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

Abstract

The invention discloses the application of Panax notoginseng saponin extract in the preparation of medicines for preventing and treating dry eye, ocular trauma, ocular vascular disease or ocular neurological disease. The dry eye, ocular trauma, ocular vascular disease Disease or neurological disease of the eye, including but not limited to dry eye, retinal degenerative disorders, retinal vein occlusion, periretinal phlebitis, hyphema, vitreous hemorrhage, corneal injury, retinal contusion, glaucomatous optic atrophy, vitreous membrane Warts, age-related macular degeneration, and diabetic retinopathy. The mode of topical ocular administration adopted by the present invention has many advantages such as less dosage, high safety, less adverse reactions, and good patient compliance, and avoids the safety risk brought by injection administration, and after changing the route of administration, Its metabolic pathway and mechanism of action are different from those of injections, and it has a good clinical application prospect.

Description

Application of Notoginsenoside Extract in Preparation of Ophthalmic Pharmaceutical Preparations

technical field

The invention belongs to natural medicine technology, and in particular relates to the application of a notoginseng saponin extract in the preparation of ophthalmic pharmaceutical preparations.

Background technique

At present, improper use of eyes is common, and the incidence of dry eye syndrome is increasing; with the improvement of living standards, retinal vein occlusion, diabetic retinopathy, chorioretinopathy, age-related macular degeneration, glaucomatous optic atrophy and other blinding diseases It also seriously plagues the daily life of middle-aged and elderly people; although the incidence of ocular trauma such as anterior chamber hemorrhage and vitreous hemorrhage is not high, the pain and acute reaction they bring seriously affect the quality of life of patients.

Modern studies have proved that ginsenosides and notoginseng saponins can significantly reduce platelet surface activity, inhibit platelet adhesion and aggregation, achieve anti-thrombosis, improve microcirculation, etc.; can reduce serum IL-8 levels after ischemia-reperfusion. Produce and release, block the activation, infiltration and aggregation of neutrophils, reduce the inflammatory response of ischemic tissue, and have a protective effect on ischemia-reperfusion injury; it can enhance the positive expression of GluR2, inhibit the transcription of caspase-3 mRNA and caspase- The cleavage and activation of 3 proteins can promote the transcription of bcl-2 mRNA and the expression of Bcl-2 protein, reduce cell apoptosis, and promote the survival and damage repair of neurons; it can significantly shorten the bleeding and coagulation time, and has a good hemostatic effect; it can significantly Inhibit the formation of aortic intima plaque in rabbits with experimental atherosclerosis; it can significantly improve the capillary permeability increase, inflammatory exudation, tissue edema, leukocyte migration and late granulation tissue hyperplasia caused by acute inflammation It can inhibit UV-induced high secretion of fibroblast MMP-1, promote the expression of vascular endothelial growth factor and basic fibroblast growth factor, and promote the healing of wound tissue.

The various pharmacological activities of this type of natural product have been used in the treatment of various cardiovascular and cerebrovascular diseases, and its extracts have been made into drugs such as "Xuesaitong", "Guanxinning" and "Xueshuantong". However, there has never been a safe and effective product for ocular problems such as ocular trauma, ocular vascular diseases and ocular neurological diseases. Xueshuantong and Xuesaitong injections are also widely used clinically to treat retinal vein embolism. The dosage of these injections is large, the course of treatment is long (one month), and there is a high safety risk in injection administration; and the national adverse drug reaction detection The center receives a large number of adverse reaction reports every year, including systemic damage: fever, chills, anaphylaxis, anaphylactic shock, etc.; respiratory system damage: chest tightness, dyspnea, shortness of breath, asthma, laryngeal edema, etc.; skin and Damage to its appendages: rash, itching, exfoliative dermatitis, etc.; heart rate and rhythm disorders: palpitations, tachycardia, etc.; damage to the central and peripheral nervous system: dizziness, headache, convulsions, tremors, etc.; damage to the gastrointestinal system: nausea, vomiting, etc. Cardiovascular system damage: cyanosis, flushing, blood pressure drop, blood pressure rise, etc.; other damages include hematuria, abnormal liver function, etc. Chinese patent CN102688479B discloses an eye patch with polyglutamic acid and cell growth factor as the main active ingredients to prevent dry eye; Chinese patent CN102512433B discloses a kind of luteolin glucuronide for the treatment of retinal vein occlusion Chinese patent discloses a patent of this type of natural product for visual fatigue, that is, patent CN107898816A, which publishes "ophthalmic pharmaceutical preparations and their applications", the composition of which is notoginsenoside R1, notoginsenoside R2, and ginsenoside Rg1 , ginsenoside Rg2, ginsenoside Re, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rd, ginsenoside Rf, ginsenoside Rc, ginsenoside Rh1 and aescin Ⅸ, etc., have a good effect on relieving visual fatigue ; Chinese patent CN102813666A "Application of Notoginsenoside R1 in Drugs for the Prevention and Treatment of Neuro-ophthalmological Diseases" pointed out that the monomer compound Notoginsenoside R1 has a good therapeutic effect on many ocular neurological diseases through intravenous injection. . At present, there are no pharmaceutical preparations and new dosage forms using such natural product compositions for the prevention and treatment of ocular trauma, ocular vascular diseases and ocular neurological diseases through topical ocular administration.

SUMMARY OF THE INVENTION

Purpose of the invention: Aiming at the above-mentioned prior art, the application provides the application of a notoginseng saponin extract in the preparation of ophthalmic pharmaceutical preparations.

Technical solution: the application of the notoginseng saponin extract of the present invention in the preparation of drugs for the prevention and treatment of dry eye, ocular trauma, ocular vascular disease or ocular neurological disease.

Wherein, the dry eye, ocular trauma, ocular vascular disease or ocular neurological disease, including but not limited to dry eye, retinal degenerative disease, retinal vein occlusion, retinal periphlebitis, hyphema, Vitreous hemorrhage, corneal injury, retinal contusion, glaucomatous optic atrophy, drusen, age-related macular degeneration, and diabetic retinopathy.

Said dry eye especially refers to those evaporative dry eye (tear deficiency type dry eye), but the present invention has alleviating effects on ocular surface dryness caused by all diseases. Wherein, the eye trauma mentioned especially refers to hyphema and vitreous hemorrhage caused by various reasons, including but not limited to corneal contusion, scleral contusion, retinal concussion and contusion, choroidal rupture, ocular chemical injury, ocular thermal burn and radiation eye damage. Wherein, the ocular vascular diseases especially refer to retinal vein occlusion and diabetic retinopathy, including but not limited to retinal artery occlusion and retinal periphlebitis (retinal vasculitis). Wherein, the neurological diseases of the eye especially refer to glaucomatous optic atrophy, including but not limited to retinal degeneration, various chorioretinopathy (central serous chorioretinopathy) and age-related macular degeneration.

Furthermore, the extract of notoginseng saponins inhibits ocular thrombus formation, improves ocular microcirculation, inhibits ocular nerve cell apoptosis, stops bleeding and promotes healing of ocular wound tissues.

The dosage form of the drug described in this application includes ophthalmic solution, ophthalmic gel, ophthalmic ointment, ophthalmic lotion or intraocular injection. Compounds of the invention may be administered topically to the eye, eg, topically, subconjunctivally, retrobulbarly, periocularly, subretinally, suprachoroidally or intraocularly. Pharmaceutical compositions particularly useful for direct administration to the eye include aqueous solutions and/or suspensions formulated as eye drops and thickened solutions and/or suspensions formulated as ophthalmic gels (including gel-forming solutions) or ointments, It is an ophthalmic solution, an ophthalmic ointment, an eye lotion, an intraocular injection, an ophthalmic gel, and the like. Other dosage forms for ophthalmic drug delivery include ocular inserts, intravitreal injections and implants. Injectable solutions can be injected directly into the cornea, lens, and vitreous, or adjacent tissues, using a fine needle.

The application also discloses the application of the notoginseng saponin extract in combination with other ophthalmic preparations with therapeutic effects in the preparation of drugs for the prevention and treatment of dry eye, ocular trauma, ocular vascular disease or ocular neurological disease.

Other ophthalmic agents include, but are not limited to, anti-infective agents, anti-inflammatory agents, anti-allergic agents (including antihistamines), artificial tears vasoconstrictors, vasodilators, local anesthetics, analgesics, intraocular pressure lowering agents, immunomodulatory agents agents, antioxidants, vitamins and minerals, enzyme inhibitors and peptidases, cytokine inhibitors, etc.

Further, the eye treatment agent that can be used in combination is selected from Acular (ketorolac tromethamine ophthalmic solution) 0.5%, Acuvail (ketorolac tromethamine), AK-Con -A (naphazoline ophthalmic), Akten (lidocaine hydrochloride), Alamast, Alphagan (brimonidine), Alrex, Astepro (azelastine hydrochloride nasal spray), AzaSite (azithromycin), Bepreve (benzene Bepotastine Sulfonate Ophthalmic Solution), Besivance (Besifloxacin Ophthalmic Suspension), Betaxon, BSS Sterile Irrigation Solution, Cosopt, Durezol (Difluprednate), Eylea (Aflibercept), Lotemax, Lucentis (ranibizumab), Lumigan (bimatoprost ophthalmic solution), Macugen (pigatanib), Ocuflox (ofloxacin ophthalmic solution) 0.3%, OcuHist, Ozurdex (dexamethasone) , Quixin (levofloxacin), Rescula (unoprostone isopropyl ophthalmic solution) 0.15%, Restasis (cyclosporine ophthalmic emulsion), Salagen tablets, Travatan (travoprost ophthalmic solution), Valcyte ( Valganciclovir Hydrochloride), Trifluridine (Viroptic), Vistide (Cidofovir), Visudyne (Verteporfin for Injection), Vitrasert Implant, Fomivirxen Injection, ZADITOR, Zioptan (He Fluprostin Ophthalmic Solution), Zirgan (Ganciclovir Ophthalmic Gel), Zymaxid (Gatifloxacin Ophthalmic Solution), Atropine, Flurbiprofen, Physostimine, Azopt ), gentamicin, pilocarpine (Proparacaine), bacitracin, hypromellose eye solution (Goniosol), polymyxin B, povidone iodine (Betadine), gramicidin, prednisone Dragon, Betaxolol, Humorsol, Proparacaine, Betaxolol Eye Drops (Betoptic), Hylartin, Propine, Brinzolamide, Hypertonic NaCl, Puralube, BSS, Indocycanine Green, Rose Bengal, Carbachol, Itraconazole, Sodium Hyaluronate, Cefazolin, Latanoprost, Suprofen, Celluvisc, Mannitol, Oxytetracycline, Chloramphenicol , Methazolamide, Timolol, Ciloxan, Miconazole, Tobramycin, Ciprofloxacin, Miostat, Triamcinolone, Cosopt, Muro 128, Trifluridine, Demecarium, Neomycin, Tropone Piracamide, Dexamethasone, Methazolamide (Neptazane), Trusopt, Dipiforin, Ocuflox, Vidarabine, Dorzolamide, Ofloxacin, Vira-A, Epinephrine, Oxytetracycline, Trifluorothymidine, Fluorescein, Phenylephrine, and Xalatan.

Herein, inhibiting, preventing or reversing dysfunction does not require 100% inhibition, prevention, eradication or reversal. An "effective amount" of an ophthalmic pharmaceutical composition of this type of natural product is an amount that inhibits, prevents or reverses said various ophthalmic diseases in a subject. The ophthalmic pharmaceutical compositions of the present invention are administered to a subject in need thereof in an amount effective to treat visual disorders. As used herein, "therapeutically effective amount" means a dose that alleviates at least one of the signs, symptoms, or causes of the various ophthalmic diseases or any other desired alteration of the biological system in an individual. In prophylactic applications, the term "prophylactically effective amount" means a dose administered to patients susceptible to or at risk of a particular disease, which may be the same or different than the therapeutically effective amount. The effective amount of the composition for a particular individual may depend on the individual, the severity of the individual's condition, the type of formulation administered, the frequency of dosing and the duration of treatment. According to the present invention, even if the ophthalmic pharmaceutical preparation of the present invention is administered at a relatively low concentration, for example, any concentration within 10 ⁻⁹ M to 10 ³ M in liquid drops, it can be administered by only once, twice, Three or more applications reverse such visual disturbances, and so quickly.

Further, the notoginsenoside extract is selected from the group consisting of notoginsenoside R1, notoginsenoside R2, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rd, ginsenoside Rf, One or more of ginsenoside Rc, ginsenoside Rh1 and escin IX.

Preferably, the notoginsenoside extract contains the following components with a total content of 60-90%: notoginsenoside R1, notoginsenoside R2, ginsenoside Rg1, ginsenoside Rg2, ginsenoside Re, ginsenoside Rb1, ginseng Saponin Rb2, Ginsenoside Rd, Ginsenoside Rf, Ginsenoside Rc, Ginsenoside Rh1 and Aescin IX.

Further preferably, in the notoginsenoside extract, the content of notoginsenoside R1 is more than 3.0%, the content of ginsenoside Rg1 is more than 20.0%, the content of ginsenoside Re is more than 1.5%, and the content of ginsenoside Rb1 is more than 25.0%, The content of ginsenoside Rd is more than 2.5%.

The sources of medicinal materials for the extract of notoginseng saponins include but not limited to notoginseng, ginseng and American ginseng. Wherein, Radix Notoginseng is selected from the dried roots, rhizomes, stems, flowers and fruits of Panax notoginseng (Burk.) F.H Chen, a plant of the family Araliaceae.

Said medicine can use notoginseng saponin extract as the only active ingredient. Wherein, the mass percent content of notoginsenoside extract is 0.02-30.0%, preferably 0.1-10.0%, and the remaining 60.0-99.9% is pharmaceutically acceptable carrier and/or auxiliary material.

The pharmaceutically acceptable carrier is water, buffer or sodium chloride solution. In some embodiments, the pharmaceutically acceptable carrier is sterile. In other embodiments, the pharmaceutically acceptable carrier is an ointment. In other embodiments, the pharmaceutically acceptable carrier is a gel. Gels can be formulated using gel formulation materials known in the art.

The notoginseng saponin extract in the present invention can also be replaced by its corresponding pharmaceutically acceptable free acid, free base, salt (for example, acid or base addition salt), hydrate or prodrug, etc. The "pharmaceutically acceptable salt" or "pharmaceutically acceptable acid" refers to the pharmaceutically acceptable organic or inorganic salt or acid of this type of natural product, respectively. The counterion can be any organic or inorganic moiety that stabilizes the charge on the parent compound. Furthermore, a pharmaceutically acceptable salt (or acid) can have more than one charged atom in its structure. Examples where multiple charged atoms are part of a pharmaceutically acceptable salt (or acid) can have multiple counter ions. Thus, a pharmaceutically acceptable salt (acid) may have one or more charged atoms and/or one or more counterions.

Pharmaceutical compositions can also be prepared by dissolving the composition of the present invention in an appropriate solvent. Suitable solvents include, but are not limited to, water, saline solutions (eg, NaCl), buffer solutions, ointments, gels, or other solvents. Aqueous solutions and diluents for suspensions used in the preparation of eye drops may include distilled water, physiological saline and the like. These pharmaceutical compositions can be formulated in the following manner: Compounds are optionally mixed with appropriate pharmaceutical additives such as excipients, disintegrants, binders, lubricants, diluents, buffers, preservatives, wetting agents, Agents, emulsifiers, dispersants, stabilizers and dissolution aids are mixed, diluted or dissolved, and formulated in a conventional manner according to the dosage form. Various additives may be contained in the eye drops, ophthalmic gel and/or ophthalmic ointment as required. These additives may include additional ingredients, additives or carriers suitable for use in or around the eye without undue toxicity, incompatibility, instability, irritation, allergic response, and the like. Additives such as solvents, bases, solubilizers, suspending agents, thickeners, emulsifiers, stabilizers, buffers, isotonicity regulators, pH regulators, chelating agents, soothing agents, Preservatives, flavoring agents, flavoring agents, colorants, excipients, binders, lubricants, surfactants, absorption promoters, dispersants, preservatives, solubilizers, etc.

For example, eye drops can be formulated by dissolving the compound in sterile water dissolved in a surfactant and optionally adding appropriate pharmaceutical additives such as preservatives, stabilizers, buffers, antioxidants and viscosity improvers. For example, buffers are added to keep the pH constant, and the buffers may include pharmaceutically acceptable buffers such as borate buffers, citrate buffers, tartrate buffers, phosphate buffers, and the like. In addition to buffers, isotonic agents may be added to eye drops to make preparations isotonic with tear fluid. Isotonic agents include, but are not limited to, sugars, polyols, and salts. The isotonic agent is added in such an amount that the osmotic pressure of the eye drops is equal to that of tear fluid. Preservatives may be added to maintain the integrity of the eye drops and/or ophthalmic ointments. In some embodiments, thickeners are used to increase the viscosity of ophthalmic formulations, such as eye drops, ophthalmic gels, and/or ophthalmic ointments. Eye drops, ophthalmic gels and/or ophthalmic ointments may be prepared by aseptic manipulation or alternatively sterilized at a suitable stage of manufacture. For example, sterile pharmaceutical compositions can be prepared by aseptically admixing sterile ingredients. Alternatively, the sterile pharmaceutical composition can be prepared by admixing the ingredients followed by sterilization of the final formulation. Sterilization methods may include, but are not limited to, heat sterilization, radiation, and filtration. Ophthalmic ointments (ointments) may be prepared aseptically by incorporating the active ingredient into the base used for ointment preparations, followed by formulation into a pharmaceutical formulation by any method known in the art.

Certain embodiments of the invention also relate to kits comprising components useful for the treatment and/or prevention of symptoms associated with various ophthalmic diseases. Such kits comprise a container comprising a natural product composition of the invention in a pharmaceutically acceptable carrier, and methods for administering the natural product composition of the invention for the treatment of dry eye, ocular trauma, ocular vascular disease and ocular Statement that at least one symptom related to neurological diseases and the like has been improved or prevented. The container included in some of the kits referred to herein is a dropper for administering eye drops. In other embodiments, the container is a tube for dispensing ointments or gels. In other embodiments, the container is any suitable container for drug delivery, including but not limited to a syringe or other container suitable for ocular delivery or topical administration of a drug. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods, devices and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods, devices and materials are now described.

Beneficial effects: the present invention utilizes the anti-thrombosis, microcirculation improvement, neuron survival and damage repair promotion, hemostasis and wound tissue healing activities of this type of natural product to make a dosage form specially for eye diseases. Pharmacological experiments have proved that the drug has a healing effect on damage to the eyes and vision caused by dry eye, eye trauma, ocular vascular diseases and ocular neurological diseases. At the same time, the mode of topical ocular administration adopted by the present invention has many advantages such as less dosage, high safety, less adverse reactions, and good patient compliance, avoiding the safety risks brought by injection administration, and changing the route of administration Finally, its metabolic pathway and mechanism of action are different from injections, and it has a good clinical application prospect.

Description of drawings

Fig. 1 is the optical microscopic result of embodiment 12, and wherein Fig. 1 a is retina test result, and Fig. 1 b is choroid test result;

Fig. 2 is a statistical representation of the relief of eye dryness by the drug of the present application.

Detailed ways

The present application will be described in detail below in conjunction with specific embodiments.

Example 1

This type of natural compound multi-dose eye drops (1)

Take 10 grams of this type of natural compound, dissolve it in 300 milliliters of normal saline, filter it with a 0.22 μm membrane, dilute to 1000 milliliters, seal it, sterilize it at high temperature, dispense it into eye drops bottles, each bottle is 10 milliliters, and get 100 drops eye drops.

Embodiment 2

This type of natural compound multi-dose eye drops (2)

Take 5 grams of this type of natural compound, dissolve it in 300 milliliters of normal saline, filter it with a 0.22 μm membrane, dilute to 1000 milliliters, seal it, sterilize it at high temperature, dispense it into eye drops bottles, each bottle is 10 milliliters, and get 100 drops eye drops.

Embodiment 3

This type of natural compound single-dose eye drops (1)

Take 10 grams of this type of natural compound, dissolve it in 300 milliliters of normal saline, filter it with a 0.22 μm membrane, dilute to 1000 milliliters, seal it, sterilize it at high temperature, dispense it into eye drops bottles, 0.4 milliliters per bottle, and get 25000 drops eye drops.

Embodiment 4

This type of natural compound single-dose eye drops (2)

Take 5 grams of this type of natural compound, dissolve it in 300 milliliters of normal saline, filter it with a 0.22 μm membrane, dilute to 1000 milliliters, seal it, sterilize it at high temperature, dispense it into eye drop bottles, each bottle is 0.4 milliliters, and get 25000 drops eye drops.

Embodiment five

This type of natural compound intraocular injection (1)

Take 4 grams of this type of natural compound, dissolve it in 300 milliliters of normal saline, filter it with 0.22 μm membrane, dilute to 1000 milliliters, dispense it into ampoules, 2 milliliters per bottle, seal it, and sterilize at high temperature to obtain 500 eyes injection.

Embodiment six

This type of natural compound intraocular injection (2)

Take 8 grams of this type of natural compound, dissolve it in 300 milliliters of normal saline, filter it with 0.22 μm membrane, dilute to 1000 milliliters, dispense it into ampoules, 2 milliliters per bottle, seal it, and sterilize at high temperature to obtain 500 eyes injection.

Embodiment seven

This type of natural compound intraocular injection (lyophilized)

Take this type of natural compound and make it into a lyophilized stock solution, remove the pyrogen, microfilter, subpackage, sterilize, pre-freeze in a -80°C refrigerator for 6 hours, and freeze-dry for 12 hours to obtain the lyophilized powder for intraocular injection of this type of natural compound. .

Embodiment Eight

This type of natural compound ophthalmic ointment

Take medical yellow vaseline, glycerin, and lanolin, and mix them evenly in a ratio of 8:2:1 to make an eye ointment base. Take 3000 grams of matrix, add 30 grams of this type of natural compound, and mix well to obtain this type of natural compound ophthalmic ointment, which is aseptically divided into 3 grams for each, and 1000 branches are obtained.

Embodiment nine

This type of natural compound topical eye cream

Take poloxamer 188 to emulsify, add glycerin and propylene glycol and mix evenly to make ophthalmic ointment base. Take 3000 grams of matrix, add 30 grams of this type of natural compound, and mix well to obtain this type of natural compound ophthalmic ointment, which is aseptically divided into 3 grams for each, and 1000 branches are obtained.

Embodiment ten

This type of natural compound eye lotion

According to the provisions of Chinese Pharmacopoeia Part IV lotion, take 20 grams of this type of natural compound, add water for injection to make an isotonic solution to 1000 ml, stir well, divide into 100 ml saline bottles, stopper, seal with aluminum cap, 100 °C Sterilize with circulating steam for 30 minutes.

Embodiment Eleven

Osmometry

Take the products in the above-mentioned Example 1 to Example 7 respectively, according to the provisions of the fourth part of the "Chinese Pharmacopoeia" 0632, the measured osmotic pressure is between 296.000-308.000mOsm/l.

Embodiment 12

Treatment of retinal vein thrombosis experiment

(1) Experimental animals and grouping: 7 New Zealand rabbits, divided into 3 groups, 2 rabbits in the normal group (numbered A, B), a total of four eyeballs, and the remaining 5 rabbits (numbered C, D, E, F , G), the left eye was given normal saline as the model group, and the right eye was given this type of natural compound eye drops as the administration group.

(2) Experimental materials: 1% atropine, 2% procaine, this type of natural compound eye drops, and normal saline.

(3) Viscera submitted for inspection: fundus tissues of rabbits.

(4) Examination method: Rabbits were given general anesthesia by intravenous or intraperitoneal injection of 10% chloral hydrate. After anesthesia, 5 μL of 1% atropine was instilled in the eyelids to dilate the pupil, and 5 μL of 2% procaine was added 15 minutes later for corneal anesthesia. Intravenous injection of tiger bengal 20 mg·kg-1, volume 1m L·kg, 1 min later, the retinal vein was irradiated with cold laser under the guidance of pre-operative mirror and in vitro positioner to prepare retinal vein embolism model. The normal group was not treated. The administration group was instilled with 1.25% natural compound eye drops of this type (dissolved in physiological saline) for a week, once a day, 35 μl each time, and the model group was given normal saline in parallel. After the experiment was over, the eyeballs were dissected, fixed and collected, dehydrated, embedded in paraffin, made into slices (4 μm thick), stained with HE, and observed the retina and choroid under an optical microscope to check whether there were lesions, the type and degree of lesions.

(5) Examination results: the results are shown in Figure 1a and Figure 1b. According to the illustrations, the edema of the inner core layer disappeared, the vacuoles decreased, and the nuclear pyknosis phenomenon was alleviated in the administration group; the thrombus in the choroidal vessels disappeared or became smaller. It can be seen that this product has a good therapeutic effect on experimental retinal vein embolism.

Embodiment Thirteen

Relieve dry eye syndrome experiment 1

(1) Experimental method: sodium fluorescein labeling method or tear fluid qualitative and quantitative analysis method (under conditions) to initially characterize the ocular pharmacokinetic behavior of this product.

(2) Experimental animals and grouping: 4 New Zealand rabbits, divided into 4 groups, the left and right eyes of each rabbit were divided into one group (numbered A, B, C, D), the left eye was given normal saline as the model group, and the right eye was given This type of natural compound eye drops is the administration group.

(3) Experimental materials: this type of natural compound eye drops, physiological saline.

(4) Experimental process:

Sodium fluorescein labeling method

(5) Inspection method: Each group continuously observed the strength of the fluorescent layer under the ultraviolet light at the same multiple time periods.

(6) Inspection results:

residence time A B C D Left eye (saline) 45 seconds 45 seconds 30 seconds 45 seconds Right eye (eye drops) 4 minutes 45 seconds 5 minutes 30 seconds 5 minutes 30 seconds 4 minutes 30 seconds

According to the above statistics, the ocular surface residence time of this type of natural compound eye drops is more than five times that of normal saline, the bioavailability is high, the stability of the tear film is significantly increased, and the dryness of the ocular surface is relieved.

Embodiment Fourteen

Relieve dry eye syndrome experiment 2

(1) Experimental method: trial experience survey

(2) Experimental materials: this type of natural compound eye drops, Zhenshiming eye drops

(3) Trial personnel: 45 people with an equal ratio of male to female, aged between 18 and 60 years old, and who have not used eye preparations recently. The trial participants were divided into two groups, namely the short-term trial group and the long-term trial group. Among them, the short-term trial group 40 people in the group and 5 people in the long-term trial group.

(4) Experimental process:

1. Short-term trial group: Trial users use this product after staring at the electronic product screen for a long time and feel uncomfortable, and fill out the questionnaire several times after the same interval, including whether it is comfortable to use, whether there is stimulation, whether it improves visual fatigue, Whether there are side effects, etc.

2. Long-term trial group: According to the trial situation of the short-term group trial users, the long-term group trial users use this product for a long time within one month, follow up with them, understand the effectiveness of this product, and ensure the drug safety of the trial users.

(5) Survey results of the trial users:

1. After trying this type of natural compound eye drops, the effect of relieving dry eye syndrome is strong, and the feeling of use and compliance are good at the same time. The statistical results are shown in the following table:

Proportion of volunteers who mentioned in the evaluation that symptoms of visual fatigue were relieved 91.67% Proportion of volunteers who mentioned in the evaluation that visual fatigue symptoms were significantly relieved 58.33% Proportion of volunteers willing to use the product again 87.50%

The observed index symptoms: blurred vision, eye muscle soreness, eye dryness, strange secretions, eye burning sensation, eye itching, foreign body sensation in the eyes, tears, etc.; the items are described by scoring, Divided into 0-5 points, 0 points as no symptoms, 1-2 points as mild symptoms, 3-4 points as obvious symptoms, 5 points as severe symptoms; ANOVA analysis was performed on the feedback information of volunteers, P<0.05 For remission, P<0.01 was significant remission.

2. Figure 2 shows the statistics on the effect of using the eye drops of this application to relieve eye dryness. According to the diagram, it can be seen that after using this type of natural compound eye drops for a period of time, eye dryness can be significantly 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.