CN1268344C - Puerarin gelation for eye use and prepn. method - Google Patents

Puerarin gelation for eye use and prepn. method Download PDF

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CN1268344C
CN1268344C CN 02145139 CN02145139A CN1268344C CN 1268344 C CN1268344 C CN 1268344C CN 02145139 CN02145139 CN 02145139 CN 02145139 A CN02145139 A CN 02145139A CN 1268344 C CN1268344 C CN 1268344C
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puerarin
gel
injection
water
ophthalmic
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CN1498624A (en
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韩红路
邹庆宇
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All American World China Pharmaceutical Co ltd
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PHARMACEUTICAL CO Ltd OF ZHEJIANG UNIV
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Abstract

The present invention relates to a puerarin ophthalmic gel for treating the chronic eye diseases of various kinds of glaucoma, arteria retina obstruction, arteria vein obstruction, etc. The main component is puerarin, the gel base is carbomer, and borax and boric acid are used as pH value regulating agents. 100 parts by the weight of gel contains 0.5 to 2.0 parts by the weight of puerarin, 0.1 to 1.0 part by the weight of gel base and water for injection as the rest, and pH value is regulated from 5.0 to 7.0. Compared with an eye drop, the prepared puerarin gel of the present invention has earlier drug effect action time and longer drug effect acting time, and is ideal medicine for resisting glaucoma.

Description

Puerarin ophthalmic gel and preparation method thereof
Technical field
The present invention relates to be used for the puerarin ophthalmic gel of chronic curing eye diseases such as all kinds glaucoma, moving (quiet) arteries and veins obstruction of retina, also relate to the preparation method of this gel.
Prior art
The active ingredient of puerarin (puerarin) for separating in conventional Chinese medicine Herba Gelsemii Elegantis pueraria labata (willd.) Ohwi (P.thunbergeriana S.et Z.) Benth.P.pseudohirsuta Tang et Wang and Radix Puerariae rattan (Pachyrhizua angulatus) the pueraria homsonii Benth root, its chemical name 8-β-D glucopyanosyl-4 ', 7-dihydroxy isoflavone [ophthalmology new development 1999,19 (2): 73～77].These product are white, needle-shaped crystals, can be water-soluble, but dissolubility low (6.24g/L), aqueous solution is colourless or little yellow [ophthalmology new development 2000,20 (6): 454～455].Puerarin has been approved for the Western medicine new drug, and dosage form has injection and eye drop, and puerarin raw material and injection are recorded by Chinese Pharmacopoeia version enlarged edition in 2000.
Glaucoma be with intraocular pressure increase constantly or discontinuously, defect of visual field, optic papilla sunken and atrophy and visual deterioration be a kind of disease of principal character.Sickness rate is about 1%～2% in the population of China, and in total blindness people, it is due to the glaucoma that 10% blind person is arranged approximately.Puerarin has the beta receptor retardation, can reduce intraocular pressure [Intraocular Pressure, IOP], and can improve optical fundus microcirculation [Chinese Journal of Ophthalmology 1999,29 (6): 336].10g/L puerarin eye drop (Nanjing Pharmaceuticals Inst's ophthalmology pharmacology research center development) shows the tool reducing iop, acute ocular hypertension model test is shown that tool suppresses intraocular pressure rising effect [Chinese Pharmacological circular 1998,14 (6): 569～570] chronic eye high pressure model test.1% puerarin eye drop is used for the treatment of primary open angle glaucoma, and it is the back 15min that puts drops in one's eyes that intraocular pressure begins to descend the fastest, is 4h the most slowly, the intraocular pressure the shortest 3h that holds time that descends, the longest 10h[combination of Chinese and Western medicine ophthalmology magazine 1992,10 (2): 65～67].
Summary of the invention
Task of the present invention provides a kind of puerarin ophthalmic gel, this gel is to be got by changing dosage form by the puerarin eye drop, on indication and the on all four basis of former eye drop dosage form, that the puerarin ophthalmic gel has is more rapid-action than eye drop, be easy to coating, nonirritant, medicine the time of staying is long within the eye, drug treating time is long and advantages such as good effect, is particularly suitable for glaucoma, the retina artery and vein blocks this class needs the patient of long-term treatment to use.
For realizing above-mentioned task, the present invention has taked following technical measures:
Puerarin ophthalmic gel of the present invention is to be main active ingredient with puerarin, be aided with gel base material, pH regulator agent, water for injection, in 100 parts of gel weight, puerarin is 0.5～2.0, the gel base material is 0.1～1.0, with Borax, boric acid is the pH regulator agent, regulates pH value 5.0～7.0, and all the other are water for injection.
The better formula of puerarin ophthalmic gel of the present invention is: in 100 parts of gel weight, puerarin is 0.8～1.5, and the gel base material is 0.2～0.6, is the pH regulator agent with Borax, boric acid, regulates pH value 6.0～6.5, and all the other are water for injection.
Gel base material of the present invention is a carbomer.
The preparation method of puerarin ophthalmic gel of the present invention is: puerarin dissolves with water for injection, then gel base material carbomer is soaked wherein 12h.PH value regulator Borax, boric acid are added wherein, stir, control pH value 5.0～7.0, add to the full amount of water for injection, fully stir, filter with 220 mesh sieve cloth, get clear gel, pressure sterilizing cools off then, and packing promptly obtains gel of the present invention.
Good effect of the present invention is:
Glaucoma, the retina artery and vein blocks as a kind of chronic disease, needs long-term prescription, and wish medicine within the eye the time of staying long, medicine performance maximum effect.The puerarin ophthalmic gel is gel-type vehicle with the carbomer, the skeleton that is chain connection, adhesion that carbomer is made up of the polymer that is full of moisture content, this polymer has unique thixotropy: promptly its structure under external force can be destroyed, causes viscosity to reduce; Through resting and reorganizing, its agglutinating gel skeleton can be rebuild again, and gelinite returns to original viscosity.The puerarin ophthalmic gel splashes into the collision effect that produced owing to nictation before this behind the ophthalmic, make gel show thixotropy, next is electrolytical hydrolysis of ophthalmic and Temperature Influence, moisture in the gel can balancedly be discharged in a large number, disperse is shown at eye fast, can substitute two layers of tear film (water liquid layer and mucin layer) simultaneously, prolong adhering to the time at the eye table.Therefore, the puerarin ophthalmic gel made of the present invention have that release is fast, no greasy, easily be coated with exhibition, can with characteristics such as aqueous solution and energy prolong drug action time.
The ophthalmic pharmacokinetic shows, the gel for eye use that puerarin is made, by this local application's approach, can be good at being absorbed the performance drug action by ocular tissue, the peak concentration of medicine appears at 2h, the minimum point that intraocular pressure descends illustrates that at 4h drug effect has hysteresis, and medicine is eliminated the half-life (t1/2 β) and is 8.32h in aqueous humor, 24h still can keep than ocular hypotension after once dripping medicine, illustrates that the drug action time is long; The puerarin eye drop dripped 3 times in one day, and the puerarin ophthalmic gel only needed to drip once in one day.
Effect experiment shows that also the puerarin ophthalmic gel has the thrombotic effect of Chinese People's Anti-Japanese Military and Political College Mus simultaneously; Obviously change rat blood stasis model blood rheology parameter; Improve the lagophthalmos bulbar Conjunctiva Microcirculation; Reduce the high intraocular pressure of Experimental Rabbits, and the puerarin ophthalmic gel is more Zao than the drug action time of eye drop, the performance drug action time is long, has obtained beyond thought effect.
The detailed description of the invention
To be Zinn's artery thicken because of the blood vessel wall sclerosis causes tube wall central retinal artery occlusion, narrow, thrombosis or vasospasm, the retinal artery occlusion due to embolus comes off.Central retinal vein occlusion is characterized as the tortuous expansion of retinal vein to be had hemorrhage, edema and oozes out etc. along the vein of getting involved.Primary disease cause of disease more complicated is often caused by multiple factor, with hypertension, arteriosclerosis, hyperlipidemia, blood viscosity and hematodinamics etc. the relation of connecting airtight is arranged all.Puerarin belongs to different osajin, has beta-receptor blocking effect widely, also has a microcirculation improvement effect.Radix Puerariae have and reduces intraocular pressure and improve the microcirculatory dual function of eye, is very favourable to the treatment glaucoma.Recent research finds that also Radix Puerariae have antagonism glutamic acid and causes neurocyte excitation [Acta Pharmacologica Sinica 1998,19 (4): 339～342], and puerarin preparation for eye will become a kind of good anti-glaucoma medicine.
The present invention relates to the specific gel for eye use dosage form of Chinese medicine puerarin, active component is a puerarin.Gel-type vehicle is selected carbomer, carbomer [2000 editions (two ones): P133 of pharmacopeia] is the crosslinked acrylate copolymer that forms of acrylic acid and alkyl sucrose, and carbomer is soluble in water, forms colloid, in pH value 6～10 o'clock, add inorganic or organic base can form transparent and stiff gel, to skin and mucosa avirulence and zest, and it is fast to have a release, no greasy, easily be coated with exhibition, energy and aqueous solution, physicochemical property is stable, is a kind of very ideal pharmaceutical excipient.Borax and boric acid are adopted in the pH regulator agent.Carbomer is a gel-type vehicle, Borax, boric acid and carbomer form the gel of transparent and stable, and can keep the stable of pH value, add the puerarin gel that the active component puerarin is made, splash into back and the approaching neutrality of tear combination in the eyelid, non-stimulated to eye, release is fast, can be good at being absorbed the performance drug action by ocular tissue.
The materia medica test of puerarin ophthalmic gel of the present invention:
Verify the effect of puerarin ophthalmic gel blood circulation promoting and blood stasis dispelling (the treatment retinal vein occlusion) and intraocular pressure lowering, and compare with the puerarin eye drop.
Puerarin ophthalmic gel, content are 1%, and substrate is 0.2% carbomer;
Puerarin eye drop, content are 1%;
The preparation of 1% methylcellulose: get 1g methylcellulose (production of Shanghai reagent two factories) and add among the injection ringer's solution 30ml that boils, add injection ringer's solution 70ml after the cooling again, the autoclave sterilization sterilization is standby.
Instrument Schiotz tonometer, Suzhou Medical Instruments Factory produces.
The Wistar rat, body weight 200g～300g, male and female half and half.Japan's white big ear rabbit, body weight 1.6g～2.3g, male and female half and half provide by Chinese Medical Sciences University's second clinical hospital Experimental Animal Center.
1, the thrombotic effect of Chinese People's Anti-Japanese Military and Political College Mus
Get 40 of above-mentioned Wistar kind rats, body weight 200g～300g, male and female half and half are divided into 4 groups at random, and 10 every group are promptly: blank group, the large and small dosage group of puerarin eye drop (20mg/kg) and puerarin ophthalmic gel (20mg/kg and 10mg/kg).Each organizes the equal lumbar injection barbital sodium of rat 0.05g/kg, behind the trachea interpolation polyethylene tube, separates right common carotid artery and left external jugular vein.Put into No. 4 surgical threads of a long 5cm in the stage casing of three sections polyethylene tubes.(50u/ml) is full of the polyethylene tube chamber with heparin-saline solution, after an end of pipe inserts left external jugular vein, injects heparin 50u/kg from polyethylene tube, clamps tube wall.The other end of pipe is inserted right common carotid artery.Vena femoralis injection puerarin eye drop, gel for eye use or 2% carbomer immediately after the operation.Open blood flow behind the 5min, middle Herba Clinopodii takes out silk thread rapidly and weighs behind the open blood flow 15min, and gross weight deducts silk thread and heavily promptly gets wet weight of thrombus.Be calculated as follows suppression ratio, the results are shown in Table 1.
Suppression ratio (%)=(it is heavy that the matched group thrombosis weighs an administration group thrombosis)/matched group thrombosis heavy * 100%.
The influence that table 1 pair rat suppository forms (X ± SD)
Group Dosage (mg/kg) Number of animals (n) Thrombus weight (mg) Suppression ratio (%)
Matched group eye drop gel for eye use size Deng capacity 20 20 10 10 10 10 10 22.3±2.1 13.2±2.3 ** 12.3±1.8 ** 20.2±2.6 0 40.8 44.8 9.4
Compare with matched group *P＜0.01
The result shows that puerarin ophthalmic gel and eye drop all make the rat suppository wet weight significantly alleviate, and with the normal saline group significant difference (P＜0.01) is arranged relatively.
2, stasis syndrome rat model blood is become the influence of mathematic(al) parameter
Get 40 of Wistar kind rats, male and female half and half, body weight are 270g～290g, are divided into 4 groups at random.Every group 10.Be blank group (lumbar injection 2% carbomer), puerarin eye drop group (lumbar injection puerarin eye drop 200mg/kg) and the large and small dosage group of puerarin ophthalmic gel (lumbar injection puerarin ophthalmic gel 20mg/kg and 10mg/kg), successive administration is the equal subcutaneous injection epinephrine inj of each treated animal 0.5mg/kg after 7 days, totally 2 times, 2 minor tick 4h.(each interval 2h of front and back) immerses 5min in the frozen water with rat between 2 injection adrenal gland injection.Each is organized rat and stops eating behind the 24h.Get ventral aorta blood.The sodium citrate anticoagulant is got 0.5ml and is determined at low shear rate (1.18s with rotary viscosimeter -1) and high shear rate (118s -1) under whole blood viscosity; Measure packed cell volume with capillary tube method; Measure plasma fibrinogen content with the thermal precipitation method; Get ventral aorta blood and measure plasma viscosity with capillary viscosimeter.The results are shown in Table 2.
The influence of table 2 pair hemorheology of rat parameter (X ± SD, n=10)
Group Dosage mg/kg Whole blood viscosity (mpa.sec) 118s -1 Whole blood viscosity (mpa.sec) 1.18s -1 Packed cell volume (%) Fibrinogen (%) Plasma viscosity
Blank eye drop gel for eye use size Deng capacity 20 20 10 4.53±0.41 3.94±0.36 ** 3.93±0.25 ** 4.34±0.45 10.9±1.9 11.4±2.1 11.1±1.6 12.0±2.1 45.6±8.0 38.5±5.9 * 38.8±4.4 * 45.5±6.6 4.74±0.66 4.69±0.70 4.80±0.92 4.72±0.95 2.62±0.74 1.97±0.18 * 1.98±0.28 * 2.13±0.31
Compare with the normal saline group, *P＜0.05 *P＜0.01
The result shows that the puerarin ophthalmic gel is the same with eye drop, and whole blood viscosity and packed cell volume under the high shear rate are obviously reduced, and plasma viscosity is obviously reduced.
3, to the microcirculatory influence of rabbit conjunctive bulbi
Get 40 of healthy no ophthalmic rabbit, body weight 1.6kg～2.3kg, male and female half and half are divided into 4 groups at random, 10 every group.Be model control group, puerarin eye drop (1%) and the large and small dosage group of puerarin ophthalmic gel (1% and 0.5%).Rabbit conjunctive bulbi microcirculation is observed and is adopted XS-SI microcirculation microscope (6 * 8 times), and rabbit waking state lateral position is fixed, the cold light source irradiation.Observation index:
(1) fluidised form is described, and the erythrocyte fluidised form can be divided into level Four, and standards of grading see Table 3-1.
(2) point of intersect of the capillary network computational methods are observed 1mm 2The net intersection point of zone blood capillary changes, and observes normal left eye bulbar Conjunctiva Microcirculation earlier, injects 10% high molecular dextran normal saline solution 15ml/kg from auricular vein then and causes microcirculation disturbance (be slow blood flow, hemocyte is assembled).After this phenomenon was stable, matched group dripped 2% carbomer, and administration group eye drip is given 3 (0.15ml), observed 5min, 10min after the administration, 15min, 20min and 30min microcirculation situation of change then, the results are shown in Table 3-2 and table 3-3.
The classification of table 3-1 erythrocyte fluidised form
Classification Fluidised form Score value
O I II III The granular stasis of blood of the linearity dotted line shape shape (left-falling stroke flow phenomenon) that stagnates 0 1 2 3
Table 3-2 is to the influence of the plain conjunctiva blood capillary of lagophthalmos cell fluidised form score value (X ± SD)
Group Dosage % Number of animals only Score value flows
Before the modeling Before the administration 5min after the administration 10min 15min 20min 30min
Model control group - 10 0.30±0.48 2.50±0.53 2.40±0.52 2.44±0.53 2.30±0.48 2.20±0.63 2.10±0.57
Eye drop gel for eye use size 1 1 0.5 10 10 10 0.30±0.48 0.20±0.42 0.40±0.52 2.70±0.48 2.40±0.52 2.50±0.53 2.20±0.63 1.90±0.57 2.30±0.67 1.22±0.83 ** 1.20±0.79 ** 1.10±0.74 ** 0.90± 0.88 ** 0.80± 0.63 ** 1.10±0.74 1.10±0.74 ** 0.60±0.52 ** 1.50±0.53 * 1.30±0.95 * 0.60±0.69 ** 2.00±0.67
Compare with model control group *P＜0.05 *P＜001
Table 3-3 is to the influence of lagophthalmos bulbar conjunctiva point of intersect of the capillary network (X ± SD)
Group Dosage % Number of animals only Score value flows
Before the modeling Before the administration 5min after the administration 10min 15min 20min 30min
Model control group eye drops gel for eye use size - 1 1 0.5 10 10 10 10 6.5±1.08 6.7±1.16 6.8±1.32 6.7±1.16 3.5±1.08 3.5±0.97 3.2±1.03 3.6±1.07 3.3±1.25 4.0±1.15 4.0±0.82 3.5±0.71 3.2±1.03 4.4±0.97 ** 5.0±1.15 ** 3.9±0.99 3.4±0.84 4.9±0.99 ** 5.4±1.17 ** 4.3±0.95 * 3.4±0.97 5.1±1.1 ** 5.5± 1.72 ** 4.6± 0.97 ** 3.5±0.71 5.2±1.03 * 6.4±1.35 **△ 4.6±1.07 *
Compare with model control group, *P＜0.05 *P＜0.01; Compare with the eye drop group △P＜0.05
The result shows that behind the intravenous injection high molecular dextran, microcirculation becomes the II-III level by the permanent current attitude of going down, and red small thrombosis occurs, and blood flow rate significantly slows down, and occurs individually swinging back and forth and arrheaing, and after the eye drip administration, the blood flow fluidised form is significantly improved.10min～30min behind large and small dosage group of puerarin ophthalmic gel and the eye drop group eye drip all can make blood flow recover normally (P＜0.05,0.01) substantially, and two medicine effects are suitable.But during 30min, the puerarin ophthalmic gelatification is better than eye drop (P＜0.05).
4, to the influence of the high Intraocular Pressure Model of Experimental Rabbits
Get 30 of healthy no ophthalmic rabbit, body weight 1.6kg～2.1kg, male and female half and half are divided into 5 groups at random, 6 every group (12 eyes).That is: blank group, model group, puerarin eye drop (1%) and the large and small dosage group of puerarin ophthalmic gel (1% and 0.5%) are surveyed every eye intraocular pressure 2 times earlier before the experiment, average as the normal intraocular tension value.Respectively organize rabbit then, under aseptic condition, extract the 0.2ml aqueous humor, injection 1% methylcellulose in generation or balanced salt solution 0.2ml (blank group), so modeling is 2 times, 2 days at interval.Begin the eye drip administration next day after the last modeling, every day 1 time, each 3 (0.15ml), and successive administration 7 days was surveyed each treated animal intraocular pressure value in 0.5 day, 1 day, 3 days, 7 days after the administration, and all data are carried out the t check, the results are shown in Table 4.
The influence of the high Intraocular Pressure Model of table 4 Experimental Rabbits (X ± SD)
Group Dosage % Number of animals only Intraocular pressure value (Kpa)
Normal intraocular tension After the modeling After the administration 0.5 day 1 day 3 days 5 days 7 days
Blank model control group eye drop gel for eye use size - - 1 1 0.5 12 12 12 12 12 2.49±0.08 2.52±0.05 2.49±0.01 2.50±0.02 2.50±0.01 2.50±0.09 6.84±0.23 △ 6.81±0.34 6.86±0.28 6.84±0.20 2.51±0.07 6.78±0.23 △ 6.59±0.39 6.46±0.36 * 6.66±0.31 2.50±0.07 6.24±0.26 △ 5.33±0.47 ** 5.30±0.32 ** 6.20±0.29 2.49±0.07 5.66±0.35 △ 4.11±0.49 ** 3.22±0.25 ** 5.12±0.36 ** 2.49±0.06 4.85±0.45 △ 2.9±0.24 ** 2.66±0.19 ** 3.56±0.43 ** 2.50±0.06 3.28±0.45 2.55±0.13 ** 2.50±0.10 ** 2.82±0.24 **
Compare with the blank group △P＜0.01; Compare with model group *P＜0.05 *P＜0.01
The result shows, model group and blank group comparing difference highly significant (P＜0.01) illustrate the modeling success.Large and small dosage group of puerarin ophthalmic gel and eye drop group all can reduce the lagophthalmos high-voltage value (P＜0.05,0.01) that 1% methyl fiber causes.But the puerarin ophthalmic gel is more Zao action time than eye drop.
Effect experiment is the result show, puerarin ophthalmic gel and eye drop all have the thrombotic effect of Chinese People's Anti-Japanese Military and Political College Mus, all can change stasis syndrome rat model blood rheology parameter, obviously improve the circulation of lagophthalmos bulbar conjunctiva, effect with blood circulation promoting and blood stasis dispelling is described, clinically can be used for treating the retinal vein occlusion.The result shows that simultaneously the puerarin ophthalmic gel is strong than the eye drop effect.The puerarin ophthalmic gel can obviously reduce the high intraocular pressure of rabbit that 1% methylcellulose causes, and onset time is early than eye drop.
5, puerarin ophthalmic gel acute toxicity test
The maximum tolerated dose of puerarin ophthalmic gel mouse peritoneal drug administration by injection is 0.1g/kg, be equivalent to 1667 times of clinical human eye drip daily dose, the maximum tolerated dose of mouse mainline administration is 0.05g/kg, be equivalent to 833 times of clinical human eye drip daily dose, illustrate that the clinical eye drip of product of the present invention is safe.
6, puerarin ophthalmic gel eye irritation and sensitivity test
The puerarin ophthalmic gel does not in single or divided doses all present the local excitation reaction to lagophthalmos, and damaged conjunctiva is not had the obvious stimulation reaction yet; Through the Cavia porcellus allergic experiment, do not find anaphylaxis.
Embodiment 1:
The prescription of preparation gel of the present invention: puerarin 8.0g, carbomer 2.0g, Borax 8.0g, boric acid 3.0g, water for injection adds to 1000g.
Method for making: get puerarin 8.0g with about 900ml water for injection dissolving, then gel-type vehicle carbomer 2.0g is soaked wherein 12h.Get Borax 8.0g, boric acid 3.0g and add wherein, stir, add to the full amount of water for injection, fully stir, filter, get clear gel with 220 mesh sieve cloth, pressure sterilizing, cooling, packing gets product of the present invention, and pH is 6.3.
Embodiment 2:
The prescription of preparation gel of the present invention: puerarin 15.0g, carbomer 6.0g, Borax 15.0g, boric acid 8.0g, water for injection adds to 1000g.
Method for making: get puerarin 15.0g with about 900ml water for injection dissolving, then gel-type vehicle carbomer 8.0g is soaked wherein 12h.Get Borax 15.0g, boric acid 8.0g and add wherein, stir, add to the full amount of water for injection, fully stir, filter, get clear gel with 220 mesh sieve cloth, pressure sterilizing, cooling, packing gets product of the present invention, and pH is 6.2.
Embodiment 3:
The prescription of preparation gel of the present invention: puerarin 10.0g, carbomer 4.0g, Borax 10.0g, boric acid 5.0g, water for injection adds to 1000g.
Method for making: get puerarin 10.0g with about 900ml water for injection dissolving, then gel-type vehicle carbomer 4.0g is soaked wherein 12h.Get Borax 10.0g, boric acid 5.0g and add wherein, stir, add to the full amount of water for injection, fully stir, filter, get clear gel with 220 mesh sieve cloth, pressure sterilizing, cooling, packing gets product of the present invention, and pH value is 6.3.
Embodiment 4:
The prescription of preparation gel of the present invention: puerarin 5.0g, carbomer 2.0g, Borax 5.0g, boric acid 3.0g, water for injection adds to 1000g.
Method for making: get puerarin 5.0g with about 900ml water for injection dissolving, then gel-type vehicle carbomer 2.0g is soaked wherein 12h.Get Borax 5.0g, boric acid 3.0g and add wherein, stir, add to the full amount of water for injection, fully stir, filter, get clear gel with 220 mesh sieve cloth, pressure sterilizing, cooling, packing gets product of the present invention, and pH value is 5.5.
Embodiment 5:
The prescription of preparation gel of the present invention: puerarin 20.0g, carbomer 10.0g, Borax 20.0g, boric acid 8.0g, water for injection adds to 1000g.
Method for making: get puerarin 20.0g with about 900ml water for injection dissolving, then gel-type vehicle carbomer 10.0g is soaked wherein 12h.Get Borax 20.0g, boric acid 8.0g and add wherein, stir, add to the full amount of water for injection, fully stir, filter, get clear gel with 220 mesh sieve cloth, pressure sterilizing, cooling, packing gets product of the present invention, and pH is 6.6.

Claims (3)

1, a kind of puerarin ophthalmic gel, it is characterized in that forming by puerarin, gel base material, pH regulator agent, water for injection, in 100 parts of gel weight, the weight ratio puerarin is 0.5～2.0, the gel base material is 0.1～1.0, is the pH regulator agent with Borax, boric acid, regulates pH value 5.0～7.0, all the other are water for injection, and used gel base material is a carbomer.
2, puerarin ophthalmic gel according to claim 1 is characterized in that in 100 parts of gel weight, the weight ratio puerarin is 0.8～1.5, the gel base material is 0.2～0.6, with Borax, boric acid is the pH regulator agent, regulates pH value 6.0～6.5, and all the other are water for injection.
3, the preparation method of puerarin ophthalmic gel according to claim 1 and 2, it is characterized in that: puerarin dissolves with water for injection, then gel base material carbomer is soaked wherein 12h; PH regulator agent Borax, boric acid are added wherein, stir, control pH value 5.0～7.0 adds to the full amount of water for injection, and fully stirs, and filters with 220 mesh sieve cloth, gets clear gel, pressure sterilizing, and cooling divides and puts into the storehouse.
CN 02145139 2002-11-05 2002-11-05 Puerarin gelation for eye use and prepn. method Expired - Lifetime CN1268344C (en)

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CN112972683A (en) * 2019-12-13 2021-06-18 刘力 Locally administered medicinal composition of gellinzomib and the like
CN113786380A (en) * 2021-09-18 2021-12-14 华北制药股份有限公司 Pilocarpine nitrate ophthalmic gel and preparation method thereof
CN115998943A (en) * 2022-12-20 2023-04-25 北京中医药大学 Hydrogel for promoting skin wound healing and application thereof

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