CN106727454A - Sodium paeonol sulfonate eye-drops preparations - Google Patents
Sodium paeonol sulfonate eye-drops preparations Download PDFInfo
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Abstract
The invention discloses a kind of sodium paeonol sulfonate eye-drops preparations, it is made of the addition eye-drops preparations pharmaceutic adjuvant in sodium paeonol sulfonate, and the percentage by weight of contained sodium paeonol sulfonate is 0.01 30%, balance of eye-drops preparations pharmaceutic adjuvant.Sodium paeonol sulfonate eye-drops preparations is including eye drops, ophthalmically acceptable liposome, inclusion compound eye drops, eye ointment, gel for eye use, in-situ gel, ophthalmically acceptable liposome gel, ophthalmically acceptable injection, ophthalmically acceptable lipidosome injection etc..The present invention is made of with sodium paeonol sulfonate as active ingredients, adds eye-drops preparations pharmaceutic adjuvant routinely preparation method.Sodium paeonol sulfonate is made ophthalmic remedy, effective absorption for increased medicine, the stability that improve medicine, extend the eye holdup time, the toxic and side effect for reducing medicine, the eye bioavilability that improves medicine.It is preparation method feasible process of the invention, quality controllable, there is boundless industrialization prospect.
Description
Technical field
The present invention relates to the medicine of ophthalmology disease, more particularly, to a kind of sodium paeonol sulfonate eye-drops preparations.
Background technology
Root bark of tree peony sulfocarbolate is widely used in the aspects such as treatment postoperative pain, rheumatism, rheumatoid and fresh preservation,
Clinically have a wide range of applications.Presently commercially available formulation is sodium paeonol sulfonate injection, has no and prepared with sodium paeonol sulfonate
The application of ophthalmic preparations and report.
Chinese patent CN102166205B discloses the medical usage of Paeonol and its derivative, shows sodium paeonol sulfonate
Effect with treatment or epidemic prevention membranous conjunctivitis, dry eyes, uveitis and sclerotitis.United States Patent (USP) US2008/
0194700A1 discloses Paeonol or a pharmaceutically acceptable salt can be used to prevent, improve or treat and Angiogenesis
Disease, such as neovascular glaucoma, diabetic retinopathy, because of disease of cornea, macular degeneration, wing caused by angiogenesis
The illness in eye such as the triangular mass of mucous membrane growing from the inner corner of the eye, retinosis, the cure mechanism of its description is to suppress angiogenesis.
In addition, sodium paeonol sulfonate has the erythrocyte hemolysis of the active and anti-UV inductions of stronger scavenging activated oxygen
Effect, also has stronger inhibitory action to some plant pathogenetic bacterias and fungi etc..Its effect to fresh preservation is just from pellet
Skin natrium phenolsulfonicum protects the effect of superoxide dismutase, removing free radical closely related.Research finds that cataract is the first world
Position blinding factor, while being also the primary diseases causing blindness of China.Cataract occur evolution degree in, free radical and with
Its related oxidative stress is the hinge for causing crystalline lens physiological function to change, ultimately result in cataract.Therefore, root bark of tree peony phenol sulfonic acid
Sodium is expected to produce certain pharmacological action to the generation development of cataract.
In view of the notable eye pharmacological action of above sodium paeonol sulfonate, only injection formulation is present at present, and exploitation is red
The ophthalmic preparations of skin natrium phenolsulfonicum need to solve problems with：Improve stability, the enhancing root bark of tree peony phenol sulfonic acid of sodium paeonol sulfonate
The cornea and conjunctiva permeability of sodium, the eye holdup time of extension sodium paeonol sulfonate, the eye life of raising sodium paeonol sulfonate
Thing availability.
The content of the invention
It is an object of the invention to provide a kind of new preparation variety of sodium paeonol sulfonate, the i.e. ophthalmically acceptable system of sodium paeonol sulfonate
Agent, the sodium paeonol sulfonate eye-drops preparations increased medicine effective absorption, improve the stability of medicine, to extend eye stagnant
The time is stayed, the toxic and side effect of medicine is reduced, is improve the eye bioavilability of medicine.
The object of the present invention is achieved like this：
A kind of sodium paeonol sulfonate eye-drops preparations, be characterized in：Eye-drops preparations pharmaceutic adjuvant is added in sodium paeonol sulfonate
It is made, the percentage by weight of contained sodium paeonol sulfonate is 0.01-30%, balance of eye-drops preparations pharmaceutic adjuvant.
Sodium paeonol sulfonate eye-drops preparations of the invention includes sodium paeonol sulfonate eye drops, sodium paeonol sulfonate liposome
Eye drops, sodium paeonol sulfonate inclusion compound eye drops, sodium paeonol sulfonate eye ointment, sodium paeonol sulfonate gel for eye use, Paeonol
The ophthalmically acceptable liposome gel of sodium sulfonate in-situ gel, sodium paeonol sulfonate, the ophthalmically acceptable injection of sodium paeonol sulfonate, Paeonol sulphur
The sour ophthalmically acceptable lipidosome injection of sodium, the composition of above-mentioned various preparations is as follows：
1st, a kind of sodium paeonol sulfonate eye drops, is made up of the raw material of following percentages：
2nd, a kind of sodium paeonol sulfonate liposome eye drops, is made up of the raw material of following percentages：
3rd, a kind of sodium paeonol sulfonate inclusion compound eye drops, is made up of the raw material of following percentages：
4th, a kind of sodium paeonol sulfonate eye ointment, is made up of the raw material of following percentages：
5th, a kind of sodium paeonol sulfonate gel for eye use, is made up of the raw material of following percentages：
6th, a kind of sodium paeonol sulfonate in-situ gel, is made up of the raw material of following percentages：、
7th, a kind of sodium paeonol sulfonate liposome gel, is made up of the raw material of following percentages：
8th, the ophthalmically acceptable injection of a kind of sodium paeonol sulfonate, is made up of the raw material of following percentages：
9th, the ophthalmically acceptable lipidosome injection of a kind of sodium paeonol sulfonate, is made up of the raw material of following percentages：
The pH adjusting agent be NaOH, HCl, citric acid, triethanolamine, trishydroxymethylaminomethane, boric acid, Boratex,
One or more in acetic acid and sodium acetate, sodium carbonate, sodium acid carbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate.
The pH value is 3.0-10.0.
The NMF be glycerine, Sodium Hyaluronate in one or two.
The isotonic regulator is sodium chloride, glycerine, glucose, sodium carbonate, sodium acid carbonate, disodium hydrogen phosphate, di(2-ethylhexyl)phosphate
One or more in hydrogen sodium, boric acid, borax, mannitol and propane diols.
The preservative is thimerosal, sorbic acid, phenylmercuric acetate, BZK, benzalkonium bromide, Sodium Benzoate, benzene oxygen second
One or more in alcohol, methyl hydroxybenzoate, ethylparaben, propylben and anesin.
The antioxidant is sodium sulfite, sodium hydrogensulfite, sodium pyrosulfite, sodium thiosulfate, thiocarbamide, vitamin E, dimension
One or more in raw element A, vitamin C and carrotene.
The metal-chelator be ethylenediamine tetra-acetic acid (Ethylene Diamine Tetraacetic Acid, EDTA),
One or more in EDTA-2Na, EDTA-Ca and EDTA-2K.
The eye pasting substrate is one or more of fatty alcohol, yellow petroleum jelly, albolene, lanolin and atoleine.
The liposome materials are phosphatidylcholine class, phosphatidyl glycerol class, phosphatidyl-4 alcohols, phosphatidyl-ethanolamine
Class, sphingomyelin class, single-stranded or double-stranded phosphatide (two nutmegs acid phosphatidyl glycerol, tin dilaurate phosphatidyl glycerol, two palmitic acid
Phosphatidyl glycerol, DSPG, two nutmegs acid phosphatidic acid, tin dilaurate phosphatidic acid, two palmitic acid phosphatidic acids, two
Stearic acid phosphatidic acid, two oleic acid phosphatidylserines, dilinoleic acid phosphatidylinositols, DPPC (DPPC),
Tin dilaurate phosphatid ylcholine (DLPC), two myristic acid phosphatid ylcholines (DMPC), DSPC (DSPC),
Single nutmeg acid phosphatidyl glycerol, mono laurate phosphatidyl glycerol, single palmitic acid phosphatidyl glycerol, monostearate phosphatidyl glycerol,
Single nutmeg acid phosphatidic acid, mono laurate phosphatidic acid, single palmitic acid phosphatidic acid, monostearate phosphatidic acid, single oleic acid phosphatidyl silk ammonia
Acid, single linoleic acid phosphatidylinositols, single palmitic acid phosphatid ylcholine (MPPC), mono laurate phosphatid ylcholine (MLPC), single meat
One or more in myristic acid phosphatid ylcholine (MMPC), MSPC (MSPC).
The covering material be polyethylene glycol 2000, Macrogol 4000, Macrogol 6000, polyvinyl alcohol, cyclodextrin,
One or more in shitosan, chitosan oligosaccharide, carboxymethyl chitosan, trimethyl chitin.
The gel-type vehicle is the macromolecular material with pH value, temperature or ion-sensitive characteristic, selected from Carbomer, ties cold
Glue, sodium alginate, melon glue, pectic substance, polyethylene glycol, poloxamer, sodium hyaluronate, Hydroxypropyl methylcellulose (HPMC), methyl
One or more in cellulose (MC), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA).
Inclusion compound material in the sodium paeonol sulfonate inclusion compound eye drops is cyclodextrin, beta-schardinger dextrin, hydroxy propyl-Beta-
One or more in cyclodextrin.
The present invention is with sodium paeonol sulfonate as active ingredients, adds eye-drops preparations pharmaceutic adjuvant routinely preparation method
It is made.Sodium paeonol sulfonate is made ophthalmic remedy, increased effective absorption of medicine, improves the stability of medicine, extends
Eye holdup time, the toxic and side effect for reducing medicine, the eye bioavilability that improve medicine.Preparation method of the invention
It is feasible process, quality controllable, there is boundless industrialization prospect.
Specific embodiment
For a better understanding of the present invention, it is with reference to the embodiment content that the present invention is furture elucidated but of the invention
Content is not limited solely to the following examples.
Embodiment 1：Sodium paeonol sulfonate eye drops
Water for injection 50mL is taken, NaCl 0.7g, boric acid 1.9g, sodium hydrogensulfite 0.2g, EDTA-2Na0.03g, benzene is added
Prick oronain 0.03g, Sodium Hyaluronate 0.1g, be stirred to dissolve, add sodium paeonol sulfonate 3.5g, it is to be dissolved completely after, plus
Enter water for injection to 100mL, with citron acid for adjusting pH to 6.0.0.22 μm of filtering with microporous membrane, it is aseptic subpackaged in brown plastics drop
In eye bottle, packaging is obtained final product.
Embodiment 2：Sodium paeonol sulfonate liposome eye drops
Using film dispersion method, take soybean lecithin 1g, cholesterol 0.75g and be dissolved in chloroform as oil phase, use rotation
55 DEG C of evaporimeter is evaporated film forming, removes chloroform, and holding vacuum of stopping the rotation continues to stop after aspirating 2h, and addition contains sodium sulfite
(pH in the phosphate buffer 50mL of 0.15g, EDTA-2Na 0.03g, benzalkonium bromide 0.02g and sodium paeonol sulfonate 0.2g
6.0) 40min, is acutely shaken, washes after film that high pressure homogenizer homogenizes (homogenization pressure 80Mpa, cycle-index 5 under the conditions of 4 DEG C
It is secondary), obtain final product sodium paeonol sulfonate liposome eye drops.Obtained sodium paeonol sulfonate liposome eye drops are slowly dropped into shell few
In phosphate buffer (1%, the w/v) 50ml of sugared (50kDa), 10 DEG C stir and evenly mix 60min, obtain final product chitosan oligosaccharide cladding Paeonol
Sodium sulfonate liposome turbid liquor, is adjusted to isotonic using NaCl, with citron acid for adjusting pH to 7.4, determines envelop rate>49.8%.
0.22 μm of filtering with microporous membrane, nitrogen charging, aseptic subpackaged in brown plastic bottles, packaging is obtained final product.
Embodiment 3：Sodium paeonol sulfonate inclusion compound eye drops
HP- beta-schardinger dextrin 1g are taken, water for injection 75mL is added, heating makes dissolving, add sodium paeonol sulfonate 0.1g, stirring
Make dissolving, put ultrasonator ultrasound 10min, sequentially add sodium chloride 0.6g, boric acid 0.4g, borax 1.3g, Metagin
Ester 0.1g, propylben 0.02g, EDTA-2K 0.04g, sodium hydrogensulfite 0.1g are stirred to dissolve, with HCl adjust pH to
6.5.0.22 μm of filtering with microporous membrane, aseptic subpackaged in brown plastic bottles, packaging is obtained final product.
Embodiment 4：Sodium paeonol sulfonate eye ointment
Eye pasting substrate：Albolene 50g, atoleine 10g, wool grease 10g are taken, 150 DEG C of fusings, stirring are heated to
Uniformly, vitamin E 0.5g, carrotene 1.5g are added, is cooled down standby.Water for injection 20mL is taken, sodium sulfite 0.2g is added,
EDTA 0.05g, vitamin C 0.2g, anesin 0.02g, are stirred to dissolve, and add sodium paeonol sulfonate 6.0g, obtain
It is standby to the sodium paeonol sulfonate aqueous solution.Take above-mentioned eye pasting substrate and be ground into fine and smooth pasty state with the sodium paeonol sulfonate aqueous solution, then divide
Secondary incremental eye pasting substrate to total amount 100g, packing, packaging is obtained final product.
Embodiment 5：Sodium paeonol sulfonate gel for eye use
Sodium chloride 0.9g, boric acid 1.9g, sodium sulfite 0.2g, EDTA-2Na 0.03g are taken, is stirred to dissolve in injection
Water 100mL, adds sodium paeonol sulfonate 3g, it is to be dissolved completely after, add HPMC K4M 1.2 and ethylparaben 0.03g,
Heating, stirring and dissolving is stood overnight to room temperature, and pH to 7.0 is adjusted with HCl.0.22 μm of filtering with microporous membrane, checks that clarity is closed
After lattice, nitrogen charging, aseptic subpackaged in brown plastic bottles, packaging is obtained final product.
Embodiment 6：Sodium paeonol sulfonate gel for eye use
Water for injection about 60mL is taken, Phenoxyethanol 0.3g is added, heating stirring makes dissolving, be heated to 80 DEG C, add hydroxypropyl
Methylcellulose HPMC K4M 1.5g, stir, and add 2g sodium paeonol sulfonates, EDTA0.04g, vitamin C 0.1g,
Stirring makes to form clear solution, filters, and by several times adds 0.2g Acritamer 940s, stirring while adding swelling to being completely dispersed, and adds
Water for injection 40mL, adds 0.1M NaOH to adjust pH to 7.5,0.22 μm of filtering with microporous membrane, after checking that clarity is qualified,
Nitrogen charging, aseptic subpackaged in brown plastic bottles, packaging is obtained final product.
Embodiment 7：Sodium paeonol sulfonate in-situ gel
Water for injection about 70mL is taken, benzalkonium chloride 0.005g is added, heating stirring makes dissolving, adds 2g root bark of tree peony phenol sulfonic acids
Sodium, sodium hydrogensulfite 0.1g, EDTA-2K 0.03g, vitamin C 0.1g, stirring makes to form clear solution, adds poloxamer
P188 7g, stirring and dissolving, adds F127 21g at room temperature, after dispersed with stirring is uniform, is refrigerated into 4 DEG C of refrigerators
More than 48h, obtains clear solution, and moisturizing causes into 100mL.
Embodiment 8：Sodium paeonol sulfonate liposome gel
Using film dispersion method, egg yolk lecithin 3g, cholesterol 0.8g, vitamin E 0.6g, retinol1 .5g are taken, it is molten
As oil phase in chloroform, using Rotary Evaporators, 60 DEG C are evaporated film forming, remove chloroform, and holding vacuum of stopping the rotation continues to aspirate
Stop after 2h, add (pH in the phosphate buffer 50mL containing EDTA-2Na 0.03g and sodium paeonol sulfonate 0.6g
6.8) 40min, is acutely shaken, washes after film that high pressure homogenizer homogenizes (homogenization pressure 80Mpa, cycle-index 5 under the conditions of 4 DEG C
It is secondary), obtain final product sodium paeonol sulfonate liposome turbid liquor.Prepared sodium paeonol sulfonate liposome turbid liquor is slowly dropped into trimethyl
In phosphate buffer (1%, w/v) 50ml of shitosan, 10 DEG C stir and evenly mix 60min, are adjusted to isotonic using NaCl, obtain final product
Trimethyl chitin coats sodium paeonol sulfonate liposome turbid liquor.HPMC K4M 1.5g and ethylparaben 0.03g are scattered in
In the water for injection of 50mL, heating, stirring and dissolving stands overnight to room temperature, obtains HPMC solution.Trimethyl chitin is coated
Sodium paeonol sulfonate liposome turbid liquor mixes with HPMC solution, is quantified with the water for injection of filtration sterilization, filling to obtain final product.
Embodiment 9：The ophthalmically acceptable injection of sodium paeonol sulfonate
Water for injection 50mL is taken, sodium chloride 0.9g, sodium sulfite 0.2g, EDTA-2K 0.03g, benzalkonium chloride is added
0.03g, is stirred to dissolve, and adds sodium paeonol sulfonate 2g, it is to be dissolved completely after, add water for injection to 100mL, use citron
Acid for adjusting pH is to 6.5.0.22 μm of filtering with microporous membrane, after checking that clarity is qualified, nitrogen charging is aseptic subpackaged in brown ampoule,
Packaging is obtained final product.
Embodiment 10：Sodium paeonol sulfonate lipidosome injection
Using film dispersion method, take soybean lecithin 1g, cholesterol 0.75g and be dissolved in chloroform as oil phase, use rotation
55 DEG C of evaporimeter is evaporated film forming, removes chloroform, and holding vacuum of stopping the rotation continues to stop after aspirating 2h, and addition contains pyrosulfurous acid
(pH in the phosphate buffer 50mL of sodium 0.25g, EDTA-2Na 0.03g, methyl hydroxybenzoate 0.03g and sodium paeonol sulfonate 4g
6.0) 40min, is acutely shaken, washes after film that high pressure homogenizer homogenizes (homogenization pressure 80Mpa, cycle-index 5 under the conditions of 4 DEG C
It is secondary), adjusted to isotonic using NaCl, adjust pH to 7.5.0.22 μm of filtering with microporous membrane, after checking that clarity is qualified, nitrogen charging,
It is aseptic subpackaged in brown ampoule, packaging is obtained final product.
Beneficial effects of the present invention are proved below by way of experimental example.
Assay：
Instrument：High performance liquid chromatograph Waters e2695；
Chromatographic column：Inertsil ODS-3 posts (150 × 4.6mm, 5 μm)；
Column temperature：35℃；
Mobile phase：0.12% ammonium dihydrogen phosphate-acetonitrile-methanol (82: 10: 8, pH 3.5 is adjusted to phosphoric acid)；
Flow velocity：1.0ml/min；
Detection wavelength：274nm；
Sample size：20 μ l sample preparations：Sodium paeonol sulfonate sample is taken with methanol dilution suitable multiple, efficient liquid phase is injected
Particle diameter and distribution are measured in chromatograph；
Particle diameter and measure of spread；
Instrument：Malvern ZS90；
Sample preparation：Take sodium paeonol sulfonate preparation and suitable multiple is diluted with ultra-pure water, particle diameter is measured in injection particle size analyzer
And distribution.
The quality evaluation of the sodium paeonol sulfonate gel for eye use of experimental example 1
0.5g carbomer 934s are soaked through glycerine, are added HPMC K4M 0.5g and are taken water for injection about 60mL, and normal temperature is put
24h is put, makes it fully swelling, add 2g sodium paeonol sulfonates, sodium pyrosulfite 0.1g, EDTA-2Na 0.04g, stirring makes
Clear solution is formed, it is swelling to being completely dispersed, water for injection 40mL is added, add 0.1M NaOH regulation pH to 7.0,0.22
μm filtering with microporous membrane, after checking that clarity is qualified, nitrogen charging, aseptic subpackaged in brown plastic bottles, packaging is obtained final product.
1. appearance character
The prepared sodium paeonol sulfonate gel for eye use of this law is transparent, uniform and smooth.
2. viscosity measurement
Three batches of gel viscositys are determined using rotational viscometer (Anton Paar companies), 1 is the results are shown in Table, meets ophthalmically acceptable solidifying
The requirement of jelly.
Gel is (40 before and after tear dilution under the normal temperature of table 1：7, v/v) viscosity
3. dewatering ability
Each 3g of different batches sample being taken respectively, being placed in 10ml centrifuge tubes, 30min, gel gas is centrifuged through 4000rpm
Bubble is removed, and without layering, precipitation, precipitation phenomenon, proterties is transparent, uniform, illustrates that the gel stability is good.
4.HPLC method assays
Gel 0.1g is taken, the μ l of saturation NaCl solution 50 are added, stirred, flowing phase dilution constant volume, 0.22 μm of membrane filtration,
Subsequent filtrate is taken, by above-mentioned chromatographic condition, sample size is calculated, 2 are the results are shown in Table.
The sample size measurement result of table 2
The anti-cataract drug effect of experimental example 2 is tested
1 experiment material, reagent, instrument
Test medicine sodium paeonol sulfonate gel, sodium paeonol sulfonate eye drops, physiological saline；
The age in days rat of experimental animal 11；
Laboratory apparatus：UV-2550 is ultraviolet/visible spectrophotometer (Japanese Shimadzu Corporation), 3-18K high-speed refrigerated centrifuges
(German Sigma companies).
2 statistical methods
Statistical analysis is carried out with the softwares of SPSS 17.0.Data are with mean ± standard deviationRepresent, Dan Yin is used between group
LSD inspections are carried out between plain variance analysis, the neat person's group of variance, heterogeneity of variance person carries out Tamhane ' s T2 inspections.
3 experimental animals are grouped and prepared by model
Take 11 age in days rats and be grouped as follows 4 groups, every group 6 at random：Blank group, model group, sodium paeonol sulfonate eye drops
Group, sodium paeonol sulfonate gel for eye group, wherein blank group and model group gives physiological saline.Dosage regimen is administration daily
4 times, continued administration 8d.In addition to blank group, each group animal is sub- in rat collare dorsal sc injection in 30min after first administration
Sodium selenate normal saline solution (19 μm of olkg-1) formed with inducing rat cataract.After administration terminates, rat lens are taken,
Be homogenized with 10 times of amount physiological saline tissues, determine crystalline lens total number born (SOD) vigor, MDA (MDA) content,
Glutathione (GSH) content.
4 experimental results
Each experimental group biochemical indicator of table 3
| Experimental group | SOD vigor (U/mg protein) | MDA(nmol/ml) | GSH(mg/g protein) |
| Blank group | 63.5±12.3 | 2.1±0.9 | 38.7±12.6 |
| Model group | 20.1±9.80 | 15.7±3.3 | 13.6±1.5 |
| Eye drops group | 45.7±11.8* | 7.8±1.1* | 22.9±13.4* |
| Glucosamine gel group | 51.9±15.4*# | 4.4±1.2*# | 29.8±15.3* |
*：P<0.05vs. model groups；#：P<0.05vs. eye drops groups.
The anti-immune conjunctivitis effect experiment of experimental example 3
1 experiment material, reagent, instrument
Test medicine sodium paeonol sulfonate liposome eye drops, sodium paeonol sulfonate eye drops, sodium paeonol sulfonate are ophthalmically acceptable
Glucosamine gel group, physiological saline；
Experimental animal Balb/C mouse；
Laboratory apparatus：ELIASA (Bio-Rad companies of the U.S.), 3-18K high-speed refrigerated centrifuges (German Sigma companies).
2 statistical methods
Statistical analysis is carried out with the softwares of SPSS 17.0.Data are with mean ± standard deviationRepresent, Dan Yin is used between group
LSD inspections are carried out between plain variance analysis, the neat person's group of variance, heterogeneity of variance person carries out Tamhane ' s T2 inspections.
3 experimental animals are grouped and prepared by model
Take mouse and be grouped as follows 4 groups, every group 6 at random：Blank group, model group, sodium paeonol sulfonate eye drops group, the root bark of tree peony
Natrium phenolsulfonicum liposome eye drops group, sodium paeonol sulfonate gel for eye group, wherein blank group and model group give physiology salt
Water.Sensitisation phase uses the ALUM solution 0.25ml of sensibiligen chicken ovalbumin OVA, and dosage regimen is 1 times a week, to be administered continuously
2 weeks.After immune stimulating (OVA 5mg/ml), then the 5d that is administered continuously, after administration terminates, eye socket takes blood, is surveyed using ELISA method
Determine IL-4, OVA-sIgE, the content of IFN-γ in serum.
4 experimental results
Each experimental group serum measurement result of table 4
| Experimental group | IL-4(pg/ml) | OVA-sIgE(μg/ml) | IFN-γ(ng/ml) |
| Blank group | 68.7±11.0* | 0.99±0.12* | 1578.6±15.6* |
| Model group | 198.3±12.3 | 1.45±0.10 | 1130.3±36.5 |
| Eye drops group | 106.4±23.5* | 1.14±0.13* | 1346.5±26.8* |
| Liposome eye drops group | 75.8±16.1*# | 1.17±0.14* | 1499.5±25.1*# |
| Gel group | 80.7±11.2* | 1.00±0.11*# | 1398.1±23.4* |
*：P<0.05vs. model groups；#：P<0.05vs. eye drops groups.
The anti-conjunctivitis effect experiment of experimental example 4
1 experiment material, reagent, instrument
Test medicine sodium paeonol sulfonate eye ointment, sodium paeonol sulfonate situ-gel, physiological saline；
Experimental animal healthy adult large ear rabbit；
Laboratory apparatus：Handheld slit lamp (Suzhou Kang Jie companies)；
2 experimental animals are grouped and prepared by model
Set up chronic conjunctivitis model：Animal subject general anesthesia is after under row bulbar conjunctiva at top bulbar conjunctiva elongation film edge 2mm
Art of sunkening cord (scope:180 ° of top), the end of a thread does not expose.Take rabbit and be grouped as follows 4 groups, every group 6 at random：Blank group, model group,
Sodium paeonol sulfonate eye ointment, wherein sodium paeonol sulfonate situ-gel, blank group and model group give physiological saline.Dosage regimen
To be administered three times a day, it is administered continuously 5 weeks.Double-blind study observation, daily torch naked eyes and fluorescent staining slit lamp observation, record, system
One record form, quantifies score.After result display treatment 1.5 weeks, each group sign has been alleviated in addition to model group, under comprehensive scores
Drop.Medication 2-4 weeks, each group is clearly better in addition to model group, and model group still has obvious papebral conjunctiva congested.5 weeks each groups of medication are basic
Recover normal, model group still has mild hyperaemia after stimulating.Each preparation group of Paeonol is without significant stimulation and bad anti-in observation period
Should.
Claims (11)
1. a kind of sodium paeonol sulfonate eye-drops preparations, it is characterised in that：Add eye-drops preparations medicinal auxiliary in sodium paeonol sulfonate
Material is made, and the percentage by weight of contained sodium paeonol sulfonate is 0.01-30%, balance of eye-drops preparations pharmaceutic adjuvant.
2. sodium paeonol sulfonate eye-drops preparations according to claim 1, it is characterised in that：Sodium paeonol sulfonate eye-drops preparations
Including sodium paeonol sulfonate eye drops, sodium paeonol sulfonate liposome eye drops, sodium paeonol sulfonate inclusion compound eye drops, the root bark of tree peony
Natrium phenolsulfonicum eye ointment, sodium paeonol sulfonate gel for eye use, sodium paeonol sulfonate in-situ gel, the ophthalmically acceptable lipid of sodium paeonol sulfonate
The ophthalmically acceptable injection of body gel, sodium paeonol sulfonate, the ophthalmically acceptable lipidosome injection of sodium paeonol sulfonate.
3. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate is ophthalmically acceptable
Preparation is sodium paeonol sulfonate eye drops, and sodium paeonol sulfonate eye drops is made up of the raw material of following percentages：
Sodium paeonol sulfonate 0.01-30
PH adjusting agent 0.1-15
Isotonic regulator 0.2-10
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
NMF 0.1-0.3
Water for injection surplus.
4. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate is ophthalmically acceptable
Preparation be sodium paeonol sulfonate liposome eye drops, sodium paeonol sulfonate liposome eye drops by following percentages raw material group
Into：
Sodium paeonol sulfonate 0.01-30
PH adjusting agent 0.1-15
Isotonic regulator 0.2-10
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Liposome materials 0.5-40
Covering material 0.1-5
Water for injection surplus.
5. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate is ophthalmically acceptable
Preparation be sodium paeonol sulfonate inclusion compound eye drops, sodium paeonol sulfonate inclusion compound eye drops by following percentages raw material group
Into：
Sodium paeonol sulfonate 0.01-30
PH adjusting agent 0.1-15
Isotonic regulator 0.2-10
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Inclusion material 0.1-30
Water for injection surplus.
6. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate is ophthalmically acceptable
Preparation is sodium paeonol sulfonate eye ointment, and sodium paeonol sulfonate eye ointment is made up of the raw material of following percentages：
Sodium paeonol sulfonate 0.01-30
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Eye pasting substrate surplus.
7. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate is ophthalmically acceptable
Preparation is sodium paeonol sulfonate gel for eye use, and sodium paeonol sulfonate gel for eye use is made up of the raw material of following percentages：
Sodium paeonol sulfonate 0.01-30
Gel-type vehicle 0.2-20
PH adjusting agent 0.1-15
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Water for injection surplus.
8. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate is ophthalmically acceptable
Preparation is sodium paeonol sulfonate in-situ gel, and sodium paeonol sulfonate in-situ gel is made up of the raw material of following percentages：、
Sodium paeonol sulfonate 0.01-30
PH adjusting agent 0.1-15
Isotonic regulator 0.2-10
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Gel-type vehicle 0.2-50
Water for injection surplus.
9. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate is ophthalmically acceptable
Preparation be sodium paeonol sulfonate liposome gel, sodium paeonol sulfonate liposome gel by following percentages raw material group
Into：
Sodium paeonol sulfonate 0.01-30
PH adjusting agent 0.1-15
Isotonic regulator 0.2-10
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Liposome materials 0.5-40
Covering material 0.1-5
Gel-type vehicle 0.2-50
Water for injection surplus.
10. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate eye
Be sodium paeonol sulfonate liposome gel with preparation, sodium paeonol sulfonate liposome gel by following percentages raw material
Composition：
Sodium paeonol sulfonate 0.01-30
PH adjusting agent 0.1-15
Isotonic regulator 0.2-10
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Water for injection surplus.
11. sodium paeonol sulfonate eye-drops preparations according to claim 2, it is characterised in that：The sodium paeonol sulfonate eye
It is the ophthalmically acceptable lipidosome injection of sodium paeonol sulfonate with preparation, the ophthalmically acceptable lipidosome injection of sodium paeonol sulfonate is by following percentage
The raw material composition of meter：
Sodium paeonol sulfonate 0.01-30
PH adjusting agent 0.1-15
Isotonic regulator 0.2-10
Preservative 0.02-1
Antioxidant 0.01-5
Metal-chelator 0.001-0.1
Liposome materials 0.5-40
Covering material 0.1-5
Water for injection surplus.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611138866.4A CN106727454A (en) | 2016-12-12 | 2016-12-12 | Sodium paeonol sulfonate eye-drops preparations |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611138866.4A CN106727454A (en) | 2016-12-12 | 2016-12-12 | Sodium paeonol sulfonate eye-drops preparations |
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| CN106727454A true CN106727454A (en) | 2017-05-31 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107157923A (en) * | 2017-07-03 | 2017-09-15 | 武汉瑞福宁科技有限公司 | A kind of zoopery protection eye ointment and its application device |
| CN110755417A (en) * | 2019-11-27 | 2020-02-07 | 菏泽学院 | Application of paeonol in preparing medicament for resisting red blood cell hemolysis and preparation prepared from paeonol |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080194700A1 (en) * | 2005-05-06 | 2008-08-14 | Angiolab, Inc. | Use of Paeonol For Inhibiting Angiogenesis or For Enhancing Radiosensitization |
| CN101491532A (en) * | 2008-01-21 | 2009-07-29 | 昆明振华制药厂有限公司 | Erigeron breviscapus eye-preparation and preparation method thereof |
| CN102166205A (en) * | 2010-02-26 | 2011-08-31 | 张筱梅 | New medical application of paeonol and derivatives thereof |
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2016
- 2016-12-12 CN CN201611138866.4A patent/CN106727454A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080194700A1 (en) * | 2005-05-06 | 2008-08-14 | Angiolab, Inc. | Use of Paeonol For Inhibiting Angiogenesis or For Enhancing Radiosensitization |
| CN101491532A (en) * | 2008-01-21 | 2009-07-29 | 昆明振华制药厂有限公司 | Erigeron breviscapus eye-preparation and preparation method thereof |
| CN102166205A (en) * | 2010-02-26 | 2011-08-31 | 张筱梅 | New medical application of paeonol and derivatives thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107157923A (en) * | 2017-07-03 | 2017-09-15 | 武汉瑞福宁科技有限公司 | A kind of zoopery protection eye ointment and its application device |
| CN110755417A (en) * | 2019-11-27 | 2020-02-07 | 菏泽学院 | Application of paeonol in preparing medicament for resisting red blood cell hemolysis and preparation prepared from paeonol |
| CN110755417B (en) * | 2019-11-27 | 2022-12-09 | 菏泽学院 | Application of paeonol in preparing medicine for resisting erythrocyte hemolysis and preparation prepared by using paeonol |
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