CN108524448A - A kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application - Google Patents
A kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application Download PDFInfo
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Abstract
The present invention provides a kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application.The euphadienol anti-cataract eye-drops preparations contain in the form of alone or in combination existing for euphadienol, can also contain surfactant and the cosolvent with medicinal ophthalmology auxiliary material.Wherein, the nano particle size of the euphadienol is 20 100 nanometers.Eye-drops preparations of the present invention has cataract fine curative effect, it can be used for the treatment of different times cataract, especially suitable for initial stage cataract of old people, mild diabetes cataract or complicated cataract patient, the physiological function of human body can be improved, it can accelerate anterior ocular segment blood fortune cycle and Nutrition and Metabolism, improve the permeability of lens capsule, restore its physiologic barrier effect, effectively control lenticular opacities promote muddy absorb.
Description
Technical field
The invention belongs to field of medicaments, more particularly to a kind of euphadienol anti-cataract eye-drops preparations and preparation method thereof
And purposes.
Background technology
Cataract is most important diseases causing blindness, in the world because cataract blinding person is up to 50% (1,700,000).With mankind's longevity
Life extends, and aging is growing day by day, because cataract blinding person will also be multiplied.At present the whole nation eyes correct defects of vision 0.3 it is white
Cataract or glaucoma patient is about 5,000,000 people, is accumulated every year with increasing 400,000~1,200,000 cataract patients newly, 75 years old Chinese or more old
The illness rate of human cataracts is up to 91%, occupies the first place of China's diseases causing blindness.Cataract is worldwide prevented at this stage
Measure is still main measure of recovering lost eyesight with operation or implantable artificial crystal, but because operation preferably opportunity is cataract mature period, because
This, patient needs to endure the torment of prolonged cataract progression of the disease, and operation is limited by condition and equipment, expense
It is more expensive, it is difficult to solve the demand of cataract patient growing day by day.Therefore, the prevention of cataract is carried out using drug and controlled
Treating has important Social benefit and economic benefit.
Cataract is one of most common causes of blindness, is the common disease for seriously affecting human health, frequently-occurring disease.Currently,
Cataract there is no definite effective drug treatment.The pathogenesis of cataract is not yet disclosed completely so far.Cataract
It is the elderly and the most commonly seen eye disease of diabetes patient.The reason of causing cataract by it is different, cataract can be divided into it is senile,
Concurrency, traumatic, Poisoning, dysbolism etc. are several.Clinical research shows in all kinds of cataract cases, by aging
Caused cataract of old people occupies most ratios.Cataract of old people is eyes disease, but two morbidities can have successively.
The position initially formed according to cataract, cataract of old people are divided into cortical cataract (Corticsalcataract), nuclearity
Cataract (Nuclearcataract) and capsular cataract (Subcapsular Cataract), wherein cortical cataract is
The most common type of cataract of old people.The main reason for cataract of old people is the elderly's visual impairment, the disease mainly show
It is muddy to gradually appear denaturation during crystal aging, also known as become cataract.
Although the cause of disease about cataract is there are a variety of theories, such as crystalline lens lesion opinion, on lens capsule and crystalline lens
Skin variation opinion, ciliary epithelium variation opinion is aqueous humor variation opinion etc., but is not proved yet also so far.
Compare with limiting used in the medication amount of Ocular Drug Delivery system, a part can cause drugs through skin table
Layer, the huge obstacle of the retina in rock matter cuticula and eyes.The drug that uniquely can pass through these obstacles, which is those, to be had not
Co-extensive and the perfect specific combination of physicochemical characteristics height, for example, extend the residence time and special target drug conveying it is micro-
Ball and nanotechnology.
The formation basic theory and its Study of Etiology of cataract：
Lenticular function is to focus light rays to generate vision on retina.Lenticular main component is water and protein,
The 80% ~ 90% of crystalline lens dry weight is protein, and the protein includes tri- big nation's crystalline protein of A, E and Y.It is lenticular
Lightness is kept by the metabolism of constant moisture, the protein of high concentration and complexity, i.e. each protein
Structure and they between interaction be maintain the crystalline lens transparency molecular basis；That is, crystalline protein
Ordered arrangement be maintain crystalline lens space structure material base, i.e., if crystalline protein composition change, can influence,
Destroy such normal configuration.
During crystalline lens growing, crystalline protein is by the aging of body own nature and the shadow of many extraneous factors
It rings, it may occur that the quality and quantity of different modification denaturation crystalline proteins can change, and it is insoluble that water-soluble components are constantly changed into water
Property ingredient, influence its water solubility, and then influence lenticular normal configuration and translucency, eventually lead to the shape of cataract of old people
At.That is, in human aging process, once the protein structure in crystalline lens is destroyed, then crystalline lens is by clear
The clear transparent muddiness that becomes is opaque, and then influences lenticular normal configuration and translucency, and gradually develops into senile white interior
Barrier.
Lenticular translucency depends primarily on the quality and quantity of water-solubility protein component in crystalline lens, especially several masters
The structural proteins wanted such as EB2 is (referring to document Aarts HJ, Lubsen NH, Schoenmakers JG.. Crystallin
Gene Expression During Rat Lens Development. Eur J Biochem, 1989,183 (1): 31-
36), 5 Y, 6 (Y C, Y D), Yw, Y2,3 and chaperone AA2 and 0lB2.The change of the quality and quantity of water-soluble crystalline protein,
Directly affect the formation of the translucency and cataract of crystal.
Therefore, lenticular translucency is maintained, on the one hand, the amount of water-solubility protein enough in crystalline lens need to be kept, this
The gene for depending primarily on internal body crystalline protein is not subjected to be mutated, and can implement normal expression, such as needs certain crystalline substance
Body protein carries out high expression or low expression, then gene engineering method can be used, activate or inhibit corresponding gene；On the other hand,
It needs to contain as possible, slow down transformation of the crystalline protein from water-solubility protein to water-insoluble protein.
The translucency of crystal not only needs the water-soluble components of sufficient amount to maintain, but also also needs to consider lenticular spy
Different metabolic way.From crystalline protein self-generating, constantly squeezed to the core of crystal by the crystalline protein of rear generation, and store up
There are different crystal structure layers.Therefore, no matter water-solubility protein component or water-msoluble ingredients, can not be metabolized body
Outside.But the accumulation of water-soluble components helps to build the normal configuration of crystal layer from inside to outside；And water-insoluble composition is gradually
Secondary accumulation then can gradually increase the light scattering of crystal, be unfavorable for translucency, that is to say, that it is cataract of old people formation
Material base.
The current treatment status of cataract：
Cataract is worldwide blinding disease.In terms of clinic diagnosis, it is for unique effective treatment means of cataract at present
Surgical operation.Although cataract operation has become better and approaching perfection day by day, inevitable postoperative complication and socioeconomic problem are still very
Seriously, such as after operation After Cataract, secondary glaucoma or corneal injury incidence are higher in the several years, are generally difficult to root
It removes.
Effective prevention and drug treatment are found, early stage controls cataract, is still the research hotspot in the field.In advance
There are mainly two types of approach for anti-and drug therapy cataract, that is, reduce the risk factor of pathogenesis of cataract and apply antiuveitis
Object.There are diabetes, glaucoma, myopia, prolonged application corticosteroid, serious with the relevant Major Risk Factors of pathogenesis of cataract
Diarrhea, ultraviolet radiation, heavy drinking and smoking etc..In terms of medicinal application, existing the sixth of the twelve Earthly Branches develops tens of kinds of drugs and is used for clinic,
For maintaining the translucency of crystal to delay or treat cataract.Due to lacking the perfect foundation for cataract formation mechanism, grind
Make and still in all drug used, there are still many defects, such as it is efficient it is relatively low, specific aim is poor etc..Therefore, although name
The numerous anti-cataract medicines of mesh still have many problems in countries in the world extensive use.The drug therapy of cataract is still
Stern challenge so is faced in spite of tens of kinds of anti-cataract medicines by extensive Clinical practice, but proves its validity
Positive evidence is very few.Due to cataract be various factors synthesis as a result, its pathogenic factor not yet come to a conclusion.Currently,
Each scientific research organization be mostly be directed to eye in a certain pathogenic factors, or confrontation pathogenic process certain physiological acoustic signals carry out it is anti-white
The research and development of cataract or glaucoma drug.
The trend of cataract therapy drug research：
Cataract is synthesis result caused by multifactor collective effect, and pathological change is multilevel multi-level.
With the continuous improvement of research means, research pathogenetic to cataract also will increasingly be goed deep into, while to treating cataract medicine
The exploitation specific aim of object is also stronger.Ideal cataract therapy drug should be able to restore the eubolism of crystal and promote brilliant
The absorption of body muddiness, but there is no a medicine that can reach above-mentioned requirements up to now, nevertheless, any promising inhibition is white
The measure of cataract or glaucoma morbidity all shows the value of research.
Euphadienol is tetracyclic triterpenoid, and the Chinese medicine root of gansui and Beijing spurge root are mostly using the compound as reference substance at present
To establish quality standard.Beijing spurge root, the root of gansui belong to the root drug of Euphorbiaceae Euphorbia, and are classified as on tcm clinical practice
Drastically purgating water drug, for treating the cards such as oedema turgor, chest and abdomen ponding, phlegm and retained fluid accumulation.Wherein the root of gansui (Kanui Radix) is the root of Beijing euphorbia
The dried root of section's euphorbia root of gansui (Euphorbia kansui T.N.Liou ex T.P.Wang), main product in Shaanxi,
The ground such as Henan, Shandong, Gansu are one of common toxic traditional Chinese medicine materials, before the medicinal record of the root of gansui can trace back to 2000
《Sheng Nong's herbal classic》.The root of gansui is cold in nature, bitter, toxic, and return lung, kidney, large intestine channel have effects that removing water retention by purgation；And Beijing spurge root is
The dry root of the Euphorbiaceae euphorbia root of Beijing euphorbia (E. uphorbiap ekinensis Rupr), is China's traditional Chinese medicine, records
In going through version《Chinese Pharmacopoeia》, there is the effect of removing water retention by purgation, dispersing swelling and dissipating binds.Modern clinic is usually used in cirrhotic ascites and a variety of
Hydrothorax caused by reason.
Euphadienol significantly can inhibit mouse skin carcinogeneis to act on, and also have induced labor effect；Recent studies have shown that
Euphadienol can prevention of postoperative intestinal adhesion, prepared drug can make patient's gut function quickly greatly restore, feed in advance, and
The medicine has no adverse reaction.
The existing pertinent literature report for preparing euphadienol reference substance, in Chinese medicine Beijing spurge root, euphadienol contains
Amount is higher, and mass fraction accounts for about 1%.Euphadienol is prepared using separation methods such as silica gel column chromatography, gel chromatography, recrystallizations
Chemical reference substance simultaneously carries out standard substance research.[Ge Xiuyun, Sun Lili, Zhang Lelin, euphadienol reference substance in Beijing spurge root
Preparation research, China Dispensary, 2015,26（27）：3831-3833], while also having patent [a kind of system for preparing euphadienol
The method of standby euphadienol, CN201310168250.1], using root of gansui medicinal material through alcohol extracting, through extraction, silica gel post separation,
Reversed-phase high performance liquid chromatography prepares three step efficiently purifyings, can get the euphadienol sterling that purity is more than 98%.
Currently, there has been no the reports that document report treats cataract and related ophthalmology disease with euphadienol.
Invention content
The object of the present invention is to provide a kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application.Institute
Eye-drops preparations is stated using euphadienol as active material, has fine curative effect to prevention and treatment cataract, when can be used for different
The treatment of phase cataract is suffered from especially suitable for initial stage cataract of old people, mild diabetes cataract or complicated cataract
The physiological function of human body can be improved without operation in person, can accelerate anterior ocular segment blood fortune cycle and Nutrition and Metabolism,
The permeability for improving lens capsule, restores its physiologic barrier effect, effectively controls lenticular opacities, promotes muddy absorb.
The purpose of the present invention is what is be achieved through the following technical solutions：
A kind of eye-drops preparations, the eye-drops preparations contain in the form of alone or in combination existing for euphadienol.
Further, the cosolvent in the eye-drops preparations also containing surfactant and with medicinal ophthalmology auxiliary material.
Further, the nano particle size of the euphadienol is 20 ~ 100 nanometers.
Further, in the eye-drops preparations euphadienol a concentration of 0.01 ~ 2.5% (weight/volume).
Further, the euphadienol can be natural euphadienol, can also be the euphadienol of synthesis；
The natural euphadienol comes from a variety of Euphorbiaceae natural drugs, such as the root of gansui, Beijing spurge root；The synthesis root of Beijing euphorbia diene
Alcohol is from approach such as chemical synthesis and biosynthesis.
Further, the surfactant is Tween 80, polysorbas20, macrogol ester, polyethylene glycol, lecithin and sweet
The mixture of one or more of oily ether.
Further, the cosolvent is nonionic cosolvent, specially ethyl alcohol or polyalcohol, such as polyethylene glycol or
Polypropylene glycol.
Further, the medicinal ophthalmology auxiliary material be polymer, chelating agent, stabilizer, reinforcing agent, buffer, preservative,
The mixture of one or more of thickener and complexing agent.
Further, the polymer is water-soluble polymer, including methylcellulose, hydroxyethyl cellulose, hydroxypropyl
Base cellulose, hydroxypropyl methyl cellulose, Hydroxypropyl ethyl cellulose, sodium carboxymethylcellulose, polyvinyl alcohol, polyvinyl pyrrole
Alkanone, polyethylene glycol is poly- (methyl methacrylate), polycarbophil, gelatin, and sodium alginate is poly- (acrylic acid), polyethylene oxide
With chitosan or a kind of their derivative.
Further, the chelating agent is the two of EDTA to receive salt.
Further, the stabilizer is sodium hydrogensulfite, glycerine, sodium citrate, to hydroxybutyl, benzalkonium chloride, according to
Ground acid or its pharmaceutically acceptable salt, vitamin E or derivatives thereof, the mixture of one or more of natrium adetate.
Further, the isotonic agent is selected from sodium chloride, potassium chloride, PEARLITOL 25C, glucose, glycerine, xylitol and third
The mixture of one or more of alkene.
Further, the thickener is selected from methylcellulose, ethyl cellulose, hydroxypropyl methyl cellulose, polyethylene
The mixture of one or more of pyrrolidones, polyvinyl alcohol, sodium chondroitin sulfate, Sodium Hyaluronate and chitosan.
Further, the preservative is selected from sodium hydrogensulfite, niter cake, sodium thiosulfate, benzalkonium chloride, chloro fourth
The mixture of one or more of alcohol, thimerosal, phenylester, phenyl nitrate, methyl esters, polyvinyl alcohol and benzyl carbinol.
Further, the buffer includes sodium carbonate, sodium tetraborate, sodium phosphate, sodium acetate, one kind in sodium bicarbonate
Or several mixture.
Further, further include colloidal drug carriers in the eye-drops preparations.
Further, the dosage form of the eye-drops preparations includes eyedrops and eye glue.
Further, the preparation method of the eye-drops preparations includes the following steps：The euphadienol and surface are lived
Property agent, cosolvent mixing；Rotary evaporation in vacuo removes cosolvent, and film-form is made；Buffer salt solution aquation is added and obtains halberd two
Enol liposome turbid liquor.
It is another object of the present invention to what is be achieved through the following technical solutions：
Purposes of the euphadienol in preparing anti-cataract disease product, the cataract conditions be include cataract of old people
And its one or more diseases including relevant disease, cortical cataract and its relevant disease.
The present invention having the beneficial effect that compared with prior art：
1, present invention firstly discovers that and specify euphadienol for cataract and its relevant disease have good prevention and
Therapeutic effect has easy to use, significant effect, and the features such as have no adverse reaction；
2, cataract is global first diseases causing blindness, and global tens of millions of people suffers from cataract, currently the only this degeneration for the treatment of
The method of eye illness is to perform the operation, although the relatively simple safety of cataract operation, with the aging of population, needs within following 20 years to connect
The number performed the operation will double, and for many people, and operation price is still excessively high, it is difficult to bear；It is of the present invention ophthalmically acceptable
The physiological function of human body can be improved under the premise of without operation in preparation, can accelerate anterior ocular segment blood fortune cycle and nutrition generation
It thanks, improves the permeability of lens capsule, restore its physiologic barrier effect, effectively control lenticular opacities, promote muddy absorption, phase
Than the mode of existing common surgical cataract, medical expense is not only reduced, and easy to use, significant effect；
3, compared with existing anti-cataract medicine, present invention firstly discovers that euphadienol, which has, significantly improves cataract symptom,
Protein denaturation in crystalline lens can be prevented simultaneously and assembles agglomerating, while the mode as eye drops is administered, safer
Effectively；
4, the present invention derives from natural plants, one time toxic side effect is small using euphadienol as active constituent, it is easier to suffer from
Person is received；
5, it is mid-aged population that eye-drops preparations of the present invention, which is mainly suitable for object, selects eye drops for preventing, then daily
Eye drip is primary, inhibits albuminous degeneration, delays crystal aging, control cataract of old people in initial phase.
Description of the drawings
Fig. 1 is the structural schematic diagram of euphadienol.
Specific implementation mode
The following examples can further illustrate this patent, but the present invention by next example retouching in detail
State the preparation and application of the further clear present invention.These technologies being interpreted as in the literature include raw material and method
There are many variations, it is also without departing from the scope of the invention, also it is not in any way limit the scope of the present invention.
Embodiment 1
Present embodiments provide it is a kind of prevention and treatment cataract and associated ophthalmopathy eye-drops preparations, the eye-drops preparations contain with
Euphadienol existing for form alone or in combination.
Further, the cosolvent in the eye-drops preparations also containing surfactant and with medicinal ophthalmology auxiliary material,
Described in active constituent be euphadienol.
Further, the nano particle size of the euphadienol is 20 ~ 100 nanometers.
Further, in the eye-drops preparations euphadienol a concentration of 0.01 ~ 2.5% (weight/volume).
Further, the euphadienol can be natural euphadienol, can also be the euphadienol of synthesis；
The natural euphadienol comes from a variety of Euphorbiaceae natural drugs, such as the root of gansui, Beijing spurge root；The synthesis root of Beijing euphorbia diene
Alcohol is from approach such as chemical synthesis and biosynthesis.
Further, the surfactant is Tween 80, polysorbas20, macrogol ester, polyethylene glycol, lecithin and sweet
The mixture of one or more of oily ether.
Further, the cosolvent is nonionic cosolvent, specially ethyl alcohol or polyalcohol, such as polyethylene glycol or
Polypropylene glycol.
Further, the medicinal ophthalmology auxiliary material be polymer, chelating agent, stabilizer, reinforcing agent, buffer, preservative,
The mixture of one or more of thickener and complexing agent.
Further, the polymer is water-soluble polymer, including methylcellulose, hydroxyethyl cellulose, hydroxypropyl
Base cellulose, hydroxypropyl methyl cellulose, Hydroxypropyl ethyl cellulose, sodium carboxymethylcellulose, polyvinyl alcohol, polyvinyl pyrrole
Alkanone, polyethylene glycol is poly- (methyl methacrylate), polycarbophil, gelatin, and sodium alginate is poly- (acrylic acid), polyethylene oxide
With chitosan or a kind of their derivative.
Further, the chelating agent is the two of EDTA to receive salt.
Further, the stabilizer is sodium hydrogensulfite, glycerine, sodium citrate, to hydroxybutyl, benzalkonium chloride, according to
Ground acid or its pharmaceutically acceptable salt, vitamin E or derivatives thereof, the mixture of one or more of natrium adetate.
Further, the isotonic agent is selected from sodium chloride, potassium chloride, PEARLITOL 25C, glucose, glycerine, xylitol and third
The mixture of one or more of alkene.
Further, the thickener is selected from methylcellulose, ethyl cellulose, hydroxypropyl methyl cellulose, polyethylene
The mixture of one or more of pyrrolidones, polyvinyl alcohol, sodium chondroitin sulfate, Sodium Hyaluronate and chitosan.
Further, the preservative is selected from sodium hydrogensulfite, niter cake, sodium thiosulfate, benzalkonium chloride, chloro fourth
The mixture of one or more of alcohol, thimerosal, phenylester, phenyl nitrate, methyl esters, polyvinyl alcohol and benzyl carbinol.
Further, the buffer includes sodium carbonate, sodium tetraborate, sodium phosphate, sodium acetate, one kind in sodium bicarbonate
Or several mixture.
Further, further include colloidal drug carriers in the eye-drops preparations.
Further, the dosage form of the eye-drops preparations includes eyedrops and eye glue.
Further, the preparation method of the eye-drops preparations includes the following steps：The euphadienol and surface are lived
Property agent, cosolvent mixing；Rotary evaporation in vacuo removes cosolvent, and film-form is made；Buffer salt solution aquation is added and obtains halberd two
Enol liposome turbid liquor.
Purposes of the euphadienol in preparing anti-cataract disease product, the cataract conditions be include senile white
One or more diseases including cataract or glaucoma and its relevant disease, cortical cataract and its relevant disease.
Unit of weight used in the present embodiment is kilogram, or gram；
Each raw material described in the present embodiment is the conventional products sold in the market；
In the present embodiment, each raw material can in the ratio range provided flexible combination, do not enumerate one by one herein.
Embodiment 2
The present embodiment is the preferred embodiment on the basis of embodiment 1, a kind of euphadienol nanometer eye drip provided in this embodiment
Liquid, euphadienol nano eye drop liposome is prepared using film dispersion method, is with entrapment efficiency determination result using Orthogonal Method
Optimizing index, preparation prescription are as follows：200 mg of euphadienol, 3000 mg of lecithin, appropriate absolute ethyl alcohol, phosphate-buffered
100 milliliters of liquid (phosphate buffered saline, PBS) (pH value 7.0)；By the euphadienol of recipe quantity, lecithin
Fat is dissolved in absolute ethyl alcohol, and in 40 DEG C of vacuum rotatings at thin film, rotary evaporation to no ethanol flavor is added 100 milliliters
PBS (pH value 7.0), aquation is up to euphadienol liposome turbid liquor.Euphadienol liposome particles form rule obtained
Then, it is round or oval, for 76.4% particle diameter distribution between 110~200 nm, average grain diameter is 145.2 nm, and encapsulation rate is
90.02%.Liposome eye drops obtained enclose ampoule, are put into 4 DEG C of refrigerators and preserve for use.
Embodiment 3
The present embodiment is the preferred embodiment on the basis of embodiment 1, a kind of euphadienol nanometer eye drip provided in this embodiment
Liquid, euphadienol nano eye drop liposome is prepared using film dispersion method, is with entrapment efficiency determination result using Orthogonal Method
Optimizing index, preparation prescription are as follows：1000 mg of euphadienol, 15000 mg of lecithin, appropriate absolute ethyl alcohol, phosphate are slow
500 milliliters of fliud flushing (phosphate buffered saline, PBS) (pH value 7.0)；By the euphadienol of recipe quantity, ovum
Phosphatide is dissolved in absolute ethyl alcohol, and in 40 DEG C of vacuum rotatings at thin film, rotary evaporation to no ethanol flavor is added 500 milliliters
PBS (pH value 7.0), aquation is up to euphadienol liposome turbid liquor.Euphadienol liposome particles form rule obtained
Then, it is round or oval, 77.8% particle diameter distribution is between 110~200 nm, average grain diameter 145.5nm, and encapsulation rate is
92.16%.Liposome eye drops obtained enclose ampoule, are put into 4 DEG C of refrigerators and preserve for use.
In order to show that have therapeutic effect of the drug of the present invention to cataract, the present invention have carried out pharmacological evaluation below：
Material：
Reagent N a2SeO3, it is Beijing chemical reagents corporation product (purity>97%), molten at 2 mmol/L with normal saline
Liquid；Euphadienol liposome eye drops are the product for preparing embodiment 2, a concentration of 2 mg/ml；Pirenoxine eye drops
(pirenoxine eye drops, PED, trade name card woods are excellent), for Japanese Santen Pharmaceutical Co. Ltd. product.
Model foundation：
Be born 12 d SD suckling mouses, and 25~30 g do not widen the view, provided by Chinese Academy of Medical Sciences's Experimental Animal Center.Bibliography
[Shearer T R, Ma H, Fukiage C, et a1.Selenite nuclear cataract：review of the
Model [J] .Mol Vis, 1997,3：8.] method suckling mouse row is subcutaneously injected, inject 1 time 0.2 ml/ time, be total to every other day
Meter 3 times, about 210 μ g of integral dose；Inject 3 Na2SeO3(18 d of age of mouse) afterwards, 90% or more rat can occur selenium in vain in
Barrier；Suckling mouse periodically carries out mydriasis slit lamp examination crystalline lens after widening the view, record classification results.Hereafter 15 d or so, such as without
Pharmaceutical intervention, it is muddy that 90% or more modeling rat can develop into fully crystalline body.
Animal pattern is grouped and pharmaceutical intervention
Inject Na2SeO3Brood experimental rat left eye is set as control group (n=13) by the 6th day afterwards (18 d of age of mouse), and right eye is made
For pharmaceutical intervention group (n=13).(left eye drips physiological saline to 4 times/d of eye drip；Right eye drips 2mg/mL euphadienol liposome eye drips
Liquid), every eye 1 drips (about 40 μ l) every time, continuous medication 3 weeks, periodically to rat eyes mydriasis, slit lamp examination is carried out, with trip
Scale (minimum scale value be 0.02 mm) is close to diameter change (the irregular patch of the crystalline bulk measurement nuclearity muddiness patch of suckling mouse
Take maximum gauge).It is carried out within 4 weeks after injection, hereafter because of Na2SeO3Strong toxic effect, rat model eventually develops into entirely
Cataract.
Separately take of the same age, not brood selenite induced catatract suckling mouse, be set to euphadienol liposome eye drops (n=60),
Pirenoxine (PDE, n=20) intervention group and saline control group (n=45) use 2 mg/mL euphadienol lipids respectively
Body eye drops, Japan's production Pirenoxine eye drops.4 times/d of eye drip (drips identical drug or physiology salt with group suckling mouse images of left and right eyes
Water), every eye 1 drips (about 40 μ l) every time, continuous medication 3 weeks.After timing mydriasis, with slit lamp examination rat eyes Corticism
Become, turbidity.
1 euphadienol liposome eye drops of table influence the maximum gauge variation of SD rat selenite induced catatract muddinesses plaque region
Claims (10)
1. a kind of eye-drops preparations, which is characterized in that the eye-drops preparations contain in the form of alone or in combination existing for root of Beijing euphorbia diene
Alcohol.
2. eye-drops preparations according to claim 1, which is characterized in that in the eye-drops preparations also include surfactant and
Cosolvent with medicinal ophthalmology auxiliary material.
3. eye-drops preparations according to claim 1, which is characterized in that the nano particle size of the euphadienol is 20
~ 100 nanometers.
4. eye-drops preparations according to claim 1, which is characterized in that euphadienol is a concentration of in the eye-drops preparations
0.01~2.5%。
5. eye-drops preparations according to claim 2, which is characterized in that the surfactant is Tween 80, polysorbas20, gathers
The mixture of one or more of glycol ester, polyethylene glycol, lecithin and glycerin ether.
6. eye-drops preparations according to claim 2, which is characterized in that the cosolvent is ethyl alcohol or polyalcohol.
7. eye-drops preparations according to claim 2, which is characterized in that the medicinal ophthalmology auxiliary material be polymer, chelating agent,
The mixture of one or more of stabilizer, reinforcing agent, buffer, preservative, thickener and complexing agent.
8. according to claim 1-7 any one of them eye-drops preparations, which is characterized in that the dosage form of the eye-drops preparations includes eye
Liquid medicine and eye glue.
9. a kind of preparation method of eye-drops preparations according to claims 1-8, which is characterized in that the preparation method include with
Lower step：
The euphadienol is mixed with surfactant, cosolvent；Rotary evaporation in vacuo removes cosolvent, and film is made
Shape；Buffer salt solution aquation is added and obtains halberd dienol liposome turbid liquor.
10. purposes of the euphadienol in preparing anti-cataract disease product, which is characterized in that the cataract conditions are packets
Include one or more diseases including cataract of old people and its relevant disease, cortical cataract and its relevant disease.
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| CN112315993A (en) * | 2020-12-23 | 2021-02-05 | 新疆维吾尔自治区药物研究所 | Euphorbia lipid active tetracyclic triterpene composition, and preparation method and application thereof |
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