CN106074568A - One is used for preventing and treat cataractous ophthalmic preparation and preparation method thereof - Google Patents
One is used for preventing and treat cataractous ophthalmic preparation and preparation method thereof Download PDFInfo
- Publication number
- CN106074568A CN106074568A CN201610696992.5A CN201610696992A CN106074568A CN 106074568 A CN106074568 A CN 106074568A CN 201610696992 A CN201610696992 A CN 201610696992A CN 106074568 A CN106074568 A CN 106074568A
- Authority
- CN
- China
- Prior art keywords
- sodium
- ophthalmic preparation
- preventing
- acid
- combination
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
Abstract
The present invention relates to a kind of for preventing and treat cataractous ophthalmic preparation and preparation method thereof, by weight percentage, ophthalmic preparation is made up of the lanoline alkane type tetracyclic triterpenoid of 0.1% ~ 10% and the adjuvant of 90% ~ 99.9%.The ophthalmic preparation steady quality of the present invention, preparation technology is simple and convenient, and has carried out pharmacodynamic evaluation.
Description
Technical field
The present invention relates to a kind of for preventing and treating cataractous ophthalmic preparation and preparation method thereof.
Background technology
Crystalline lens metabolism disorder can be caused, cause crystallins degeneration that muddiness occurs, referred to as cataract.Most white
Cataract is Senile disease, but also has child innately to suffer from this disease, somebody injured, inflammation or sick after cataract occurs.
According to World Health Organization's incomplete statistics, whole world cataract blind person there are about 1600～21,000,000 people.Cataract one
As the course of disease slow, be that in ophthalmic diseases, sickness rate is the highest, be also the most dangerous, in treatment not in time or the feelings that do not note prevention
It is easy under condition eyes cause damage the most blind.
Cataractous treatment includes two aspects, and one is Drug therapy, and two is operative treatment.Early stage and cataract in mid-term are suffered from
Person can pass through Drug therapy, but there is no the probability cured completely at present, often waits until the period of maturation, crystalline by surgical removal muddiness
Body recovers vision, but due to the structural deterioration of postoperative crystalline lens self, and make the regulating power of himself lose, and also exist
The probability of multiple complications occurs, and the protective agents therefore seeking determined curative effect is the most important thing.
(3 β)-8,24-lanostadiene-3-alcohol, is commonly called as lanosterol, is in lanoline alkane type tetracyclic triterpenoid
One, English entitled lanosterol, No. CAS is 79-63-0, chemistry entitled 3 β-Hydroxy-8,24-
Lanostadiene, it has recently been found that use medicament for the eyes containing lanosterol 6 weeks to suffering from cataractous Canis familiaris L., it is possible to decrease cataractous sternly
Weight degree, improves lenticular transparency, lanosterol is described or has the compound of shares activity molecule, can be that treatment is white
Cataract provides another kind for the treatment of means, but the ophthalmic preparation relevant to lanosterol has no report.
Summary of the invention
The technical problem to be solved be to provide one effectively prevent and treat cataractous ophthalmic preparation and
Preparation method.
In order to solve above-mentioned technical problem, the present invention adopts the following technical scheme that
One is used for preventing and treating cataractous ophthalmic preparation, by weight percentage, its by 0.1%～10% sheep
Hair fat alkane type tetracyclic triterpenoid and the adjuvant composition of 90%～99.9%.
Preferably, the accounting of described lanoline alkane type tetracyclic triterpenoid is 0.1%～5%, more elects as
0.1%～2%.
Preferably, described lanoline alkane type tetracyclic triterpenoid is lanosterol.
Preferably, described adjuvant is selected from surfactant, isoosmotic adjusting agent, preservative, antioxidant, substrate, pH
One or more in regulator, penetrating agent, excipient, stabilizer, organic solvent, water.
Wherein, surfactant is also called solubilizing agent.
It is further preferred that described surfactant is selected from pegoxol 7 stearate, diethylene glycol mono-ethyl
Ether, Labraso, polyoxyethylene stearate (40) ester, polyoxyethylene (35) Oleum Ricini, Polyethylene Glycol 40 hydrogen
Change in Oleum Ricini, lecithin, tween 80, ethanol, Polyethylene Glycol, carbomer, poloxamer and HP-β-CD
Kind or several combinations.
In the present invention, the addition of described surfactant account for described ophthalmic preparation gross mass 0.05%～
25%, preferably 0.1%～10%, most preferably 0.1%～5%.
It is further preferred that described isoosmotic adjusting agent be selected from sodium chloride, potassium chloride, glucose, mannitol, the third two
The combination of one or more in alcohol, glycerol, boric acid, Borax.
In the present invention, the addition of described isoosmotic adjusting agent account for described ophthalmic preparation gross mass 0.05%～
25%, preferably 1%～15%, most preferably 5%～12%.
It is further preferred that described preservative is selected from triethanolamine, boric acid, Borax, sodium citrate, Metagin
Ester, ethyl hydroxybenzoate, propylparaben, ethyl hydroxybenzoate, phenylmercuric nitrate, benzalkonium chloride solution, ethyl hydroxybenzoate, benzene prick chlorine
The combination of one or more in ammonium, benzalkonium bromide, chlorhexidine acetate, polyquaternary ammonium salt, chlorobutanol, phenethanol, thimerosal.
In the present invention, the addition of described preservative accounts for the 0.0001%～1% of described ophthalmic preparation gross mass, excellent
Elect 0.0001%～0.1% as, most preferably 0.0001%～0.02%.
It is further preferred that described antioxidant is selected from sodium thiosulfate, sodium pyrosulfite, sodium sulfite, Asia
Sodium sulfate, disodium edetate, butylated hydroxyanisole, butylated hydroxytoluene, alpha-tocopherol, cyclohexanediamine four sodium acetate, N-hydroxy-ethylenediamine three
In acetic acid, diethyl triamine six acetic acid, two mercapto ethyl glycines and ethylenediaminetetraacetic acid, arabo-ascorbic acid and sodium salt thereof, thiourea
The combination of one or more.
In the present invention, the addition of described antioxidant accounts for the 0.0001%～1% of described ophthalmic preparation gross mass,
It is preferably 0.001%～0.1%, most preferably 0.01%～0.02%.
It is further preferred that described substrate is selected from Yellow Vaselin, white vaseline, lanoline, liquid paraffin, hyalomitome
Acid sodium, polyvinyl alcohol, carbomer, xanthan gum, chitosan, xylan, polyacrylic acid, sodium alginate, methylcellulose, hydroxypropyl first
The combination of one or more in cellulose, polyvidone.
In the present invention, the addition of described substrate accounts for the 0.5%～90% of described ophthalmic preparation gross mass, is preferably
1%～85%.
It is further preferred that described pH adjusting agent is selected from sodium hydroxide, hydrochloric acid, sodium acetate, sodium carbonate, bicarbonate
The combination of one or more in sodium, disodium hydrogen phosphate, sodium dihydrogen phosphate, boric acid, citric acid, sodium citrate.
In the present invention, the addition of described pH adjusting agent accounts for the 0～15% of described ophthalmic preparation gross mass.
It is further preferred that described penetrating agent is selected from lecithin, hyaluronate sodium, sodium lauryl sulphate, N-first
Base ketopyrrolidine, sodium deoxycholate, hydroxypropyl-cyclodextrin, laurocapram, disodiumedetate, tween 80, the third two
The combination of one or more in alcohol.
In the present invention, the addition of described penetrating agent accounts for the 0%～20% of described ophthalmic preparation gross mass, is preferably
0.05%～20%, most preferably 0.1%～0.5%.
Preferably, described stabilizer is cholesterol, soybean phospholipid, lecithin, glyceryl monooleate, tristearin, polyethylene
The combination of one or more in alcohol, Polyethylene Glycol, hypromellose, polyvinylpyrrolidone, poloxamer.
In the present invention, the addition of described stabilizer accounts for the 0%～90% of described ophthalmic preparation gross mass, is preferably
0.05%～10%, most preferably 1%～5%.
Preferably, described excipient is mannitol, dextran, lactose, galactose, chitosan, arginine, Portugal's first
Amine, cyclodextrin, gelatin, glucose, inositol, sucrose, trehalose, sorbitol, xylitol, albumin, peptone, solubility are formed sediment
The combination of one or more in powder, dextrin, arabic gum, hydroxymethyl cellulose, syrup.
In the present invention, the addition of described excipient accounts for the 0%～95% of described ophthalmic preparation gross mass, is preferably
0.1%～20%, most preferably 1%～10%.
Preferably, described organic solvent is the one in chloroform, ethanol, acetone, dimethyl sulfoxide, ethyl acrylate or several
The combination planted.
Preferably, described water is water for injection.
Preferably, described ophthalmic preparation is eye drop, eye ointment, gel for eye use, ophthalmically acceptable freeze-dried instant sheet or ophthalmically acceptable nanometer
Liposome.
Preferably, by weight percentage, described ophthalmic preparation includes following component:
It is further preferred that by weight percentage, described ophthalmic preparation includes following component:
In the present invention, when described ophthalmic preparation is eye drop, by weight percentage, described ophthalmic preparation includes
Following component:
Being preferably, by weight percentage, described ophthalmic preparation includes following component:
Preferably, by weight percentage, described ophthalmic preparation includes following component:
In the present invention, when described ophthalmic preparation is eye ointment, by weight percentage, described ophthalmic preparation include as
Lower component:
Preferably, by weight percentage, described ophthalmic preparation includes following component:
It is further preferred that by weight percentage, described ophthalmic preparation includes following component:
In the present invention, when described ophthalmic preparation is gel for eye use, by weight percentage, described ophthalmic preparation bag
Include following component:
Being preferably, by weight percentage, described ophthalmic preparation includes following component:
More preferably, by weight percentage, described ophthalmic preparation includes following component:
Preferably, by weight percentage, described ophthalmic preparation includes following component:
In the present invention, when described ophthalmic preparation is ophthalmically acceptable freeze-dried instant sheet, described ophthalmic preparation includes lanoline
Alkane type tetracyclic triterpenoid and excipient, described lanoline alkane type tetracyclic triterpenoid and described excipient
Mass ratio is 1:9～30, preferably 1:9～20, most preferably 1:10～15.
By weight percentage, described ophthalmic preparation includes following component:
In the present invention, when described ophthalmic preparation is ophthalmically acceptable nanometer liposome, by weight percentage, described is ophthalmically acceptable
Preparation includes following component:
Preferably, by weight percentage, described ophthalmic preparation includes following component:
It is further preferred that by weight percentage, described ophthalmic preparation includes following component:
It is a further object to provide a kind of described system for preventing and treat cataractous ophthalmic preparation
Preparation Method, obtains described ophthalmically acceptable system by described lanoline alkane type tetracyclic triterpenoid and described adjuvant mix homogeneously
Agent.
In the present invention, when described ophthalmic preparation is eye drop, this preparation method is: by described lanoline alkane type four
Ring triterpenoid compound and described surfactant are mixed to form the first mixture, described preservative and described water are mixed
Close and form the second mixture, after the first described mixture and the second described mixture stirring and dissolving, through pressure sterilizing
Obtain described eye drop.
Preferably, the temperature of described pressure sterilizing is 100～130 DEG C, and the time is 20～40min.
In the present invention, when described ophthalmic preparation is eye ointment, this preparation method is: by described lanoline alkane type Fourth Ring
Antioxidant described in triterpenoid compound, described substrate, described isoosmotic adjusting agent, part adds heat fusing and forms oil phase,
By described surfactant, remaining described antioxidant, described preservative and the water heating for dissolving shape described in part
Become mixed liquor, then described mixed liquor is added described in oil phase in, add remaining described water, mix homogeneously and get final product
Described eye ointment.
Preferably, the temperature adding heat fusing is 70～80 DEG C；The temperature of heating for dissolving is 70～80 DEG C.
In the present invention, when described ophthalmic preparation is gel, this preparation method is: described by adding in described substrate
Water to carry out moistening swelling, be subsequently adding described preservative, stirring and dissolving forms the first mixed liquor, by described lanoline alkane
Type tetracyclic triterpenoid and described surfactant are mixed to form the second mixed liquor, then by the second described mixed liquor
In the first mixed liquor described in addition, mix homogeneously i.e. obtains described gel.
In the present invention, when described ophthalmic preparation is freeze-dried instant sheet, this preparation method is: by molten for described excipient
In water described in Xie Yu, being subsequently adding described lanoline alkane type tetracyclic triterpenoid, the postlyophilization that is uniformly dispersed is i.e.
Freeze-dried instant sheet described in.
In the present invention, when described ophthalmic preparation is nanometer liposome, this preparation method is: by described lanoline alkane
Type tetracyclic triterpenoid, described stabilizer are scattered in described organic solvent and form the first mixed liquor, by described
Substrate, described penetrating agent are scattered in the water described in part, form the second mixed liquor, are scattered in by the first described mixed liquor
In the second described mixed liquor, form the 3rd mixed liquor, by the 3rd described mixed liquor vacuum rotary steam, obtain nanocrystal suspendible
Liquid, to the antioxidant described in described nanocrystal suspension addition, described preservative, remaining described water, mixing
Uniformly i.e. obtain described nanometer liposome.
Owing to using above technical scheme, the present invention compared with prior art has the advantage that
The ophthalmic preparation of the present invention has good curative effect, and the ophthalmic preparation of the present invention to cataractous prevention and treatment
Steady quality, prepares simple and convenient.
Figure of description
Fig. 1 is lenticular opacity grading schematic diagram (Hiraoka T, 1995).
Detailed description of the invention
Below in conjunction with specific embodiment, technical scheme is further described, but the present invention should not necessarily be limited by this
A little embodiments.
Embodiment 1 to 5, comparative example 1: the composition of raw materials of lanosterol eye drop sees table 1, preparation method is: weigh sheep
Hair sterol adds in surfactant, stirring so that it is fully inclusion.Weigh preservative to be dissolved in water for injection.By preservative
Aqueous solution adds in lanosterol mixture, stirring and dissolving.Pressure sterilizing, 115 DEG C, 30min.
Table 1
Embodiment 6 to 10, comparative example 2: the composition of raw materials of lanosterol eye ointment sees table 2, preparation method is: weigh Pilus Caprae seu Ovis
Melt in sterol, substrate, isoosmotic adjusting agent, Partial Antioxidation agent water-bath, be heated to 75 DEG C.Separately weigh surfactant, residue
Antioxidant, preservative are dissolved in partial syringe water, are heated to 75 DEG C.It is slowly added in oil phase, stirring while adding, add residue
Water for injection, mix homogeneously.
Table 2
Embodiment 11 to 15, comparative example 3: the composition of raw materials of lanosterol gel sees table 3, preparation method is: by substrate
Add moistening in water for injection swelling, add preservative, stirring and dissolving.Lanosterol is added in surfactant stir molten
Solve.Then lanosterol solution is slowly added in matrix solution, is uniformly mixed.
Table 3
Embodiment 16 to 20, comparative example 4: the composition of raw materials of lanosterol ophthalmically acceptable freeze-dried instant sheet sees table 4, preparation method
For: excipient adding stirring and dissolving in water for injection, adds lanosterol and be uniformly dispersed, fill is in ready bubble-cap
In, lyophilization and obtain.
Equipped with buffer in another 5ml eye-drop liquid bottle.Outward winding during use the big bottle cap of eye-drop liquid bottle, with thumb, tablet is extruded
Put in bottle, screw bottle cap shaking.
Table 4
Embodiment 21 to 25, comparative example 5: the composition of raw materials of lanosterol nanometer liposome sees table 5, preparation method is:
By lanosterol, stabilizer, it is scattered in organic solvent, obtains solution 1.Substrate, the swelling partial syringe that is scattered in of penetrating agent are used
In water, obtain solution 2.By solution 1 high speed shear or ultrasonic disperse in solution 2, obtain solution 3.By solution 3 vacuum rotary steam, must receive
Rice crystallization suspension, for solution 4.Antioxidant, preservative, residue water for injection, mix homogeneously is added in solution 4.
Table 5
Cataractous therapeutical effect is studied by embodiment 1 to 25, the ophthalmic preparation of comparative example 1 to 5
SD rat, in the sodium selenite solution of children's Mus neck dorsal sc injection 2mmol/L concentration, injection dosage is 25 μ
mol/kg。
After modeling 4 days (D5), under slit lamp, check lenticular opacity degree and take a picture, by Hiraoka T staging pair
Lenticular opacity degree carries out classification, is divided into 7 grades, refers to table 6.Slit lamp photography takes a full eye under normotopia diffused light of opening one's eyes and shines
Sheet and one is opened one's eyes under the slit of illumination of position, side (on the right side of slit of illumination 40 °, slit of illumination width 2mm) photo, refers to Fig. 1.
Table 6
Selecting 8 before animal modeling at random and be left intact as Normal group, D5 selects crystalline substance in modeling animal
The animal of shape body turbidity 1～3 grades enters group, is grouped according to lenticular opacity degree, it is ensured that when packet, crystalline lens mixes
Turbid degree is without significant difference.It is respectively model control group, the experimental group of embodiment 1 to 25, the contrast groups of comparative example 1 to 5 and sun
Property matched group, often group 8.
Model control group gives solvent.
Experimental group and contrast groups, the eye drop during eye drip gives embodiment 1 to 25, comparative example 1 to 5 respectively, dosage
For 0.015mg/ eye.
Positive controls, eye drip gives phacolin 0.00225mg/ eye.
Each administration group is given daily 4 times, successive administration 6 weeks (D5～D47).
Administration capacity: 15 μ l/ eyes/time, eyes are administered.
Investigating the general clinical observation of content (1), during test, every day observes all animals once, observe dead, fall ill, exhale
Suction, secretions, feces and diet, drinking-water situation etc..Observed through 47 days and find that all animals are showed no exception.
(2) respectively at D5, D7, D12, D19, D26, D33, D40, D47, lenticular opacity degree is carried out classification, and to crystalline substance
Shape body muddiness speckle carries out diameter measurement, records every animal eyes lenticular opacity speckle diameter.Each treated animal is interior in vain
Barrier number of cases is summed up and is referred to table 7, and lenticular opacity speckle average diameter is summed up and referred to table 8.
Table 7
Table 8
When evaluating the generation change of medicine Physiology and biochemistry lenticular to cataract, selenite induced catatract model is most-often used
Animal model, the feature of this model, application and relation cataractous with the mankind thereof have been summarized.Lanosterol ophthalmic preparation pair
The progress of 1 grade and 2 grades SD rat selenite induced catatract has certain retarding action, and meaning can control cataractous progress, to 3 grades
Cataract has certain rehabilitation and therapeutical effect.Lanosterol ophthalmic preparation and commercially available phacolin eye drop are carried out pharmacodynamics
Contrast, result of the test shows, on the most cataractous therapeutic effect, lanosterol eye drop is significantly better than phacolin eye drip
Liquid.
Claims (10)
1. one kind is used for preventing and treat cataractous ophthalmic preparation, it is characterised in that: by weight percentage, its by 0.1% ~
The lanoline alkane type tetracyclic triterpenoid of 10% and the adjuvant composition of 90% ~ 99.9%.
It is the most according to claim 1 for preventing and treating cataractous ophthalmic preparation, it is characterised in that: described Pilus Caprae seu Ovis
Fat alkane type tetracyclic triterpenoid is lanosterol.
It is the most according to claim 1 for preventing and treating cataractous ophthalmic preparation, it is characterised in that: described adjuvant
For selected from surfactant, isoosmotic adjusting agent, preservative, antioxidant, substrate, pH adjusting agent, penetrating agent, excipient, stable
One or more in agent, organic solvent, water.
It is the most according to claim 3 for preventing and treating cataractous ophthalmic preparation, it is characterised in that: described surface
Activating agent is selected from pegoxol 7 stearate, TC, Labraso, tristearin
Poly-hydrocarbon oxygen (40) ester of acid, polyoxyethylene (35) Oleum Ricini, Polyethylene Glycol 40 castor oil hydrogenated, lecithin, tween 80, ethanol, poly-
The combination of one or more in ethylene glycol, carbomer, poloxamer and HP-β-CD；
Described isoosmotic adjusting agent is selected from sodium chloride, potassium chloride, glucose, mannitol, propylene glycol, glycerol, boric acid, Borax
In the combination of one or more；
Described preservative is selected from triethanolamine, boric acid, Borax, sodium citrate, methyl hydroxybenzoate, ethyl hydroxybenzoate, Ni Bo
Gold propyl ester, ethyl hydroxybenzoate, phenylmercuric nitrate, benzalkonium chloride solution, ethyl hydroxybenzoate, benzalkonium chloride, benzalkonium bromide, acetic acid chlorine are own
Calmly, the combination of one or more in polyquaternary ammonium salt, chlorobutanol, phenethanol, thimerosal；
Described antioxidant be selected from sodium thiosulfate, sodium pyrosulfite, sodium sulfite, sodium sulfite, disodium edetate,
Butylated hydroxyanisole, butylated hydroxytoluene, alpha-tocopherol, cyclohexanediamine four sodium acetate, N-hydroxy-ethylenediamine three acetic acid, diethyl triamine six vinegar
The combination of one or more in acid, two mercapto ethyl glycines and ethylenediaminetetraacetic acid, arabo-ascorbic acid and sodium salt thereof, thiourea；
Described substrate is selected from Yellow Vaselin, white vaseline, lanoline, liquid paraffin, hyaluronate sodium, polyvinyl alcohol, card
In ripple nurse, xanthan gum, chitosan, xylan, polyacrylic acid, sodium alginate, methylcellulose, hypromellose, polyvidone
The combination of one or more；
Described pH adjusting agent is selected from sodium hydroxide, hydrochloric acid, sodium acetate, sodium carbonate, sodium bicarbonate, disodium hydrogen phosphate, phosphoric acid
The combination of one or more in sodium dihydrogen, boric acid, citric acid, sodium citrate；
Described penetrating agent is selected from lecithin, hyaluronate sodium, sodium lauryl sulphate, N-Methyl pyrrolidone, deoxidation gallbladder
One or more in acid sodium, hydroxypropyl-cyclodextrin, laurocapram, disodiumedetate, tween 80, propylene glycol
Combination；
Described stabilizer be cholesterol, soybean phospholipid, lecithin, glyceryl monooleate, tristearin, polyvinyl alcohol, Polyethylene Glycol,
The combination of one or more in hypromellose, polyvinylpyrrolidone, poloxamer；
Described excipient is mannitol, dextran, lactose, galactose, chitosan, arginine, meglumine, cyclodextrin, bright
Glue, glucose, inositol, sucrose, trehalose, sorbitol, xylitol, albumin, peptone, soluble starch, dextrin, Arab
The combination of one or more in glue, hydroxymethyl cellulose, syrup；
Described organic solvent is the combination of one or more in chloroform, ethanol, acetone, dimethyl sulfoxide, ethyl acrylate；
Described water is water for injection.
It is the most according to claim 1 for preventing and treating cataractous ophthalmic preparation, it is characterised in that: described is ophthalmically acceptable
Preparation is eye drop, eye ointment, gel for eye use, ophthalmically acceptable freeze-dried instant sheet or ophthalmically acceptable nanometer liposome.
The most according to any one of claim 1 to 5 for preventing and treating cataractous ophthalmic preparation, its feature exists
In: by weight percentage, described ophthalmic preparation includes following component:
Lanoline alkane type tetracyclic triterpenoid 0.1% ~ 10%；
Surfactant 0.05% ~ 25%；
Preservative 0.00001% ~ 0.5%；
Water 65% ~ 99%.
The most according to any one of claim 1 to 5 for preventing and treating cataractous ophthalmic preparation, its feature exists
In: by weight percentage, described ophthalmic preparation includes following component:
Lanoline alkane type tetracyclic triterpenoid 0.1% ~ 10%；
Substrate 0.5% ~ 90%；
Surfactant 0.05% ~ 25%；
Isoosmotic adjusting agent 0.5% ~ 15%；
Preservative 0.001% ~ 0.5%；
Antioxidant 0.001% ~ 0.5%；
Water 3% ~ 98%.
The most according to any one of claim 1 to 5 for preventing and treating cataractous ophthalmic preparation, its feature exists
In: by weight percentage, described ophthalmic preparation includes following component:
Lanoline alkane type tetracyclic triterpenoid 0.1% ~ 10%；
Substrate 0.1 ~ 10%；
Surfactant 0.05% ~ 25%；
Preservative 0.00001% ~ 0.5%；
Water 65% ~ 99%.
The most according to any one of claim 1 to 5 for preventing and treating cataractous ophthalmic preparation, its feature exists
In: described ophthalmic preparation includes lanoline alkane type tetracyclic triterpenoid and excipient, described lanoline alkane type Fourth Ring
The mass ratio of triterpenoid compound and described excipient is 1:9 ~ 30.
The most according to any one of claim 1 to 5 for preventing and treating cataractous ophthalmic preparation, its feature exists
In: by weight percentage, described ophthalmic preparation includes following component:
Lanoline alkane type tetracyclic triterpenoid 0.1% ~ 10%；
Substrate 0.1% ~ 90%；
Preservative 0.001% ~ 0.5%；
Antioxidant 0.001% ~ 0.5%；
Penetrating agent 0.05% ~ 20%；
Stabilizer 0.5% ~ 90%；
Organic solvent 0.1% ~ 15%
Water 3% ~ 98%.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811324473.1A CN109364019B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324188.XA CN109481450B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324475.0A CN109364020B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324187.5A CN109481392B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510552362 | 2015-09-02 | ||
| CN2015105523626 | 2015-09-02 |
Related Child Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811324473.1A Division CN109364019B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324187.5A Division CN109481392B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324188.XA Division CN109481450B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324475.0A Division CN109364020B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106074568A true CN106074568A (en) | 2016-11-09 |
| CN106074568B CN106074568B (en) | 2021-05-14 |
Family
ID=58069868
Family Applications (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811324473.1A Active CN109364019B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324475.0A Active CN109364020B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201610696992.5A Active CN106074568B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324188.XA Active CN109481450B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324187.5A Active CN109481392B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811324473.1A Active CN109364019B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324475.0A Active CN109364020B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811324188.XA Active CN109481450B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
| CN201811324187.5A Active CN109481392B (en) | 2015-09-02 | 2016-08-22 | Ophthalmic preparation for preventing and treating cataract and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (5) | CN109364019B (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344587A (en) * | 2016-08-24 | 2017-01-25 | 上海毕傲图生物科技有限公司 | Lanosterol compound preparation for eyes |
| WO2018137683A1 (en) * | 2017-01-25 | 2018-08-02 | 中山大学中山眼科中心 | Lanosterol prodrug compound and preparation method therefor and use thereof |
| CN108524448A (en) * | 2017-03-02 | 2018-09-14 | 新疆维吾尔自治区药物研究所 | A kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application |
| JP2019048799A (en) * | 2017-09-08 | 2019-03-28 | ライオン株式会社 | Ophthalmologic composition and tear fluid oil layer stabilizer |
| CN109820825A (en) * | 2017-11-23 | 2019-05-31 | 河北嘉硕生物科技有限公司 | It is a kind of for treating the pharmaceutical composition of eye disease |
| CN109985052A (en) * | 2017-12-29 | 2019-07-09 | 上海蓝木化工有限公司 | The new application of triterpene compound |
| CN110404057A (en) * | 2019-07-09 | 2019-11-05 | 武汉华肽生物科技有限公司 | A kind of pharmaceutical composition and its application based on gene recombinant protein Tat-hMsrA |
| WO2020129964A1 (en) * | 2018-12-18 | 2020-06-25 | 参天製薬株式会社 | Ursodeoxycholic acid-containing agent for treating or preventing presbyopia |
| WO2020177714A1 (en) * | 2019-03-04 | 2020-09-10 | 中山大学中山眼科中心 | Composition of lanosterol prodrug compound, preparation method therefor and use thereof |
| CN112336870A (en) * | 2020-12-03 | 2021-02-09 | 温州医科大学 | Sustained-release system with synergistic effect of various vitamins in eyes and preparation method thereof |
| CN113413415A (en) * | 2021-06-30 | 2021-09-21 | 东莞博盛生物科技有限公司 | Lanosterol eye drops and preparation method thereof |
| WO2023030430A1 (en) * | 2021-09-03 | 2023-03-09 | 成都瑞沐生物医药科技有限公司 | Ophthalmic formulation for preventing and/or treating cataracts by eye drop administration |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102112133A (en) * | 2008-08-05 | 2011-06-29 | 阿马佐尼亚菲托药品有限公司 | Pharmaceutical uses of lanosta-8, 24-dien-3-ols |
| WO2016029199A1 (en) * | 2014-08-22 | 2016-02-25 | Kang Zhang | Compositions and methods to treat vision disorders |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA837050A (en) * | 1970-03-17 | L. Bouthelier Jean | Method of and composition for the treatment of human carcinoma and hypercholestrolemia | |
| EP0785212A1 (en) * | 1996-01-22 | 1997-07-23 | Laboratoire Theramex | New 19-nor-pregnene derivatives |
| KR20080059336A (en) * | 2005-05-17 | 2008-06-26 | 모리나가 뉴교 가부시키가이샤 | Food or drink for improving pancreatic functions |
| EP2255788B1 (en) * | 2008-02-29 | 2015-07-22 | Nagoya Industrial Science Research Institute | Liposome for delivery to posterior segment of eye and pharmaceutical composition for disease in posterior segment of eye |
| GB201101669D0 (en) * | 2011-01-31 | 2011-03-16 | Ip Science Ltd | Carotenoid particles and uses thereof |
| US20140271884A1 (en) * | 2011-10-25 | 2014-09-18 | The Trustees Of Princeton University | High-loading nanoparticle-based formulation for water-insoluble steroids |
| CN104352361B (en) * | 2014-11-20 | 2017-05-24 | 广州神采化妆品有限公司 | Variable-colour transparent lipstick and preparation method thereof |
-
2016
- 2016-08-22 CN CN201811324473.1A patent/CN109364019B/en active Active
- 2016-08-22 CN CN201811324475.0A patent/CN109364020B/en active Active
- 2016-08-22 CN CN201610696992.5A patent/CN106074568B/en active Active
- 2016-08-22 CN CN201811324188.XA patent/CN109481450B/en active Active
- 2016-08-22 CN CN201811324187.5A patent/CN109481392B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102112133A (en) * | 2008-08-05 | 2011-06-29 | 阿马佐尼亚菲托药品有限公司 | Pharmaceutical uses of lanosta-8, 24-dien-3-ols |
| WO2016029199A1 (en) * | 2014-08-22 | 2016-02-25 | Kang Zhang | Compositions and methods to treat vision disorders |
| CN107206009A (en) * | 2014-08-22 | 2017-09-26 | 广州康睿生物医药科技股份有限公司 | Composition and method for treating dysopia |
Non-Patent Citations (1)
| Title |
|---|
| LING ZHAO ET AL.: ""Lanosterol reverses protein aggregation in cataracts"", 《NATURE》 * |
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106344587A (en) * | 2016-08-24 | 2017-01-25 | 上海毕傲图生物科技有限公司 | Lanosterol compound preparation for eyes |
| US10738076B2 (en) | 2017-01-25 | 2020-08-11 | Zhongshan Ophthalmic Center, Sun Yat-Sen University | Lanosterol prodrug compound and preparation method therefor and use thereof |
| WO2018137683A1 (en) * | 2017-01-25 | 2018-08-02 | 中山大学中山眼科中心 | Lanosterol prodrug compound and preparation method therefor and use thereof |
| CN109415406A (en) * | 2017-01-25 | 2019-03-01 | 中山大学中山眼科中心 | Lanosterol prodrug compound and its preparation method and application |
| CN108524448A (en) * | 2017-03-02 | 2018-09-14 | 新疆维吾尔自治区药物研究所 | A kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application |
| JP2019048799A (en) * | 2017-09-08 | 2019-03-28 | ライオン株式会社 | Ophthalmologic composition and tear fluid oil layer stabilizer |
| JP7056480B2 (en) | 2017-09-08 | 2022-04-19 | ライオン株式会社 | Ophthalmic composition and tear oil layer stabilizer |
| CN109820825A (en) * | 2017-11-23 | 2019-05-31 | 河北嘉硕生物科技有限公司 | It is a kind of for treating the pharmaceutical composition of eye disease |
| CN109985052A (en) * | 2017-12-29 | 2019-07-09 | 上海蓝木化工有限公司 | The new application of triterpene compound |
| WO2020129964A1 (en) * | 2018-12-18 | 2020-06-25 | 参天製薬株式会社 | Ursodeoxycholic acid-containing agent for treating or preventing presbyopia |
| JP6771698B1 (en) * | 2018-12-18 | 2020-10-21 | 参天製薬株式会社 | Presbyopia treatment or prophylaxis containing ursodeoxycholic acid |
| US11419880B2 (en) | 2018-12-18 | 2022-08-23 | Santen Pharmaceutical Co., Ltd. | Ursodeoxycholic acid-containing agent for treating or preventing presbyopia |
| WO2020177714A1 (en) * | 2019-03-04 | 2020-09-10 | 中山大学中山眼科中心 | Composition of lanosterol prodrug compound, preparation method therefor and use thereof |
| CN110404057A (en) * | 2019-07-09 | 2019-11-05 | 武汉华肽生物科技有限公司 | A kind of pharmaceutical composition and its application based on gene recombinant protein Tat-hMsrA |
| CN112336870A (en) * | 2020-12-03 | 2021-02-09 | 温州医科大学 | Sustained-release system with synergistic effect of various vitamins in eyes and preparation method thereof |
| CN113413415A (en) * | 2021-06-30 | 2021-09-21 | 东莞博盛生物科技有限公司 | Lanosterol eye drops and preparation method thereof |
| CN113413415B (en) * | 2021-06-30 | 2022-09-27 | 东莞博盛生物科技有限公司 | Lanosterol eye drops and preparation method thereof |
| WO2023030430A1 (en) * | 2021-09-03 | 2023-03-09 | 成都瑞沐生物医药科技有限公司 | Ophthalmic formulation for preventing and/or treating cataracts by eye drop administration |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109481392B (en) | 2021-12-24 |
| CN109364019B (en) | 2021-12-28 |
| CN109481450B (en) | 2021-07-23 |
| CN106074568B (en) | 2021-05-14 |
| CN109364019A (en) | 2019-02-22 |
| CN109481450A (en) | 2019-03-19 |
| CN109364020A (en) | 2019-02-22 |
| CN109481392A (en) | 2019-03-19 |
| CN109364020B (en) | 2021-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106074568A (en) | One is used for preventing and treat cataractous ophthalmic preparation and preparation method thereof | |
| CN1197550C (en) | Composition set and kit for use in intraocular surgery | |
| BRPI0720434A2 (en) | USEFUL GEL FOR OPHTHALMIC PHARMACEUTICAL RELEASE | |
| KR102382077B1 (en) | Composition for prevention or treatment of visual disorders comprising ursodeoxycholic acid | |
| CN114129575A (en) | Preparation method and application of pharmaceutical composition | |
| CN112426405A (en) | Pharmaceutical composition for preventing and controlling myopia development, eye drops and preparation method and application thereof | |
| CA2903114A1 (en) | Ophthalmic formulations | |
| CN112402371B (en) | Rudesiwei injection and preparation method thereof | |
| CN111494305A (en) | Lutein liposome ophthalmic temperature-sensitive in-situ gel preparation and preparation method thereof | |
| CN105943500A (en) | Isavuconazole-containing nano-micelle antifungal solution for eyes | |
| CN111450054B (en) | Ophthalmic preparation containing caffeic acid ester, preparation method and application | |
| CN113786380A (en) | Pilocarpine nitrate ophthalmic gel and preparation method thereof | |
| CN104546828B (en) | Application of the butylphthalide or derivatives thereof in the medicine for treating or preventing diabetic complication is prepared | |
| CN112957481A (en) | Insoluble drug inclusion compound, inclusion method and chlortetracycline hydrochloride soluble powder | |
| CN105935443A (en) | Pharmaceutical composition for treating diabetic cataract | |
| CN108524448B (en) | A kind of euphadienol anti-cataract eye-drops preparations and its preparation method and application | |
| CN115212200B (en) | Puerarin-containing compound preparation for treating diabetic complications and preparation method thereof | |
| CN107970205A (en) | Disulfiram instant-type gel eye drops and its preparation and application | |
| CN110876746B (en) | Ginkgo diterpene lactone eye preparation and preparation method and application thereof | |
| EP4225279A1 (en) | Drug containing dissolvable ocular inserts and method of using same | |
| RU2071772C1 (en) | Medicinal agent for multiple sclerosis treatment | |
| CN109646438A (en) | The application of demethyl coclaurine or its hydrochloride in preparation treatment rhinitis drug | |
| CN112641722A (en) | Injection and preparation process thereof | |
| CN114831935A (en) | Sterile 20(S) -PPD oral liquid preparation capable of being administrated by nasal feeding and preparation method and application thereof | |
| CN112190544A (en) | Levetiracetam composition, preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address |
Address after: 215123 units 101 and 102, C11 building, phase I project of biomedical industrial park, No. 218 Xinghu street, Suzhou Industrial Park, China (Jiangsu) pilot Free Trade Zone, Suzhou, Jiangsu Province Patentee after: Shengshi Taike Biopharmaceutical Technology (Suzhou) Co.,Ltd. Address before: 215123 Room 101, C11 / F, bio nano Park, 218 Xinghu street, Suzhou Industrial Park, Suzhou City, Jiangsu Province Patentee before: CGENE TECH (SUZHOU, CHINA) Co.,Ltd. |
|
| CP03 | Change of name, title or address |