocular angiogenesis about composition of natural products of the present invention is applied The explanation that disease at least one symptom relevant to ocular nerve disease etc. is improved or prevented.Included in present document relates to Container in some kits is the dropper for applying eye drops.In other embodiments, which is soft for distributing The pipe of cream or gel.In other embodiments, which is any suitable container for drug delivery, including but unlimited In syringe or suitable for the ocular delivery of drug or other containers of local application.Unless otherwise defined, used herein all Meaning identical with the meaning that those skilled in the art are generally understood that technical and scientific term all has. Although similar or equivalent any method, apparatus and material implementation for use in the present invention or test with those described herein, But what be will now be described is preferred method, apparatus and material.

The utility model has the advantages that invention applies antithrombus formation, improvement microcirculation, promotion minds that the type natural products has Survival and injury repair, hemostasis and promotion healing up of traumatic tissues isoreactivity through member, are made specifically for eye part disease medication Dosage form, pharmacological evaluation prove the drug to xerophthalmia, eye wound, ocular angiogenesis disease and ocular nerve disease etc. to eye Damage caused by eyeball and eyesight has healing effect.Meanwhile the mode useful agents amount of topical ocular administration that the present invention uses is few, Highly-safe, adverse reaction is few, and many advantages such as good patient compliance avoid drug administration by injection bring security risk, and change After becoming administration route, metabolic pathway, mechanism of action etc. are different from injection, have preferable potential applicability in clinical practice.

Detailed description of the invention

Fig. 1 is the optical microphotograph of embodiment 12 as a result, wherein Fig. 1 a is retina test result, and Fig. 1 b is choroid examination Test result；

Fig. 2 is the statistical graphical representation that the application drug alleviates eye sensation of dryness.

Specific embodiment

The application is explained in detail combined with specific embodiments below.

Embodiment one

The type native compound multi-dose eye drops (one)

10 grams of the type native compound are taken, 300 milliliters of physiological saline, 0.22 μm of film refined filtration are dissolved in, dilution is settled to 1000 milliliters, sealing, high-temperature sterilization dispenses to eye drop bottle, 10 milliliters every bottle, obtains 100 eye drops.

Embodiment two

The type native compound multi-dose eye drops (two)

5 grams of the type native compound are taken, 300 milliliters of physiological saline, 0.22 μm of film refined filtration are dissolved in, dilution is settled to 1000 Milliliter, sealing, high-temperature sterilization dispense to eye drop bottle, 10 milliliters every bottle, obtain 100 eye drops.

Embodiment three

The type native compound single dose eye drops (one)

10 grams of the type native compound are taken, 300 milliliters of physiological saline, 0.22 μm of film refined filtration are dissolved in, dilution is settled to 1000 milliliters, sealing, high-temperature sterilization dispenses to eye drop bottle, 0.4 milliliter every bottle, obtains 25000 eye drops.

Example IV

The type native compound single dose eye drops (two)

5 grams of the type native compound are taken, 300 milliliters of physiological saline, 0.22 μm of film refined filtration are dissolved in, dilution is settled to 1000 Milliliter, sealing, high-temperature sterilization dispense to eye drop bottle, 0.4 milliliter every bottle, obtain 25000 eye drops.

Embodiment five

The type native compound intraocular injection agent (one)

4 grams of the type native compound are taken, 300 milliliters of physiological saline, 0.22 μm of film refined filtration are dissolved in, dilution is settled to 1000 Milliliter, packing to ampoule bottle, 2 milliliters every bottle, sealing, high-temperature sterilization obtains 500 intraocular injection agent.

Embodiment six

The type native compound intraocular injection agent (two)

8 grams of the type native compound are taken, 300 milliliters of physiological saline, 0.22 μm of film refined filtration are dissolved in, dilution is settled to 1000 Milliliter, packing to ampoule bottle, 2 milliliters every bottle, sealing, high-temperature sterilization obtains 500 intraocular injection agent.

Embodiment seven

The type native compound intraocular injection agent (freeze-drying)

It takes the type native compound to be configured to lyophilized stoste, removes pyrogen removal, dispensed after micro-filtration, sterilized, in -80 DEG C of refrigerators Pre-freeze 6h is freeze-dried 12h to get the type native compound intraocular injection agent freeze-dried powder.

Embodiment eight

The intraocular eye ointemnt of the type native compound

Medical yellow petroleum jelly, glycerol, lanolin are taken, is uniformly mixed in 8:2:1 ratio, spongarion matrix is made.Take 3000 Gram matrix is added 30 grams of the type native compound, mixes, obtains the type native compound spongarion, aseptic subpackaged, and every 3 grams, obtain 1000.

Embodiment nine

The type native compound external application eye cream

It takes PLURONICS F87 to emulsify, glycerol is added, spongarion matrix is uniformly made in mixed with propylene glycol.3000 grams of matrix are taken, 30 grams of the type native compound are added, mixes, obtains the type native compound spongarion, it is aseptic subpackaged, it 3 grams every, obtains 1000.

Embodiment ten

The type native compound eye lotions

According to Chinese Pharmacopoeia the 4th lotion regulation, 20 grams of the type native compound are taken, adds what water for injection configured etc. Osmometer solution is stirred evenly to 1000 milliliters, is sub-packed in 100 mL of saline bottles, is jumped a queue, aluminium lid sealing, 100 DEG C of flowing steam disinfections 30min.

Embodiment 11

Osmometry

The product into embodiment seven of above-described embodiment one is taken respectively, according to " Chinese Pharmacopoeia " the 4th 0632 regulation, is measured Osmotic pressure is between 296.000-308.000mOsm/l.

Embodiment 12

Treat the experiment of retinal vein embolism

(1) experimental animal and grouping:, being divided into 3 groups by new zealand rabbit 7, normally 2 rabbits (number A, B) of group, and totally four Eyeball, remaining 5 rabbits (number C, D, E, F, G), it is model group that left eye, which gives physiological saline, and right eye is given the type and naturally changed Conjunction object eye drops is administration group.

(2) experimental material: 1% atropine, 2% procaine, the type native compound eye drops, physiological saline.

(3) inspection internal organs: rabbit fundus tissue.

(4) inspection method: the 10% chloraldurate general anesthesia of intravenous rabbit or intraperitoneal injection, instil after anesthesia, in eyelid 1% Ah 5 μ L of tropine expands pupil, and 2% procaine, 5 μ L is added dropwise after 15min and carries out corneal anesthesia.The red 20mgkg-1 of intravenous injection tiger, volume Mirror is set after 1m Lkg, 1min before surgery and in vitro position indicator mediates the lower cold laser that carries out to irradiate retinal vein, preparation view Nethike embrane venous embolism model.Normal group is not processed.Administration group is 1.25% the type native compound eye drops using concentration (physiological saline solution) eye drip one week, once a day, 35 μ l, model group give physiological saline in parallel every time.It is cutd open after experiment Take eyeball, draw materials after fixed, be dehydrated, paraffin embedding, film-making (4 μ m-thick), HE dyeing, observe under an optical microscope retina with Each position of choroid checks for lesion and lesion type, degree.

(5) inspection result: the result is shown in Figure 1 a, Fig. 1 b, according to diagram as it can be seen that administration group inner nuclear layer oedema disappears, vacuole subtracts Few, karyopycnosis phenomenon mitigates；Thrombi disappears or becomes smaller in choroidal artery.It can be seen that this product is to Experimental retinal Venous embolism has preferable therapeutic effect.

Embodiment 13

Alleviate xerophthalmia experiment one

(1) experimental method: fluorescein sodium labelling method or tear qualitative and quantitative analysis method (lower progress of having ready conditions) preliminary characterization In the ocular drug generation of this product, moves behavior.

(2) experimental animal and grouping:, being divided into 4 groups by new zealand rabbit 4, every rabbit right and left eyes be one group (number A, B, C, D), it is model group that left eye, which gives physiological saline, and it is administration group that right eye, which gives the type native compound eye drops,.

(3) experimental material: the type native compound eye drops, physiological saline.

(4) experimentation:

Fluorescein sodium labelling method

(5) inspection method: every group in identical multiple periods, continuous observation fluorescence coating is strong and weak in the UV lamp.

(6) inspection result:

Residence time	A	B	C	D
					Left eye (physiological saline)	45 seconds	45 seconds	30 seconds	45 seconds
Right eye (eye drops)	4 points 45 seconds	5 points 30 seconds	5 points 30 seconds	4 points 30 seconds

According to above-mentioned statistics as it can be seen that the residence time of the type native compound eye drops ocular is five times of physiological saline More than, bioavilability is higher, dramatically increases tear film stability, and it is dry to alleviate ocular.

Embodiment 14

Alleviate xerophthalmia experiment two

(1) experimental method: experience investigation on probation

(2) experimental material: the type native compound eye drops, ZHENSHIMING DIYANYE

(3) person on probation: male to female ratio is impartial, the age between 18~60 years old, do not use ophthalmic preparations 45 in the recent period Trier is divided into two groups, respectively short beta test group and for a long time group on probation by people, wherein 40 people of short beta test group, it is long-term on probation 5 people of group.

(4) experimentation:

1. short beta test group: trier's long focus electronic product screen uses this product after not feeling good, in interval phase With questionnaire is repeatedly filled in after the period, content includes whether usage comfort, if spinosity excitation, if having to visual fatigue and change It is kind, if to have side effect etc..

2. trying out group for a long time: according to short-term group trier's trial state, long-term group trier is used for a long time in one month This product tracks follow-up to it, understands the validity of this product, guarantees trier's drug safety.

(5) trier's investigation result:

1, after trying out the type native compound eye drops, xerophthalmia remission effect is strong, while use feeling and compliance are good, Statistical result see the table below:

Volunteer's ratio that visual fatigue symptom has alleviation is mentioned in evaluation	91.67%
		Visual fatigue symptom is mentioned in evaluation the volunteer's ratio significantly alleviated	58.33%
It is ready to reuse volunteer's ratio of this product	87.50%

The index symptom of observation: blurred vision sense, eye muscle ache sense, eye sensation of dryness, abnormal secretion, eye burn Burning sense, ocular pruritis, eye have foreign body sensation, shed tears；Project is described with scoring, is divided into 0-5 points, and 0 point is asymptomatic, 1- 2 points are to have light symptoms, and 3-4 points are to have manifest symptom, and 5 points are serious symptoms occur；Volunteer's feedback information is subjected to variance Analysis, P < 0.05 are to have alleviation, and P < 0.01 is significant alleviates.

2, Fig. 2 be to suitable user using the application eye drops alleviate eye sensation of dryness effect count, according to diagram as it can be seen that After trying out the type native compound eye drops for a period of time, it is dry and astringent eye can be obviously improved.

Claims (10)

1. arasaponin extract is in preparation prevention and treatment xerophthalmia, eye wound, ocular angiogenesis disease or ocular nerve disease Application in drug.

2. application according to claim 1, which is characterized in that the xerophthalmia, eye wound, ocular angiogenesis disease or Ocular nerve disease, including but not limited to xerophthalmia, retina degenerative disorders, retinal vein obstruction, retinal vein Surrounding inflammation, hyphema, vitreous hemorrhage, corneal injury, retinal bruise, atrophia nervi optici glaucomatosa, glass-film wart, year Age is macular degeneration related and diabetic retinopathy.

3. application according to claim 1 or 2, which is characterized in that the drug is improved by inhibiting eye thrombosis Eye microcirculation inhibits ocular nerve Apoptosis, hemostasis and promotes eye wounds organization healing, reaches therapeutic purposes.

4. application according to claim 1 or 2, which is characterized in that the dosage form of the drug includes ophthalmic solution, ophthalmically acceptable solidifying Glue, ophthalmic ointment, eye lotions or intraocular injection agent.

5. arasaponin extract combine other have medicative eye-drops preparations preparation prevention and treatment xerophthalmia, eye wound, Application in ocular angiogenesis disease or ocular nerve disease medicament.

6. application according to claim 1 or 2, which is characterized in that the arasaponin extract be selected from notoginsenoside R, Ginsenoside Ng-R2, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, ginsenoside Rb1, ginsenoside Rb2, ginseng soap One of glycosides Rd, ginsenoside Rf, Ginsenoside Rc, ginsenoside Rh 1 and seven leaf gallbladder glycosides Ⅸ are a variety of.

7. application according to claim 6, which is characterized in that containing content summation in the arasaponin extract is 60 ~90% following component: notoginsenoside R, Ginsenoside Ng-R2, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, people Join saponin(e Rb1, ginsenoside Rb2, ginsenoside Rd, ginsenoside Rf, Ginsenoside Rc, ginsenoside Rh 1 and seven leaf gallbladder glycosides Ⅸ。

8. application according to claim 6, which is characterized in that in the arasaponin extract, notoginsenoside R content For 3.0% or more, Determination of Content of Ginsenoside Rg_1 be 20.0% or more, ginsenoside Re's content is 1.5% or more, ginsenoside Rb1 Content is 25.0% or more, ginsenoside Rd's content is 2.5% or more.

9. application according to claim 1 or 2, which is characterized in that the arasaponin extract is in the drug Mass percentage is 0.02~30.0%.

10. application according to claim 1 or 2, which is characterized in that the drug is using arasaponin extract as uniquely Effective component；Wherein, the mass percentage of arasaponin extract be 0.1~40.0%, remaining 60.0~99.9% be medicine Acceptable carrier and/or auxiliary material on.