CN106137954A - Comprise eye drop with stable viscosity of polyhydric alcohol inorganic salt xanthan gum ternary system and preparation method thereof - Google Patents

Comprise eye drop with stable viscosity of polyhydric alcohol inorganic salt xanthan gum ternary system and preparation method thereof Download PDF

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Publication number
CN106137954A
CN106137954A CN201610666374.6A CN201610666374A CN106137954A CN 106137954 A CN106137954 A CN 106137954A CN 201610666374 A CN201610666374 A CN 201610666374A CN 106137954 A CN106137954 A CN 106137954A
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xanthan gum
polyhydric alcohol
inorganic salt
ternary system
eye drop
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张真真
廉云飞
张军东
吴剑英
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SHANGHAI HAOHAI BIOLOGICAL TECHNOLOGY Co Ltd
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SHANGHAI HAOHAI BIOLOGICAL TECHNOLOGY Co Ltd
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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions

Abstract

The invention belongs to pharmaceutical technology field, relate to eye drop with stable viscosity comprising polyhydric alcohol inorganic salt xanthan gum ternary system and preparation method thereof, including: moxifloxacin hydrochloride 0.5～0.6%w/v；Xanthan gum 0.5～0.8%w/v；Multicomponent alcoholics compound 0.1～1%w/v；Isoosmotic adjusting agent 0.3～0.9%w/v；The rest is water for injection and PH regulator, the present invention improves the degradation problem after tackifier xanthan gum sterilizing, improve ionic strength and add antioxidant solubility alcohols, form polyhydric alcohol inorganic salt xanthan gum ternary system, after making its sterilizing, viscosity does not declines, it is ensured that eye drop is 40 80pa s at the static viscosity of eye；The bioavailability of improvement is provided, it is possible to more effectively treat eye inflammation, and the contact angle of this product is less, the wetting action of part tissue of eye can be increased, there is no adhesive sensation, substantially increase the compliance of patient for eye drop.

Description

Comprise the eye drip with stable viscosity of polyhydric alcohol-inorganic salt-xanthan gum ternary system Liquid and preparation method thereof
Technical field
The invention belongs to pharmaceutical technology field, be specifically related to a kind of containing polyhydric alcohol-inorganic salt-xanthan gum ternary system There is stable viscosity eye drop and preparation method thereof.
Background technology
Dosing eyes system is a kind of drug delivery system with local therapeutic effects feature, is mainly used in clinically killing Bacterium, antiinflammatory, mydriasis, anaesthetize, treat glaucoma, reduce intraocular pressure etc..At present the form of ophthalmic remedy be broadly divided into eye drip liquor, The modes such as eye drip oil preparation, eye ointment, gel, subconjunctival injection and intravitreal injection.Shed tears and blink owing to eyes have instead The very effective protection mechanism such as penetrate, make the medicinal liquid being added dropwise to ophthalmic eliminate from cornea forefoot area rapidly, and eye ointment and gel Viscosity is relatively big, makes patient uncomfortable, thus these dosage forms also exist certain deficiency the most to a certain extent.
Xanthan gum (Xanthan gum) is that production scale is maximum and the most commonly used microorganism of purposes is many most in the world Sugar, forms high viscosity solution after good water solubility, fully hydration, is widely used in the necks such as food, medicine, chemical industry as thickening agent Territory.Owing to eyes are about 0.03s in intermittent periods shear rate-1, nictation period shear rate be 4250-28500s-1.Yellow Virgin rubber is a kind of pseudoplastic fluid, can simulate the biological characteristic of part tissue of eye nictation, when administered, due to the high viscosity of xanthan gum Make it preferably attach on conjunctiva, and when the nictation of eye reflections, the viscosity of xanthan gum declines again, promote it with glutinous Albumen effect, increases drug absorption.Owing to xanthan gum has certain viscosity, it is impossible to carry out filtration sterilization, by terminal sterilization 121 DEG C, the method for 15min can guarantee that product SAL≤10-6, but when xanthan gum exposes at high temperature, it may occur that from order to unordered Conformation transition process.Xanthan gum is when disordered state, and the viscosity of its aqueous solution is more much lower than order state.Xanthan gum is polymerized The free-radical oxidation reduction reaction of thing is autocatalytic free radical chain reaction mechanism, as follows:
First, xanthan gum at high temperature produces alkyl diradical R, then alkyl diradical R and the dissolving in solution Oxygen reaction generates peroxide.Peroxide is attacked xanthan molecules and is produced new alkyl diradical R, and reaction is so entered repeatedly OK, thus cause polymer chain break and degrade.
Moxifloxacin is forth generation broad-spectrum high efficacy fluoroquinolone antibiotics, Bayer company of Germany develop, 1999 9 The moon lists in Germany.Mechanism of action is suppression topoisomerase II and topoisomerase I V, blocks DNA of bacteria synthesis, the most excellent Gesture is that antimicrobial spectrum three generations's quinolones earlier above is wider, and resistant rate is extremely low, is 1.8 × 10-9—1×10-11, particularly do not allow Easy and other quinolone antibiotics produce crossing drug resistant, and clinical adverse is few, have become as clinical main antibiotic One of, its eye drop is the following ophthalmically acceptable antimicrobial drug of main flow, and antibacterial effect is better than like product.
Summary of the invention
In order to make up above deficiency, the invention provides a kind of tool containing polyhydric alcohol-inorganic salt-xanthan gum ternary system There is stable viscosity eye drop and preparation method thereof, to solve the problem in above-mentioned background technology.
The technical scheme is that
A kind of eye drop with stable viscosity comprising polyhydric alcohol-inorganic salt-xanthan gum ternary system, including following group Become:
Moxifloxacin hydrochloride 0.5～0.6%w/v；
Xanthan gum 0.5～0.8%w/v；
Multicomponent alcoholics compound 0.1～1%w/v；
Isoosmotic adjusting agent 0.3～0.9%w/v；
The rest is water for injection and PH regulator.
As a kind of preferred version, described isoosmotic adjusting agent is sodium chloride, and its consumption is 0.5～0.9%w/v.
As a kind of preferred version, described isoosmotic adjusting agent is potassium chloride, and its consumption is 0.3～0.6%w/v.
As a kind of preferred version, the pH value of eye drop is 5.0-8.0, and osmotic pressure is 300～450mOsm/Kg, at eye Static viscosity be 40-80pa s.
As a kind of preferred version, light transmittance >=80% of described xanthan gum.
As a kind of preferred version, described multicomponent alcoholics compound is sorbitol and mannitol one therein, described PH Regulator is hydrochloric acid or sodium hydroxide.
Present invention additionally comprises a kind of stable viscosity that has prepared and comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system The method of eye drop,
Step 1): precision weighs the xanthan gum of recipe quantity and isoosmotic adjusting agent is placed in water for injection, stirring, makes the most molten Swollen, cross 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add the multicomponent alcoholics compound of recipe quantity, dissolve standby；
Step 2): the moxifloxacin hydrochloride weighing recipe quantity is placed in residue water for injection, stirring, pH adjusting agent regulation pH To 5.0-8.0, stir；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization, condition respectively It is 121 DEG C of sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, stir, sterile filling, gained solution i.e. has surely Determine the eye drop of viscosity.
Described step 1) in isoosmotic adjusting agent be sodium chloride and potassium chloride one therein, sodium chloride consumption be 0.5～ 0.9%w/v, potassium chloride dosage is 0.3～0.6%w/v.
As a kind of preferred version, described multicomponent alcoholics compound is sorbitol and mannitol one therein, described PH Regulator is hydrochloric acid or sodium hydroxide.
The present invention is provided with advantages below: it is an advantage of the invention that being formed by polyhydric alcohol-inorganic salt-xanthan gum of creativeness Ternary system: the present invention is 40-80pa s at the static viscosity of eye, can improve the bioavailability of moxifloxacin hydrochloride, and Show the sensation of non-adhesiveness, not only increase the ionic strength in solution, improve conformation transition temperature；Polyhydric alcohol simultaneously As reproducibility compound, can be oxidized and stop the free-radical oxidation reduction reaction of xanthan polymer by self, make Huang Virgin rubber chain does not ruptures.Due to inorganic salt and polyhydric alcohol synergism, xanthan gum is when moist heat sterilization, and viscosity will not reduce, it is possible to After making this product sterilizing, the static viscosity at eye is 40-80pa s, on the one hand improves the biological utilisation of moxifloxacin hydrochloride Degree, on the other hand eye drop shows the sensation of non-adhesiveness, and wettability is preferable, and patient's compliance is higher.
The formula of the present invention and preparation technology, can improve the degradation problem after tackifier xanthan gum sterilizing, by improve from Sub-intensity and addition antioxidant solubility alcohols, form polyhydric alcohol-inorganic salt-xanthan gum ternary system so that it is viscosity after sterilizing Do not decline, it is ensured that eye drop is 40-80pa s at the static viscosity of eye.The present invention is the biology that eye drop provides improvement Availability, it is possible to more effectively treat eye inflammation, show the sensation of non-adhesiveness simultaneously, wettability is preferable, and patient complies with Property is higher.
Accompanying drawing explanation
Fig. 1 is the rheological curve comparison diagram of inventive formulation 1-4；
Fig. 2 is the contact angle figure of inventive formulation 1；
Fig. 3 is the contact angle figure of inventive formulation 2；
Fig. 4 is the contact angle figure of inventive formulation 3；
Fig. 5 is the contact angle figure of inventive formulation 4.
Detailed description of the invention
A kind of eye drop with stable viscosity comprising polyhydric alcohol-inorganic salt-xanthan gum ternary system, including following group Become:
Moxifloxacin hydrochloride 0.5～0.6%w/v；
Xanthan gum 0.5～0.8%w/v；
Multicomponent alcoholics compound 0.1～1%w/v；
Isoosmotic adjusting agent 0.3～0.9%w/v；
The rest is water for injection and PH regulator.
Described isoosmotic adjusting agent is sodium chloride, and its consumption is 0.5～0.9%w/v.
Described isoosmotic adjusting agent is potassium chloride, and its consumption is 0.3～0.6%w/v.
The pH value of eye drop is 5.0-8.0, and osmotic pressure is 300～450mOsm/Kg, and the static viscosity at eye is 40- 80pa·s。
Light transmittance >=80% of described xanthan gum.
Described multicomponent alcoholics compound is sorbitol and mannitol one therein, and described PH regulator is hydrochloric acid or hydrogen-oxygen Change sodium.
A kind of method preparing the eye drop with stable viscosity comprising polyhydric alcohol-inorganic salt-xanthan gum ternary system:
Step 1): precision weighs the xanthan gum of recipe quantity and isoosmotic adjusting agent is placed in water for injection, stirring, makes the most molten Swollen, cross 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add the multicomponent alcoholics compound of recipe quantity, dissolve standby；
Step 2): the moxifloxacin hydrochloride weighing recipe quantity is placed in residue water for injection, stirring, pH adjusting agent regulation pH To 5.0-8.0, stir；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization, condition respectively It is 121 DEG C of sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, stir, sterile filling, gained solution i.e. has surely Determine the eye drop of viscosity.
Described step 1) in isoosmotic adjusting agent be sodium chloride, its consumption is 0.5～0.9%w/v.
Described step 1) in isoosmotic adjusting agent be potassium chloride, its consumption is 0.3～0.6%w/v.
Described multicomponent alcoholics compound is sorbitol and mannitol one therein.
Described PH regulator is hydrochloric acid or sodium hydroxide.
For the technological means making the present invention realize, creation characteristic, reach purpose and be easy to understand with effect, below knot Close specific embodiment, the present invention is expanded on further.
Embodiment one,
Composition Prescription (%w/v)
Moxifloxacin hydrochloride 0.5
Xanthan gum 0.5
Sorbitol 0.1
Sodium chloride 0.8
NaOH/HCl Adjust pH to 5.0
Water for injection Add to 1000ml
Preparation method: following material feeds intake by recipe quantity
Step 1): precision weighs the sodium chloride of 5g xanthan gum and 5g and is slowly positioned in the container equipped with 400ml water for injection, 400rpm stirring 30min makes the most swelling, makes the most swelling, crosses 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add 1g's Sorbitol, dissolves standby；
Step 2): the moxifloxacin hydrochloride weighing 5g is placed in residue water for injection, stirring, and pH adjusting agent regulation pH is extremely 5.0, stir；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization, condition respectively It is 121 DEG C of sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, mend the water for injection after sterilizing to 1000ml, stirring is all Even, sterile filling, gained solution i.e. has the eye drop of stable viscosity.
Embodiment two,
Preparation method: following material feeds intake by recipe quantity
Step 1): precision weighs 8g xanthan gum and 9g sodium chloride is slowly positioned in the container equipped with 450ml water for injection, 400rpm stirring 40min makes the most swelling, crosses 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add the sorbitol of 10g, dissolve Standby；
Step 2): the moxifloxacin hydrochloride weighing 6g is placed in residue water for injection, stirring, and pH adjusting agent regulation pH is extremely 8.0, stir；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization, condition respectively It is 121 DEG C of sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, mend the water for injection after sterilizing to 1000ml, stirring is all Even, sterile filling, gained solution i.e. has the eye drop of stable viscosity.
Embodiment three,
Composition Prescription A (%w/v)
Moxifloxacin hydrochloride 0.5
Xanthan gum 0.5
Mannitol 0.1
Potassium chloride 0.3
NaOH/HCl Adjust pH to 5.0
Water for injection Add to 1000ml
Preparation method: following material feeds intake by recipe quantity
Step 1): precision weighs 5g xanthan gum and 3g potassium chloride is slowly positioned in the container equipped with 500ml water for injection, 400rpm stirring 35min makes the most swelling, crosses 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add 1g mannitol, dissolve standby With；
Step 2): weigh 5g moxifloxacin hydrochloride and be placed in residue water for injection, stirring, pH adjusting agent regulation pH to 5.0, Stir；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization, condition respectively It is 121 DEG C of sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, mend the water for injection after sterilizing to 1000ml, stirring is all Even, sterile filling, gained solution i.e. has the eye drop of stable viscosity.
Embodiment four,
Composition Prescription A (%w/v)
Moxifloxacin hydrochloride 0.6
Xanthan gum 0.8
Mannitol 1
Potassium chloride 0.6
NaOH/HCl Adjust pH to 8.0
Water for injection Add to 1000ml
Preparation method: following material feeds intake by recipe quantity
Step 1): precision weighs 8g xanthan gum and 6g potassium chloride is placed in the container equipped with 400ml water for injection slowly, 400rpm stirring 30min makes the most swelling, and stirring makes the most swelling, crosses 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add 10g mannitol, dissolves standby；
Step 2): the moxifloxacin hydrochloride weighing 6g is placed in residue water for injection, stirring, and pH adjusting agent regulation pH is extremely 8.0, stir；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization, condition respectively It is 121 DEG C of sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, mend the water for injection after sterilizing to 1000ml, stirring is all Even, sterile filling, gained solution i.e. has the eye drop of stable viscosity.
Embodiment five,
Preparation method: following material feeds intake by recipe quantity
Step 1): precision weighs 7g xanthan gum and 6g potassium chloride is slowly positioned in the container equipped with 400ml water for injection, 400rpm stirring 30min makes the most swelling, crosses 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add 5g sorbitol, dissolve standby With；
Step 2): weighing 5.45g moxifloxacin hydrochloride and be placed in residue water for injection, stirring, pH adjusting agent regulation pH is extremely 7.5, stir；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization, condition respectively It is 121 DEG C of sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, mend the water for injection after sterilizing to 1000ml, stirring is all Even, sterile filling, gained solution i.e. has the eye drop of stable viscosity.
The solution of the present invention is: for proving that the present invention has substantive distinguishing features and significantly progress, carry out test further, The formula made according to embodiment five participates in the experiment of other three group of formula and carries out every data experiment test, system as shown in the table Standby:
Table 1 eye drop 1-4 formula
Formula 1: according to the eye drop with stable viscosity of embodiment five preparation.
Formula 2: prepare the solution (i.e. without sorbitol) without multicomponent alcoholics compound according to embodiment five.
Formula 3: prepare the solution (i.e. without potassium chloride) without isoosmotic adjusting agent according to embodiment five.
Formula 4: according to embodiment five prepare both without isoosmotic adjusting agent also without the solution of multicomponent alcoholics compound (not containing sorbitol and potassium chloride).
Four groups of prescription performance tests
Take from four group of formula its appearance character of sample detection of preparation, moxifloxacin hydrochloride content, pH value, osmotic pressure, Static viscosity, contact angle.
1. viscosity detection: use U.S.'s TA flow graph, selecting fixture is 20mm cone-plate, and tapering 1 °, range of shear rate is 0.001-4000/s, carries out shear rate-viscosity curve scanning, obtains the rheological curve comparison diagram of Fig. 1 formula 1-4.
2. contact angle test: use the detection of XG-CAM contact angle tester, the principle test of optically-based image analysis Liquid the surface of solids formed contact angle size, it is judged that this product wellability to eye conjunctiva, its gas-liquid interface and Solid liquid interface two tangent line is clipped in wherein formed angle liquid phase and is contact angle, is detected by XG-CAM contact angle tester, Obtain the contact angle figure of Fig. 2 formula 1；The contact angle figure of Fig. 3 formula 2；The contact angle figure of Fig. 4 formula 3；The contact angle of Fig. 5 formula 4 Figure, contrasts Fig. 2 to Fig. 5, it is known that the contact angle of formula 1 is minimum.
3. indices testing result: other conventional projects are according under Chinese Pharmacopoeia version annex in 2015 and ophthalmic preparation item Regulation test.The results are shown in Table 1.
Table 1 formula 1-4 each Indexs measure result
From result, the present invention can improve the degradation problem after tackifier xanthan gum sterilizing, by formed polyhydric alcohol- Inorganic salt-xanthan gum ternary system so that it is after sterilizing, viscosity does not declines, it is ensured that eye drop is 40-at the static viscosity of eye 80pa s, shows the sensation of non-adhesiveness simultaneously；And the contact angle of the present invention is less, the moistening that can increase part tissue of eye is made With.Therefore one aspect of the present invention adds the bioavailability of moxifloxacin hydrochloride, on the other hand substantially increase complying with of patient Property.
The above only depicts the ultimate principle of the present invention, principal character and advantages of the present invention.The skill of the industry The art personnel simply explanation it should be appreciated that the present invention is not restricted to the described embodiments, described in above-described embodiment and description The principle of the present invention, without departing from the spirit and scope of the present invention, the present invention also has various changes and modifications, these Changes and improvements both fall within scope of the claimed invention.Claimed scope by appending claims and Its equivalent circle.

Claims (9)

1. the eye drop with stable viscosity comprising polyhydric alcohol-inorganic salt-xanthan gum ternary system, it is characterised in that Including forming as follows:
Moxifloxacin hydrochloride 0.5～0.6%w/v；
Xanthan gum 0.5～0.8%w/v；
Multicomponent alcoholics compound 0.1～1%w/v；
Isoosmotic adjusting agent 0.3～0.9%w/v；
The rest is water for injection and PH regulator.
A kind of comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system have stable viscosity drip Ocular fluid, it is characterised in that: described isoosmotic adjusting agent is sodium chloride, and its consumption is 0.5～0.9%w/v.
A kind of comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system have stable viscosity drip Ocular fluid, it is characterised in that: described isoosmotic adjusting agent is potassium chloride, and its consumption is 0.3～0.6%w/v.
A kind of comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system have stable viscosity drip Ocular fluid, it is characterised in that: the pH value of eye drop is 5.0-8.0, and osmotic pressure is 300～450mOsm/Kg, and the static state at eye sticks Degree is 40-80pa s.
A kind of comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system have stable viscosity drip Ocular fluid, it is characterised in that: light transmittance >=80% of described xanthan gum.
A kind of comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system have stable viscosity drip Ocular fluid, it is characterised in that: described multicomponent alcoholics compound is sorbitol and mannitol one therein, and described PH regulator is salt Acid or sodium hydroxide.
7. the tool comprising polyhydric alcohol-inorganic salt-xanthan gum ternary system prepared as described in any one of claim 1 to 6 The method having the eye drop of stable viscosity, it is characterised in that:
Step 1): precision weighs the xanthan gum of recipe quantity and isoosmotic adjusting agent is placed in water for injection, stirring, makes the most swelling, Cross 5 μm and two grades of filter membranes of 1 μm must clarify subsequent filtrate, add the multicomponent alcoholics compound of recipe quantity, dissolve standby；
Step 2): the moxifloxacin hydrochloride weighing recipe quantity is placed in residue water for injection, stirring, and pH adjusting agent regulation pH is extremely 5.0-8.0, stirs；
Step 3): by step 1) dissolve after solution and step 2) uniformly after solution high pressure steam sterilization respectively, condition is 121 DEG C sterilizing 15min, is cooled to room temperature；
Step 4): step 3 will be completed) solution mix, stir, sterile filling, gained solution i.e. has and stably sticks The eye drop of degree.
A kind of prepare comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system there is stable viscosity The method of eye drop, it is characterised in that: described step 1) in isoosmotic adjusting agent be sodium chloride or potassium chloride, sodium chloride consumption Being 0.5～0.9%w/v, potassium chloride dosage is 0.3～0.6%w/v.
A kind of prepare comprise polyhydric alcohol-inorganic salt-xanthan gum ternary system there is stable viscosity The method of eye drop, it is characterised in that: described multicomponent alcoholics compound is sorbitol and mannitol one therein, described PH Regulator is hydrochloric acid or sodium hydroxide.
CN201610666374.6A 2016-08-12 2016-08-12 Comprise eye drop with stable viscosity of polyhydric alcohol inorganic salt xanthan gum ternary system and preparation method thereof Pending CN106137954A (en)

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CN114392231A (en) * 2022-01-07 2022-04-26 华北制药股份有限公司 Natamycin eye drops and preparation method thereof
CN114652866A (en) * 2020-12-23 2022-06-24 上海其胜生物制剂有限公司 Damp-heat sterilization method for carboxymethyl chitin solution

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