CN107456440A - A kind of low concentration atropic category medicament dropping ocular fluid and preparation method thereof - Google Patents
A kind of low concentration atropic category medicament dropping ocular fluid and preparation method thereof Download PDFInfo
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Abstract
A kind of low concentration atropic category medicament dropping ocular fluid, it is made up of following each component：(A) atropic category medicine, 0.001%~1% (w/v)；(B) there is the solute of lubrication, solubilising and moisture-keeping function, 0%~10% (w/v)；(C) acid-base modifier, its amount is adjusted to 6.0~8.0 by pH to be defined；(D) osmotic buffering agent, its amount is adjusted to 280~380mOsm/L by osmotic pressure to be defined；(E) thickener, its amount is adjusted to 6~10mps by viscosity to be defined；(F) have and stablize the pharmaceutically-active solute of atropic category, 0.001%~1% (w/v)；(G) bacteriostatic agent, 0%~0.1% (w/v)；Ensureing safety and on the premise of not influenceing main ingredient effect, also can be optionally added peppermint, natural borneol, vitamin B6, dipotassium glycyrrhizinate or other there is one or more in booster action material, 0%~0.1% (w/v)；Surplus is water.The eye drops of the present invention, main ingredient stability is good, safety, is not easy microbial contamination, effectively can prevent and delay adolescent myopia.
Description
Technical field
The present invention relates to a kind of atropic category medicament dropping ocular fluid, in particular to a kind of low concentration atropic category medicine
Eye drops and preparation method thereof.
Background technology
Eyes are one of most important organs of the mankind, and adapting to social life for people provides guarantee.As people live
Horizontal raising and the quickening of rhythm of life, each electronic product have turned into the necessity of life, people more and more according to
Rely the video display terminal such as computer, TV to carry out various activities, people with having more several times than over the past several decades between at the moment, allow eye
The time that eyeball is rested is fewer and fewer.For teenager and children, with the development of the society, learning tasks day
Gradually heavy, few extracurricular activities time, and the time learn, read, writing etc. is increasingly longer, work for a long time or
It is wrongful excessively to use eyes, novel is such as seen, electronic game is played, sees that TV etc. makes ciliary muscle contracts last, in spasm shape
State, the time, which has been grown, will occur myopia.
At present, the incidence of China's myopia has been risen to the second for being only second to Japan, whole nation myopia by third place in the world
Eye number there are about 400,000,000, and near-sighted population incidence is 30~35%, be approximately 1.5 times of world average level.In recent years, China is near
There is the trend sharply increased depending on eye rate, and age of onset is small, the incidence of disease is high, and student is the main morbidity colony of myopia, China
Adolescent patient myopia quantity increases in geometry level, and wherein adolescent myopia has people more than 200,000,000, adolescents in China myopia incidence of disease height
Up to 50%~60%, newly-increased myopia is about 6% every year.The rate of myopia of Chinese student has been discharged to the second in the world, is only second to new add
Slope, the incidence of disease of its students in middle and primary schools is 30%~40%, and the incidence of disease of junior school student is 50%~60%, high school student is 70%~
80%, university student is then up to more than 90%.
In view of the present situation of youngsters and children myopia, and the whole world there is no active drug to treat myopia at present, so for
The prevention work of myopia is just particularly important.Research shows, atropic category medicament dropping ocular fluid can effectively delay child myopia, Ah
Tropine class drug concentration is higher, and retarding myopia progress effect is better.But high concentration atropic category medicament dropping ocular fluid, because it is secondary
Play a role clearly, it may appear that phenomena such as mydriasis effect is strong, photophobia, eye-blurred, easily cause patient's discomfort, and it is high
The atropic category medicament dropping ocular fluid of concentration may can also trigger some adverse events, such as be likely to occur allergic conjunctivitis, allergy
Property blear-eye the problems such as, long-term use of high concentration atropic category medicine can may also cause Retinal infringement, concurrency it is interior in vain
Such as more early there is at the illness in barrier, induction presbyopia.
The above situation can seldom occur for the atropic category medicament dropping ocular fluid of low concentration, even if occurring using atropic category once in a while
Situations such as cycloplegia, photophobia, nearly thing are fuzzy caused by medicine eye drops, can be restored quickly after drug withdrawal, and use
The atropic category medicament dropping ocular fluid recovery of high concentration is got up just relatively difficult.The ophthalmologist, oculist of Singapore passes through years of researches table
Bright, the atropic category medicament dropping ocular fluid of low concentration is the method for extraordinary prevention and retarding myopia for current.
But the atropic category medicament dropping ocular fluid of low concentration is being prepared, in production and prolonged storage, due to atropine
Contain ester bond in class drug molecule, it is unstable, if disposal options are improper, will by temperature, illumination, pH value of solution, storage when
Between the influence that waits, and occur in the solution rotten or even fail, produce corresponding alcohol or acid, these products are i.e. without clinic
Drug effect, and when patient is using rotten eye drops, may can also there is certain potential safety hazard and side effect.
Many eyedrops in the market, in order to keep aseptic and shelf-life, bacteriostatic agent and trace element are added, is had
Research finds, the long-term excessive contact bacteriostatic agent of human body eye, it is possible to can cause potential safety hazard to our eye, may such as lead
Normal tear film is caused to be destroyed, corneal epithelial cell damages, and damage ophthalmic retina etc., is damaged to eyes.Add
Some eyedrops purposes is explained not clear, is not inconsistent with symptom, and long-term use produces side effect, damages eyes, although now with without
Bacteriostatic agent, partly it is pure natural eyedrops, but it is few specifically for myopia, particularly adolescent myopia, for having
Effect alleviates the eyedrops of youngsters and children myopia.
Therefore, a kind of low concentration that can effectively prevent adolescent myopia, main ingredient stabilization, highly effective and safe and have no side effect is researched and developed
Atropine eyedrops is this area about research and development and medical worker's technical problem urgently to be resolved hurrily.In order to solve the above technical problems,
We have proposed a kind of low concentration atropic category medicament dropping ocular fluid of not bacteriostatic agent, it both effectively can prevent and delay teenager
Myopia, the side effects such as the infringement and stimulation to ocular tissue's cell such as bacteriostatic agent and hydrolysate can be avoided again, it is safe and stable, just
In long-term storage.More specifically, we are preparing with production process on the premise of drug safety is ensured, are passing through addition
Isotonic agent, pH, viscosity and the auxiliary material of increase drug solubility and preparation stability are adjusted to improve the stability of main ingredient, extends drop
The shelf-life of ocular fluid.
The content of the invention
The present invention provides a kind of low concentration atropic category medicament dropping ocular fluid, and it is made up of following each component：
(A) atropic category medicine, 0.001%~1% (w/v)；
(B) there is the solute of lubrication, solubilising and moisture-keeping function, 0%~10% (w/v)；
(C) acid-base modifier, its amount is adjusted to 6.0~8.0 by pH to be defined；
(D) osmotic buffering agent, its amount is adjusted to 280~380mOsm/L by osmotic pressure to be defined；
(E) thickener, its amount is adjusted to 6~10mps by viscosity to be defined；
(F) have and stablize the pharmaceutically-active solute of atropic category, 0.001%~1% (w/v)；
(G) bacteriostatic agent, 0%~0.1% (w/v)；
Also can be optionally added peppermint, natural borneol, vitamin B6, dipotassium glycyrrhizinate or other there is booster action material
In one or more, 0%~0.1% (w/v)；
Surplus is water.
The present invention also provides the preparation method of low concentration atropic category medicament dropping ocular fluid, and it comprises the following steps：
1. atropic category medicine is made into the aqueous solution that concentration is 0.001%~1% (w/v),
2. then adding 0%~10% (w/v) in resulting solution into step 1 has lubrication, solubilising and moisture-keeping function
Solute, and be well mixed,
3. then adding acid-base modifier into step 2 resulting solution, its pH is adjusted to 6.0~8.0,
4. adding osmotic buffering agent into step 3 resulting solution, its osmotic pressure is adjusted to 280~380mOsm/L,
5. adding thickener into step 4 resulting solution, its viscosity is adjusted to 6~10mps,
6:It is pharmaceutically-active with atropic category is stablized that 0.001%~1% (w/v) is added into step 5 resulting solution again
Solute,
7. finally by added in step 6 resulting solution 0%~0.1% (w/v) bacteriostatic agent and optional 0%~
0.1% (w/v) peppermint, natural borneol, vitamin B6, dipotassium glycyrrhizinate or other have one kind in booster action material or
Sterilized after a variety of and filling, produce low concentration atropic category medicament dropping ocular fluid finished product.
It is used for the purposes for preventing and delaying adolescent myopia present invention also offers low concentration atropic category medicament dropping ocular fluid.
Low concentration atropic category medicament dropping ocular fluid security of the invention is good, drug effect is high, main ingredient is stable, can effectively prevent
With delay adolescent myopia, the side effects such as infringement and stimulation of the bacteriostatic agent to ocular tissue's cell can be avoided again.
Embodiment
In the present invention, as without opposite explanation, then all operations in room temperature, normal pressure, keep away under intense light conditions and implement.
The low concentration atropic category medicament dropping ocular fluid of the present invention, it is made up of following each component：
(A) atropic category medicine, 0.001%~1% (w/v)；
(B) there is the solute of lubrication, solubilising and moisture-keeping function, 0%~10% (w/v)；
(C) acid-base modifier, its amount is adjusted to 6.0~8.0 by pH to be defined；
(D) osmotic buffering agent, its amount is adjusted to 280~380mOsm/L by osmotic pressure to be defined；
(E) thickener, its amount is adjusted to 6~10mps by viscosity to be defined；
(F) have and stablize the pharmaceutically-active solute of atropic category, 0.001%~1% (w/v)；
(G) bacteriostatic agent, 0%~0.1% (w/v)；
Also can be optionally added peppermint, natural borneol, vitamin B6, dipotassium glycyrrhizinate or other there is booster action material
In one or more, 0%~0.1% (w/v)；
Surplus is water.
In one embodiment of the invention, low concentration atropic category medicament dropping ocular fluid of the invention also optionally adds
Enter 0%~0.1% (w/v) one or more following additives：Peppermint or natural borneol, to provide refrigerant, pleasant sensation；
Vitamin B6, to improve local immunity；Dipotassium glycyrrhizinate, to provide anti-inflammatory, antianaphylactic effect, or other have booster action
The material of effect.
In one embodiment of the invention, the atropic category medicine can be atropine sulfate, sulfuric acid atropina,
Sulfuric acid DL- hyoscyamines, atropine or other derive by downstream product made of intermediate or atropine of atropine
Thing.Content of the atropic category medicine in eye drops is 0.001%~1% (w/v), preferably 0.005%~0.1% (w/
V), more preferably 0.01%~0.1% (w/v).
In one embodiment of the invention, the example of the lubrication, solubilising and moisturizing solute includes polyethylene glycol, sweet
Oil, propane diols, chondroitin sulfate, methylcellulose class are (such as：Hydroxypropyl methyl cellulose HPMC and carboxyl methyl cellulose),
Sodium Hyaluronate, hyaluronic acid, dipotassium glycyrrhizinate, Tweens, hydrochloric acid ammonium laurate, polyvinylpyrrolidone (PVP), polyethylene
One or several kinds of combinations of alcohol (PVA), dextran, chitosan etc., preferably glycerine, polyethylene glycol, Sodium Hyaluronate.Institute
It is 0%~10% (w/v), preferably 0.01%~5% (w/v), more preferably 0.01%~1% to state content of the solute in eye drops
(w/v), most preferably 0.01%~0.1% (w/v).
In one embodiment of the invention, the example of soda acid (pH) conditioning agent includes disodium hydrogen phosphate, phosphoric acid
Sodium dihydrogen, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, tartaric acid, acetic acid, sodium acetate, boric acid and its salt, borax, citric acid, citric acid
One or more in sodium, preferably sodium carbonate-bicarbonate buffer solution, dibastic sodium phosphate-disodium hydrogen phosphate buffer solution.PH adjusting agent
The acid-base value of eye drops can be made equal or close with the acid-base value of ocular fluid, reduce the excitant of eye drops, improve curative effect, ensured
The stability of medicine.The dosage of pH adjusting agent is adjusted to 6.0~8.0 by pH to be defined, and the dosage of preferably pH adjusting agent is adjusted with pH
It is defined to 6.5~7.5.
In one embodiment of the invention, the example of the osmotic pressure regulator include sodium chloride, boric acid, borax,
One or several kinds in glucose etc., preferably sodium chloride and glucose.The amount of the osmotic pressure regulator is adjusted with osmotic pressure
It is defined to 280~380mOsm/L, the dosage of preferably osmotic pressure regulator is adjusted to 290~330mOsm/L by osmotic pressure to be defined,
The dosage of more preferably osmotic pressure regulator is adjusted to 300~320mOsm/L by osmotic pressure to be defined.The effect of osmotic pressure regulator is
In order that the osmotic pressure of eye drops is equal or close with the osmotic pressure of ocular fluid, the excitant of eye drops is reduced, improves curative effect.
In one embodiment of the invention, the example of the thickener includes methylcellulose, polyvinyl alcohol, poly- second
Glycol, dextran, carboxymethyl cellulose, carboxylic propyl methocel, polyvinylpyrrolidone, POLYPROPYLENE GLYCOL, hyaluronic acid
One or more in sodium, chitosan, chondroitin sulfate etc., preferably clear matter acid sodium, polyethylene glycol.The dosage of the thickener
It is defined by adjusting solution viscosity to 6~10mps, the dosage of preferred thickener is defined to 7~9mps by adjusting solution viscosity.Thickening
Agent can extend the time that eye drops is detained within the eye, improve curative effect, while mitigate stimulation of the preparation to eye mucous membranes.
In one embodiment of the invention, it is described that there is the example for stablizing the pharmaceutically-active solute of atropic category to include
Acetonate, α and bata-carotene, taurine, vitamin E, vitamin B6 and other there is the vitamins of identical effect, it is described
It is 0.001%~1% (w/v) with content of the pharmaceutically-active solute of atropic category in eye drops is stablized, is preferably
0.005%~0.5% (w/v), more preferably 0.01%~0.3% (w/v)；
In embodiments of the invention, if including bacteriostatic agent, the example of the bacteriostatic agent includes boric acid, oxybenzene
Ethyl ester, methyl hydroxybenzoate, Nipasol, phenylmercuric acetate, sorbic acid, anesin, sulphur Liu Gong, benzalkonium chloride, benzalkonium bromide, it is excellent
Select benzalkonium chloride, benzalkonium bromide.Content of the bacteriostatic agent in eye drops is 0.001%~0.1% (w/v), preferably
0.005%~0.05% (w/v), most preferably 0.01%~0.03% (w/v).
In addition, the present invention also provides the preparation method of low concentration atropic category medicament dropping ocular fluid, it comprises the following steps：
A. atropic category medicine is made into the aqueous solution that concentration is 0.001%~1% (w/v),
B. then into step a in resulting solution add 0%~10% (w/v) have lubrication, solubilising and moisture-keeping function
Solute, and be well mixed,
C. acid-base modifier and then into step b resulting solutions is added, its pH is adjusted to 6.0~8.0,
D. osmotic buffering agent is added into step c resulting solutions, its osmotic pressure is adjusted to 280~380mOsm/L,
E. thickener is added into step d resulting solutions again, its viscosity is adjusted to 6~10mps,
F. into step e resulting solutions, 0.001%~1% (w/v) of addition is pharmaceutically-active with atropic category is stablized again
Solute；
G. finally by added in step f resulting solutions 0%~0.1% (w/v) bacteriostatic agent and optional 0%~
0.1% (w/v) peppermint, natural borneol, vitamin B6, dipotassium glycyrrhizinate or other have one kind in booster action material or
Sterilized after a variety of and filling, produce low concentration atropic category medicament dropping ocular fluid finished product.
In one embodiment of the invention, the sterilizing methods are membrane filtration or hot-press method, or dry
Hot method, radiation method, ultraviolet sterilization method and inspissation etc.；Aseptic filling method is that single, sterile unit dose is filling, also may be used
Think multiple dose sterile filling.
The eye drops of the present invention can be the eye-drops preparations of following formulation：Such as eye drops, eyewash, intraocular injection solution, or
Eye ointment, eye mask agent, gel for eye use etc. is made by other suitable preparation methods.
It is used for the purposes for preventing and delaying adolescent myopia present invention also offers low concentration atropic category medicament dropping ocular fluid,
Specifically, the low concentration atropic category medicament dropping ocular fluid can be the previously described low concentration atropic category medicine of the present invention
Eye drops.
Embodiment 1
Bulk drug atropine sulfate is added in water for injection, is made into the aqueous solution that concentration is 0.001% (w/v), then
Glycerine is added wherein, and it is 0.01% (w/v) to make its concentration, after being well mixed, adds vitamin E, and it is 0.01% to make its concentration
(w/v) it is 7.5, to adjust pH with sodium carbonate-bicarbonate cushioning liquid, and it is 303mOsm/L to adjust osmotic pressure with sodium chloride, uses hydroxypropyl
It is 9.0mps that methylcellulose, which adjusts viscosity, is sterilized using the method for 0.22 μm of membrane filtration, then using single, sterile unit dose
It is filling, produce sterile low-concentration sulfuric acid atropine eye drops.
Embodiment 2
Bulk drug atropine sulfate is added in water for injection, be made into concentration be 0.01% (w/v) the aqueous solution, then
Polyethylene glycol is wherein added, it is 0.02% (w/v) to make its concentration, after being well mixed, adds taurine, it is 1% (w/ to make its concentration
V), it is 6.9 to adjust pH with dibastic sodium phosphate-sodium dihydrogen phosphate buffer, and it is 310mOsm/L to adjust osmotic pressure with glucose, and use is transparent
It is 7.6mps that matter acid sodium, which adjusts viscosity, is sterilized using the method for hot pressing, then filling using single, sterile unit dose, is produced sterile low
Concentration sulphuric acid atropine eye drops.
Embodiment 3
Bulk drug atropine sulfate is added in water for injection, be made into concentration be 0.1% (w/v) the aqueous solution, then
Sodium Hyaluronate is wherein added, it is 0.01% (w/v) to make its concentration, after being well mixed, adds vitamin E, and it is 1% to make its concentration
(w/v) it is 7.4, to adjust pH with dibastic sodium phosphate-disodium hydrogen phosphate, and it is 305mOsm/L to adjust osmotic pressure with sodium chloride, uses hydroxypropyl methyl
It is 8.0mps that cellulose, which adjusts viscosity, is sterilized using the method for 0.22 μm of membrane filtration, then filling using single, sterile unit dose,
Produce sterile low-concentration sulfuric acid atropine eye drops.
Embodiment 4
Bulk drug atropine sulfate is added in water for injection, is made into the aqueous solution that concentration is 1% (w/v), then at it
Middle addition glycerine, it is 0.01% (w/v) to make its concentration, after being well mixed, adds vitamin E, it is 0.01% (w/ to make its concentration
V), it is 7.0 to adjust pH with sodium carbonate-bicarbonate cushioning liquid, and it is 310mOsm/L to adjust osmotic pressure with sodium chloride, with hydroxypropyl first
It is 8.2mps that base cellulose, which adjusts viscosity, is sterilized using the method for 0.22 μm of membrane filtration, is then filled using single, sterile unit dose
Dress, produces sterile low-concentration sulfuric acid atropine eye drops.
Embodiment 5
Bulk drug atropine sulfate is added in water for injection, be made into concentration be 0.1% (w/v) the aqueous solution, then
Polyethylene glycol is wherein added, it is 0.01% (w/v) to make its concentration, after being well mixed, adds taurine, and it is 0.1% to make its concentration
(w/v) it is 7.5, to adjust pH with dibastic sodium phosphate-disodium hydrogen phosphate, and it is 315mOsm/L to adjust osmotic pressure with glucose, uses hydroxypropyl methyl
It is 9.0mps that cellulose, which adjusts viscosity, is sterilized using the method for hot pressing, then filling using single, sterile unit dose, is produced sterile low
Concentration sulphuric acid atropine eye drops.
Embodiment 6
Bulk drug atropine sulfate is added in water for injection, be made into concentration be 0.1% (w/v) the aqueous solution, then
Polyethylene glycol is wherein added, it is 0.01% (w/v) to make its concentration, after being well mixed, adds taurine, and it is 0.5% to make its concentration
(w/v) it is 7.5, to adjust pH with dibastic sodium phosphate-disodium hydrogen phosphate, and it is 315mOsm/L to adjust osmotic pressure with glucose, uses hydroxypropyl methyl
It is 9.0mps that cellulose, which adjusts viscosity, is sterilized using the method for hot pressing after adding 0.01% (w/v) bacteriostatic agent, then used
Multiple dose sterile filling, produce sterile low-concentration sulfuric acid atropine eye drops.
Embodiment 7
Bulk drug atropine sulfate is added in water for injection, be made into concentration be 0.01% (w/v) the aqueous solution, then
Sodium Hyaluronate is wherein added, it is 0.01% (w/v) to make its concentration, after being well mixed, adds taurine, makes its concentration be
0.1% (w/v), it is 7.3 to adjust pH with dibastic sodium phosphate-carbonic acid sodium dihydrogen cushioning liquid, and it is 300mOsm/ to adjust osmotic pressure with sodium chloride
L, it is 9.0mps to adjust viscosity with hydroxypropyl methyl cellulose, is sterilized using the method for 0.22 μm of membrane filtration, then used
Single, sterile unit dose is filling, produces sterile low-concentration sulfuric acid atropine eye drops.
Study on the stability
In order to investigate use sterile low-concentration sulfuric acid atropine eye drop preparation made from this method stability, using with
The method of machine sampling, selection in eye drops made from the method for embodiment 7 using some bottles are extracted, using high performance liquid chromatography
Carrying out content tracing detection to main ingredient atropine sulfate therein, (main ingredient component content excursion >=5%, which is considered as, to be taken place
Change, >=10% is considered as failure), and carry out Method validation experiment and investigate.Using temperature, illumination, pH and storage time as change
Change amount, the medicine main ingredient stability is investigated.Range of temperature is：20~100 DEG C, pH excursions are:3~9, light
According to accelerated test：In the light cupboard of exposure intensity 4000~5000, storage time is：0~18 month.As a result show：Take into account human body
Eyes are considered the stability of the tolerance degree scope and eye drops of eye drops in itself, are 6~8 in pH scopes, temperature range 20
~40 DEG C, in the case of avoiding strong illumination, sterile low-concentration sulfuric acid atropine eye drops can keep not losing for 9 months
Effect, be 6.5~7.5 in pH scopes, 20~25 DEG C of temperature range, in the case of avoiding strong illumination, sterile low-concentration sulfuric acid Ah
Tropine eye drops can keep not changing substantially for 9 months.
Application Example
In order to further prove the actual effect of the eye drops of the present invention, medical institutions are entrusted, using the side of randomized double-blind
Method, clinical test is carried out from the eye drops in embodiment 7, subjects are near-sighted youngster of 400 ages in 6~12 one full year of life
Child, mypia progression are：The power range of at least one hypometropia is【- 1.0D~-5.0D】, application method is：At random
Wherein 200 children with myopia are chosen as compareing, to remaining 200 children with myopia medications, by the eye drip of the embodiment of the present invention 7
Drop enters in the eyes with myopia, 2 times a day, one time 2~3 drop.After 24 months, after testing, this eye drops is not instilled
Children, the diopter amplitude of variation of hypometropia is【-2.58±1.16D】, and the eyes for instilling the children of this eye drops are near
The diopter amplitude of variation regarded as【-0.54±0.36D】, confidential interval 95%, and by medical practitioner to medication children such as
The test result of pupil dilation etc. shows that eye drops of the invention does not substantially damage to the eyes of the children with myopia of medication
And side effect, while effectively can prevent and delay the obvious increase of the child myopia number of degrees.
The preferred embodiment of invention is the foregoing is only, is not intended to limit the invention, for the ordinary skill of this area
For personnel, other various corresponding changes can be made with technique according to the invention scheme and technical concept, ensure the present invention
Other beneficial effects enumerated in the effect of described and specification.
Claims (10)
1. a kind of low concentration atropic category medicament dropping ocular fluid, it is made up of following each component：
(A) atropic category medicine, 0.001%~1% (w/v)；
(B) there is the solute of lubrication, solubilising and moisture-keeping function, 0%~10% (w/v)；
(C) acid-base modifier, its amount is adjusted to 6.0~8.0 by pH to be defined；
(D) osmotic buffering agent, its amount is adjusted to 280~380mOsm/L by osmotic pressure to be defined；
(E) thickener, its amount is adjusted to 6~10mps by viscosity to be defined；
(F) have and stablize the pharmaceutically-active solute of atropic category, 0.001%~1% (w/v)；
(G) bacteriostatic agent, 0%~0.1% (w/v)；
Also can be optionally added peppermint, natural borneol, vitamin B6, dipotassium glycyrrhizinate or other have in booster action material
One or more, 0%~0.1% (w/v)；
Surplus is water.
2. low concentration atropic category medicament dropping ocular fluid according to claim 1, it is characterised in that the bulk drug atropine
Class medicine by atropine sulfate, sulfuric acid atropina, sulfuric acid DL- hyoscyamines, atropine or other be made up with atropine of intermediate
Downstream product or Atropine derivatives, content of the atropic category medicine in eye drops be 0.005%~0.1%
(w/v), more preferably 0.01%~0.1% (w/v).
3. low concentration atropic category medicament dropping ocular fluid according to claim 1, it is characterised in that described that there is lubrication, increase
The molten and solute of moisture-keeping function is polyethylene glycol, glycerine, propane diols, chondroitin sulfate, methylcellulose class (hydroxypropyl methyl fibre
Tie up plain HPMC and carboxyl methyl cellulose), Sodium Hyaluronate, hyaluronic acid, dipotassium glycyrrhizinate, Tweens, hydrochloric acid laurate
One or more in ammonium, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), dextran, chitosan, preferably glycerine,
Polyethylene glycol, Sodium Hyaluronate, content of the solute in eye drops are 0.01%~1% (w/v), preferably 0.01%~
0.1% (w/v).
4. low concentration atropic category medicament dropping ocular fluid according to claim 1, it is characterised in that described to use acid-base modifier
For disodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution, potassium dihydrogen phosphate-dipotassium hydrogen phosphate buffer solution, sodium carbonate-bicarbonate buffering
One or more in liquid, tartaric acid, acetic acid, sodium acetate, boric acid and its salt, borax, citric acid, sodium citrate, preferably carbonic acid
Sodium-sodium bicarbonate buffer liquid, dibastic sodium phosphate-disodium hydrogen phosphate buffer solution, the dosage of the acid-base modifier are adjusted to 6.0 with pH
~8.0 are defined, and the dosage of preferably acid-base modifier is adjusted to 6.5~7.5 by pH to be defined.
5. low concentration atropic category medicament dropping ocular fluid according to claim 1, it is characterised in that described to be buffered with osmotic pressure
Agent is the one or several kinds in sodium chloride, boric acid, borax, glucose, preferably sodium chloride and glucose, and the osmotic pressure buffers
The dosage of agent is adjusted to 290~330mOsm/L by osmotic pressure to be defined, preferably the dosage of osmotic pressure regulator with osmotic pressure adjust to
300~320mOsm/L is defined.
6. low concentration atropic category medicament dropping ocular fluid according to claim 1, it is characterised in that the thickener is methyl
Cellulose, polyvinyl alcohol, polyethylene glycol, dextran, carboxymethyl cellulose, carboxylic propyl methocel, polyvinylpyrrolidine
One or more in ketone, POLYPROPYLENE GLYCOL, Sodium Hyaluronate, chitosan, chondroitin sulfate, preferably clear matter acid sodium and poly- second two
Alcohol, the dosage of the thickener are defined to be adjusted by viscosity to 7~9mps.
7. low concentration atropic category medicament dropping ocular fluid according to claim 1, it is characterised in that it is described have stablize atropic
The pharmaceutically-active solute of category be selected from acetonate, α and bata-carotene, taurine, vitamin E, vitamin B6 and other have
The vitamins of identical effect, it is described have stablize content of the pharmaceutically-active solute of atropic category in eye drops and be
0.001%~1% (w/v).
8. low concentration atropic category medicament dropping ocular fluid according to claim 1, it is characterised in that the bacteriostatic agent is selected from boron
Acid, ethyl hydroxy benzoate, methyl hydroxybenzoate, Nipasol, phenylmercuric acetate, sorbic acid, anesin, sulphur Liu Gong, benzalkonium chloride, benzene are pricked
Bromine ammonium, preferably benzalkonium chloride, benzalkonium bromide, content of the bacteriostatic agent in eye drops are 0.005%~0.05% (w/v),
It is preferred that 0.01%~0.03% (w/v).
9. the preparation method of low concentration atropic category medicament dropping ocular fluid, it comprises the following steps：
A. atropic category medicine is made into the aqueous solution that concentration is 0.001%~1% (w/v),
B. then having for 0%~10% (w/v) is added in resulting solution into step a lubricate, be solubilized and moisture-keeping function molten
Matter, and be well mixed,
C. acid-base modifier and then into step b resulting solutions is added, its pH is adjusted to 6.0~8.0,
D. osmotic buffering agent is added into step c resulting solutions, its osmotic pressure is adjusted to 280~380mOsm/L,
E. thickener is added into step d resulting solutions again, its viscosity is adjusted to 6~10mps,
F. again into step e resulting solutions add 0.001%~1% (w/v) have stablize the pharmaceutically-active solute of atropic category；
G. finally by the bacteriostatic agent that 0%~0.1% (w/v) is added in step f resulting solutions and 0%~0.1% optional (w/
V) peppermint, natural borneol, vitamin B6, dipotassium glycyrrhizinate or other have it is one or more laggard in booster action material
Row sterilizing is simultaneously filling, produces low concentration atropic category medicament dropping ocular fluid finished product.
10. low concentration atropic category medicament dropping ocular fluid is used for the purposes for preventing and delaying adolescent myopia.
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Application publication date: 20171212 |