CN1813843A - Eye medicinal composition for treating acute-chronic conjunctivitis and its preparing method - Google Patents
Eye medicinal composition for treating acute-chronic conjunctivitis and its preparing method Download PDFInfo
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- CN1813843A CN1813843A CN 200510020285 CN200510020285A CN1813843A CN 1813843 A CN1813843 A CN 1813843A CN 200510020285 CN200510020285 CN 200510020285 CN 200510020285 A CN200510020285 A CN 200510020285A CN 1813843 A CN1813843 A CN 1813843A
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Abstract
The present invention relates to an eye medicine composition for curing acute and chronic conjunctivitis and its preparation method. It is an eye preparation made up by using extract of chrysanthemum indicum.L. as active component and adding auxiliary materials through a certain preparation process. Besides, said invention also provides the concrete steps of its preparation method.
Description
Technical field
The present invention relates to a kind of medical composite for eye for the treatment of acute and chronic conjunctivitis and preparation method thereof, particularly, is to be medical composite for eye of forming of feedstock production and preparation method thereof with the Chinese crude drug Flos Chrysanthemi Indici, belongs to drug world.
Background technology
Conjunctivitis is the frequently-occurring disease of ophthalmology, accounts for the first place of conjunctiva disease.Its cause of disease is nothing more than microorganism and non-microorganism two big classes.With regard to microorganism, antibacterial, virus, parasite etc. all can cause the conjunctiva inflammation, and the source is very extensive, can directly come from the outside, also can be from self, and autoinfection may be transferred to conjunctiva (tuberculosis etc.) by blood flow or lymph fluid; Or by adjacent tissue, as eyeball itself (cornea, sclera), eye socket, nasal cavity and paranasal sinus, lacrimal apparatus, on every side eyelid skin direct extension.With regard to the non-microorganism cause of disease, (heat, radiation) machinery, physics, chemistry, all can become paathogenic factor down to systemic anaphylaxis state and some general metabolism sexual disorders (as rheumatism, gout).In a word, the cause of disease of conjunctivitis is extremely complicated, therefore, general current conjunctivitis clinical classification also is diversified, what have classifies (as anaphylaxis conjunctivitis) from the cause of disease, and what have then classifies with clinical manifestation, and, course of disease length suddenly slow by onset can have acute and chronic branch again.The different causes of disease can have same clinical manifestation (all can cause chronic catarrhal conjunctivitis as the various causes of disease) sometimes, or the same cause of disease can cause again that sometimes different clinical symptoms is (during as the hemolytic infection of staphylococcus aureus, can show as acute catarrhal conjunctivitis or pseudomembranous conjunctivitis), owing to above-mentioned many reasons, this just determines that the clinical manifestation of conjunctivitis usually is varied, complicated.Primary disease belongs to categories such as the traditional Chinese medical science " blood-shot eye illness ", " acute catarrhal conjunctivitis ", " acute and chronic conjunctivitis ", " swelling pain in the order ".
The medicine of treatment conjunctivitis is mainly antimicrobial drug at present, yet the side effect of antimicrobial drug is very big, can cause aplastic anemia and grey baby's syndrome as chloromycetin; Erythromycin has very intensive gastrointestinal reaction etc.And life-time service easily produces drug resistance.
Flos Chrysanthemi Indici is dry capitulum or the herb of feverfew Herba Dendranthematis indici Chrysnathemum indicum.Bitter in the mouth, cold nature, return lung, Liver Channel.Effect with heat-clearing and toxic substances removing cures mainly diseases such as carbuncle furuncle furuncle, scrofula, ophthalmalgia.Pharmacological research: staphylococcus aureus, tulase and bacill calmette-guerin, escherichia coli, dysentery bacterium, bacillus pyocyaneus are all had tangible bacteriostasis, and water preparation injects rat vein, and the inductive platelet aggregation of ADP is had the obvious suppression effect.Clinical effect: hyperlipemia, acute bronchitis, the tuberculosis of cervical lymph nodes, mumps, oral ulcer, bacillary dysentery, enteritis, prostatitis, pelvic inflammatory disease, anal sinusitis, anal papillitis etc. are all had good efficacy.(see: Liu Guoying, the pharmacological research of Flos Chrysanthemi Indici and Clinical advances, Shandong journal of Chinese medicine, 1990,9 (6); Liu Guoli, the pharmacological research of Flos Chrysanthemi Indici and clinical practice overview, the time precious traditional Chinese medicines research, 1991,2 (3)) at present, Flos Chrysanthemi Indici is that the preparation of raw material has oral formulations, Flos Chrysanthemi indici injection has the detoxifcation of inducing sweat.Be used for fever caused by exogenous pathogenic factors, conjunctival congestion and swelling pain, device larynx pain; Upper respiratory tract infection, acute tonsillitis belong to the person of attacking on the pyretic toxicity.Shen Lizhen, Flos Chrysanthemi is in the clinical practice of ophthalmology, China's TCM Ophthalmology magazine, 2001,11 (2), reported Flos Chrysanthemi (Flos Chrysanthemi, Herba Tagetis Patulae, Herba Dendranthematis indici), treatment external eyes febrile illness, as acute and chronic conjunctivitis, wherein Herba Dendranthematis indici is multiple in the disease of hyperactivity of toxic heat such as various chemical injuries, thermal burn, but do not report concrete medicinal material extract method, its concrete drug effect is unpredictable.Though the Flos Chrysanthemi Indici injection also has report to be used for ophthalmic diseases, but because raw material extracting method difference, injection is different with the prescription of eye drop, the selection difference of additives, at the particularity of eye with environment, injection can not be directly used in eye drop, still not have the report that Flos Chrysanthemi Indici is the feedstock production ophthalmic preparation at present, also not have to form the report of relevant product.
Summary of the invention
Solution of the present invention has provided a kind of medical composite for eye for the treatment of acute and chronic conjunctivitis, and another technical scheme of the present invention has provided this preparation of drug combination method.
The invention provides a kind of medical composite for eye for the treatment of acute and chronic conjunctivitis, it is that extract by Chinese medicine Flos Chrysanthemi Indici Chrysanthemum indicum L. is an active component, add the ophthalmic preparation that acceptable accessories or complementary composition are prepared from, wherein, contain total flavones in every preparation unit in rutin C27H30O16, must not be less than 0.5mg; Every 1ml contains chlorogenic acid C16H18O9 should be less than 30 μ g.Described every preparation unit is meant every ml of liquid preparation; Every g of solid preparation.
Wherein, described Flos Chrysanthemi Indici extract is to be extracted by following method: Flos Chrysanthemi Indici is added water, and second distillation is collected re-distilled liquid; Medicinal residues decoct with water, and 50%～80% ethanol is refining, reclaim ethanol, mix with re-distilled liquid, are Flos Chrysanthemi Indici extract.
Described preparation is: liquid preparation, semi-solid preparation.
Further, described semi-solid preparation is Eye ointments, ocular inserts, gel for eye.
Further, described liquid preparation is: eye drop, slow release eye drop.
Wherein, every 1ml contains total flavones with rutin (C in the described liquid preparation
27H
30O
16) meter, must not be less than 0.5mg; Every 1ml contains chlorogenic acid (C
16H
18O
9) should be less than 30 μ g.
Wherein, the pH value of described liquid preparation is 7.0～7.4.
Wherein, the every 1000ml of described eye drop is prepared from by following proportion raw material:
Flos Chrysanthemi Indici 1200～800g, Tween 80 8～3ml, glycerol 10～6ml, boric acid 10～6g, surplus is a water.
Further, the every 1000ml of described eye drop is prepared from by following proportion raw material:
Flos Chrysanthemi Indici 1000g, Tween 80 5ml, glycerol 8ml, boric acid 8g, surplus is a water.
The present invention also provides the preparation method of this medical composite for eye, and it comprises the steps:
Dry capitulum or the herb of a, the material Flos Chrysanthemi Indici Chrysanthemum indicum L. that gets it filled soak, use steam distillation through distillation, redistillation, collect re-distilled liquid, the residue medicinal residues;
B, the medicinal residues of a step are decocted with water, filter, concentrate, add ethanol and make that to contain the alcohol amount be 50%～80%, leave standstill, filter, reclaim ethanol, filter filtrate for later use;
C, the re-distilled liquid of a step is mixed with the filtrate of b step, add the adjuvant of pharmaceutically acceptable ophthalmic preparation or the ophthalmic preparation pharmaceutically commonly used that complementary composition is prepared from.
Medical composite for eye of the present invention, medicament sources is extensive, determined curative effect, stable and controllable for quality, side effect is little, effectively extract composition and be difficult for producing drug resistance, and prove by pharmacodynamics test, adopt ophthalmic preparation that raw material extracting method of the present invention is prepared from than former injection under identical raw material consumption, drug effect obviously is better than former injection, and satisfy the prescription of ophthalmic preparation, for the clinical medicine for the treatment of acute and chronic conjunctivitis that provides is newly selected.
Obviously, according to foregoing of the present invention,,, can also make modification, replacement or the change of other various ways not breaking away under the above-mentioned basic fundamental thought of the present invention prerequisite according to the ordinary skill knowledge and the customary means of this area.
The specific embodiment of form is described in further detail foregoing of the present invention again by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following example.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
The specific embodiment
The preparation of embodiment 1 medicine eye drop of the present invention
One, raw material: Flos Chrysanthemi Indici 1000g, Tween 80 5ml, glycerol 8ml, boric acid 8g, 20% sodium hydroxide are prepared 1000ml in right amount
Two, preparation technology
1, get Flos Chrysanthemi Indici 1000g, add 10 water gagings and soaked 1 hour, steam distillation is collected distillate 1000ml just, and redistillation is collected re-distilled liquid 500ml again, and is standby;
2, collect decoction liquor in the medicinal residues, filter, medicinal residues add 8 water gagings, decoct secondary, and each 1 hour, filter, merging filtrate, being concentrated into relative density is the clear paste of 1.14～1.18 (40～70 ℃), adds ethanol and makes and contain the alcohol amount and reach 65%, cold preservation was left standstill 12 hours;
3, filter, reclaim ethanol and also be concentrated into the clear paste that relative density is 1.16～1.22 (40～70 ℃), put coldly, add ethanol and make and contain the alcohol amount and reach 85%, stir evenly, cold preservation was placed 20 hours.Filter, filtrate recycling ethanol also is concentrated into does not have the alcohol flavor, adds the injection water to 500ml, and cold preservation 12 hours filters, and filtrate is heated to 80～90 ℃, adds 0.3% active carbon, stirs, keep 80～90 ℃ 30 minutes;
4, filter, filtrate adds the tween post-heating to boiling with 0.22 μ m fine straining, is chilled to room temperature, add re-distilled liquid 500ml, mixing adds all the other additives, regulates PH to 7.0～7.4 with 20% sodium hydroxide, add the injection water to 1000ml, 0.22 μ m filters, sterile filling, promptly.
Among the above-mentioned preparation technology, the selection of adjuvant and the scope of pH value are the key factors of preparation method of the present invention.
The preparation of experimental example 2 medicine eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption changes: Flos Chrysanthemi Indici 1200g, Tween 80 8ml, glycerol 10ml, an amount of, the boric acid 10g of 20% sodium hydroxide;
The preparation of experimental example 3 medicine eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption changes: Flos Chrysanthemi Indici 800g, Tween 80 3ml, an amount of, the boric acid 6g of 20% sodium hydroxide;
The preparation of experimental example 4 medicine eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption changes: Flos Chrysanthemi Indici 1000g, Tween 80 6ml, an amount of, the boric acid 6g of 20% sodium hydroxide;
The preparation of experimental example 5 medicine eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption changes: Flos Chrysanthemi Indici 1000～800g, Tween 80 5ml, glycerol 7ml, an amount of, the boric acid 8g of 20% sodium hydroxide;
The preparation of experimental example 6 medicine eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption and adjuvant change: Flos Chrysanthemi Indici 1000g, polysorbas20 7ml, sodium lauryl sulphate 6ml, an amount of, the boric acid 7g of phosphoric acid;
The preparation of experimental example 7 medicine eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption and adjuvant change: Flos Chrysanthemi Indici 1200～800g, sodium lauryl sulphate 4ml, glycerol 9ml, 20% sodium hydroxide an amount of, sodium chloride 7g, domiphen bromide 0.8ml;
The preparation of experimental example 8 medicament slow release eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption and adjuvant change: Flos Chrysanthemi Indici 1000g, carbomer 2.2g, hydroxypropyl methylcellulose 15.0g, sodium hydrogen phosphate 2.5g, sodium dihydrogen phosphate 5.0g, sodium chloride 5.0g, ethyl hydroxybenzoate 0.3g, 1M sodium hydroxide are an amount of;
The preparation of experimental example 9 medicament slow release eye drops of the present invention
Preparation technology is with embodiment 1, and just consumption and adjuvant change: Flos Chrysanthemi Indici 1000g; Carbomer 5g, hydroxypropyl methylcellulose 10g, sodium hydrogen phosphate 2.5g, sodium dihydrogen phosphate 2.5g, sodium chloride 3.0g, ethyl hydroxybenzoate 0.3g, 1M sodium hydroxide are an amount of;
The preparation of experimental example 10 medicine gel for eye use of the present invention
Preparation technology is with embodiment 1, and just consumption and adjuvant change: Flos Chrysanthemi Indici 1000g; Hyaluronic acid sodium 5.2g, hydroxypropyl methylcellulose 10g, boric acid 2.5g, sodium chloride 3.0g, ethyl hydroxybenzoate 0.3g, 1M sodium hydroxide are an amount of; Phenethanol 1.5ml
The preparation of experimental example 11 medicine gel for eye use of the present invention
Preparation technology is with embodiment 1, and just consumption and adjuvant change: Flos Chrysanthemi Indici 1000g; Hyaluronic acid sodium 5.2g, hydroxypropyl methylcellulose 10g, carbomer 3.5g; Boric acid 2.5g, sodium chloride 3.0g, ethyl hydroxybenzoate 0.6g
The experimental basis that additives are selected in the experimental example 12 medicine ophthalmic preparations of the present invention
The screening foundation of additives:
1, the selection of hydrotropy adjuvant
This product contains volatile oil, and dissolubility is little in water.For preventing that volatile oil from separating out, carried out prerun with reference to the former technology of Flos Chrysanthemi Indici injection, select for use 0.5% polyoxyethylene sorbitan monoleate to increase the dissolubility of volatile oil, increase stability of formulation.Result of the test shows that its solubilizing effect is better.
2, pH adjusts the selection of agent
PH value has significant effects to eye drop.The pH value of human body normal tear fluid is 7.4, comfort invariably when pH value is 6～8.Determine the pH value of eye drop, aspects such as main dissolubility from medicine, stability, zest are considered.The pH value of Flos Chrysanthemi Indici re-distilled liquid often is about 4.0, must add an amount of alkaline pH regulator agent.Alkaline pH regulator commonly used has sodium hydroxide (potassium) solution, liquor sodii citratis, phosphate buffer etc.Consider to contain flavones ingredient in this product that regulating pH with sodium hydroxide solution can increase its dissolubility, and with reference to the former technology of Flos Chrysanthemi Indici injection, selects the pH regulator agent of 20% sodium hydroxide solution as this product for use, and the pH regulator scope is selected.
Result of variations saw Table 1 before and after pH value was regulated.
Result of variations table before and after table 1 medicine eye drop of the present invention pH value is regulated
As seen from the above table, behind the pH regulator, pH value all descends to some extent in the storage, but different pH value is bigger to the stability influence of medicine eye drop of the present invention, and index components and effective ingredient all descend to some extent in the storage, because of adjust pH to 7.0～7.5 o'clock descend less, 6.0 medicinal liquid clarity was relatively poor in～6.5 o'clock, general flavone content descends also more, and aspects such as combination stability and zest are considered, select adjust pH to 7.0～7.5 more suitable.
3, the selection eye drop of antibacterial is the multiple dose preparation, needs to add antibacterial in principle.Consider that the contained effective ingredient of this product itself has good fungistatic effect, simultaneously antibacterial commonly used is carried out Preliminary screening, polyoxyethylene sorbitan monoleate has incompatibility in parabens antibacterial and this product, benzalkonium bromide and this product have incompatibility, the unstable easily oxidation of sorbic acid, thimerosal etc. consider that then its toxicity is bigger.And boric acid aqueous solution promptly has buffering, increases the principal agent dissolubility, regulates effects such as osmotic pressure.The effect of the antibacterial of inhibition and mycete is arranged again, increase the curative effect of this product.So selecting 1% boric acid for use is the antibacterial of this product, and its fungistatic effect is investigated.
Test method: get the 200g medical material, by above technological operation, medicinal liquid is added water for injection to 200ml, 0.22 μ m microporous filter membrane filters; Get 100ml, add 10g boric acid, make dissolving, 0.22 μ m microporous filter membrane filters, and in the infusion bottle of packing into, does not add a cover, solution was exposed in the air after two hours, seal bottle cap, jolting is after 0.5 hour, according to " 2000 editions one appendix XIIIC microbial limit test of Chinese pharmacopoeia is checked bacterial population, mycete, yeast, staphylococcus aureus, Pseudomonas aeruginosa.Experimental result sees Table 2.
Table 2 antibacterial is investigated
| The antibacterial kind | Antibacterial concentration | Sterilization effect | |||
| Bacterial population (individual/ml) | Mycete, yeast (individual/ml) | Staphylococcus aureus (individual/ml) | Pseudomonas aeruginosa (individual/ml) | ||
| Do not add antibacterial | 0 | 20 | Do not detect | Do not detect | Do not detect |
| Boric acid | 1％ | ＜10 | Do not detect | Do not detect | Do not detect |
Conclusion: the fungistatic effect that this eye drop adds behind the boric acid can reach requirement.And sample is through room temperature investigations that keep sample, and microbial limit meets eye drop and stipulates.
4, viscosity is adjusted the selection of agent
Suitably increase the viscosity of eye drop, can make medicine time of staying prolongation within the eye, help strengthening the curative effect of medicine, viscosity also can reduce zest after increasing simultaneously.According to viscosimetry (" two appendix VIG of Chinese pharmacopoeia version in 2000) second method eye drop viscosity is measured, the result is 4.0cPas.Take all factors into consideration, this product eye drop has comparatively suitable viscosity, can not add tackifier.
5, osmotic pressure is adjusted the selection of agent
The osmotic pressure of eye drop should ooze with tear (osmotic pressure value of normal tear fluid is 290m0smL) of people etc.The osmotic pressure scope that human eye can tolerate usually is equivalent to 0.8%～1.2% sodium chloride solution, is below or above this concentration and all can produces sense of discomfort.
Test method: make medicinal liquid by preparation technology, measure osmotic pressure.Result of the test sees Table 3.
Table 3 osmotic pressure is investigated
| Tested number | Osmotic pressure (mOsm/kg H 2O) |
| 1 2 3 | 337 345 329 |
Conclusion: the osmotic pressure of 0.8%～1.2% sodium chloride solution is 235～393mOsM after measured, and the osmotic pressure of visible this product need not add osmotic pressure regulator in the tolerance range of the normal limit of people.
The selection of above-mentioned additives as can be known, though pharmaceutical addition agent of the present invention is the conventional ophthalmic preparation adjuvant of using, but be not simple combination, but through creationary screening, analysis, comparison, additives and the consumption thereof selected all are unpredictable, the quality of the medicine of the present invention that the selection of additives effectively guarantees.
The method of quality control of embodiment 12 medicines of the present invention
Total flavones is measured according to ultraviolet spectrophotometry (2000 editions appendix V of Chinese Pharmacopoeia).
The preparation precision of reference substance solution takes by weighing at the control substance of Rutin 200mg of 120 ℃ of drying under reduced pressure to constant weight, puts in the 100ml measuring bottle, adds 70% ethanol 70ml, puts that slight fever makes dissolving in the water-bath, puts coldly, adds 70% ethanol to scale, shakes up.Precision is measured 10ml, puts in the 100ml measuring bottle, adds water to scale, shakes up, and promptly gets (containing anhydrous rutin 0.2mg among every 1ml).
The preparation precision of standard curve is measured reference substance solution 1.0ml, 2.0ml, 3.0ml, 4.0ml, 5.0ml, 6.0ml, puts respectively in the 25ml measuring bottle, adds water to 6ml, add 5% sodium nitrite solution 1ml, mixing was placed 6 minutes, added 10% aluminum nitrate solution 1ml, shake up, placed 6 minutes, hydro-oxidation sodium test solution 10ml adds water to scale again, shake up, placed 15 minutes; With corresponding solution is blank.According to spectrophotography (appendix VB), measure trap at 500nm wavelength place, be that vertical coordinate, concentration are abscissa with the trap, the drawing standard curve.
Algoscopy is got this product solution 1ml, puts in the 25ml measuring bottle, and the method under the preparation of sighting target directrix curve from " adding water to 6ml ", is measured trap in accordance with the law, reads the weight of rutin the need testing solution from standard curve, calculates, promptly.
The every 1ml of this product contains total flavones with rutin (C
27H
30O
16) meter, must not be less than 0.5mg.
Chlorogenic acid photograph high performance liquid chromatography (" appendix VID of 2 years versions of Chinese pharmacopoeia) measure.
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-0.4% phosphoric acid solution (13: 87) is a mobile phase; The detection wavelength is 327nm.Theoretical cam curve is calculated by the chlorogenic acid peak should be not less than 2500.
It is an amount of that the preparation precision of reference substance solution takes by weighing the chlorogenic acid reference substance, puts in the brown volumetric flask, adds 50% methanol and make the solution that every 1ml contains 30 μ g, promptly gets (preserving below 10 ℃).
The preparation of need testing solution is got this product as test sample.
Accurate respectively reference substance solution and each the 10 μ l injection chromatograph of liquid of need testing solution drawn of algoscopy measured, promptly.
The every 1ml of this product contains chlorogenic acid (C
16H
18O
9) should be less than 30 μ g.
Mainly contain total flavones and chlorogenic acid in the Flos Chrysanthemi Indici, the chlorogenic acid instability, it only is the purpose that quality control index can not effectively reach quality control with the chlorogenic acid, therefore, selecting total flavones simultaneously is the index components of quality control, total flavones is the main active in the Flos Chrysanthemi Indici, has both reached the purpose of quality control, the drug effect that how much has directly reflected medicine again of its amount.
Below prove beneficial effect of the present invention by pharmacodynamics test.
Test example 1 medicine of the present invention is to the therapeutical effect of rabbit experiment infection of staphylococcus aureus membranous conjunctivitis
Test material:
1, trial drug
(1) is subjected to the reagent thing
Medicine eye drop of the present invention, 5mL/ props up, and drug level is respectively 2g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 2g), lot number: 040704; 1g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 1g), lot number: 040703; 0.5g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 0.5g), lot number: 040705.Above each concentration liquid of medicine eye drop of the present invention is by the method preparation of embodiment 1, and 1g crude drug/mL medicine eye drop of the present invention is a clinical dosage.
Flos Chrysanthemi indici injection 1g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 1g) is provided lot number 040301 by Sanjiu Pharmaceutical Industry Co., Ltd., Ya'an City.
(2) positive control medicine: Chloramphenicol Eye Drop.8mL (20mg)/.Produce lot number: 040212 by Sichuan Taihuatang Pharmaceutical Co.,Ltd.
2, bacterial strain
Staphylococcus aureus ATCC25923, concentration is 1 * 10
8Individual bacterium/mL.Carry out antibacterial culturing, prepare and provide by microbiology teaching and research room of Chengdu University of Traditional Chinese Medicine.
3, animal
Rabbit, blood-shot eye illness, white hair, one-level, body weight 1.95～2.25kg, male and female dual-purpose.Provide the animal quality certification number by plant of Sichuan Province's laboratory animal special commission: the real moving pipe matter 2004-14 in river.
4, test method
(1) conjunctivitis replication of Model method: according to the method that document is introduced, (concentration is 1 * 10 to the suspension that a following face and the bulbar conjunctiva intersection of rabbit eyes are injected staphylococcus aureus
8The 0.1mL/ eye of individual bacterium/mL) causes infection of staphylococcus aureus membranous conjunctivitis model;
(2) grouping and drug dose: the injection staphylococcus aureus cause the conjunctivitis model after 24 hours (the 2nd day) according to severe extent with 40 of rabbit by sex evenly collocation be divided into 8 groups, 5 every group (male and female dual-purpose) totally 10 eyes is used for experiment.Conduct respectively: 1. normal control group: normal saline equal-volume eye drip; 2. model control group: normal saline equal-volume eye drip; 3. Chloramphenicol Eye Drop (positive control medicine) is organized: 0.24mg/kg (concentration is 2.5mg/mL, and two drip medicines, 24 μ L/ eyes/time, 4 times/day); 4.～6. the high, medium and low three kinds of dosage groups of medicine eye drop of the present invention: 0.192,0.096,0.048g crude drug/kg (two drip medicines, 24 μ L/ eyes/time, 4 times/day.); 7.～8. former dosage form Flos Chrysanthemi indici injection high and low dose group: 0.096,0.048g crude drug/kg (two drip medicines, 24 μ L/ eyes/time, high dose 4 times/day, low dosage 2 times/day.)。
(3) medicine-feeding way and method: the injection staphylococcus aureus cause the conjunctivitis model after 24 hours (the 2nd day) evenly divide into groups according to severe extent, begin then with normal saline, medicine eye drop of the present invention, former dosage form Flos Chrysanthemi indici injection and Chloramphenicol Eye Drop eye drip, continuous 7 days.
(4). observation index: before every morning the 1st eye drip medicinal liquid, give eye drop more respectively after stimulating the comprehensive grading standard to observe and write down the conjunctivitis degree by eye earlier.
Conjunctivitis grading standards of grading:
1. congested: blood vessel is normal: 0 minute; The congestion of blood vessel is cerise: 1 minute; The congestion of blood vessel is peony, and blood vessel is difficult for differentiating: 2 minutes; Diffusivity hyperemia is aubergine: 3 minutes.
2. edema: no edema: 0 minute; Slight edema: 1 minute; Obvious edema is with the part ectropion of lid: 2 minutes; Edema is to the nearly semi-closed of eyelid: 3 minutes; Edema to eyelid surpasses semi-closed: 4 minutes.
3. secretions: no secretions: 0 minute; A small amount of secretions: 1 minute; Secretions makes eyelid and eyelashes are moist or adhesion: 2 minutes; Secretions makes whole eye district and eyelashes are moist or adhesion: 3 minutes.
(5) meter method: data are represented with x ± S, relatively checking with Dunnett t between two groups.
(6) result of the test
The results are shown in Table 4,
As seen, (concentration is 1 * 10 to the suspension that a following face and the bulbar conjunctiva intersection of two eyes of rabbit are injected staphylococcus aureus from table 4 and test
8The 0.1mL/ eye of individual bacterium/mL) causes infection of staphylococcus aureus membranous conjunctivitis model.After causing scorching 24 hours, visible bulbar conjunctiva and the hyperemia of palpebral conjunctiva diffusivity are aubergine, edema serious unusually (relatively pathological changes is still obvious with the normal control group after 7 days for model control group), and one's eyes became bloodshot, inflammation secretions many (especially infecting the back 1～3 day).Medicine eye drop of the present invention and positive control medicine Chloramphenicol Eye Drop have significant therapeutical effect.(the 0.192g crude drug/kg) treatment can make symptoms such as conjunctivitis hyperemia, edema, secretions significantly alleviate (P＜0.05) after 3 days to medicine eye drop high dose group of the present invention; (clinical dosage), low dose group in the medicine eye drop of the present invention (0.096,0.048g crude drug/kg) and former dosage form Flos Chrysanthemi indici injection (0.096, the 0.048g crude drug/kg) treatment can make symptoms such as conjunctivitis hyperemia, edema, secretions significantly alleviate (P＜0.05) after 5 days.Illustrate that medicine eye drop of the present invention and former dosage form injection all have therapeutical effect to rabbit conjunctivitis due to the infection of staphylococcus aureus, treat and can cure after 7 days (with the normal control group relatively, P＞0.05).
Experimental example 2 medicine eye drops of the present invention are to the effect of rabbit viral conjunctivitis
1, test material
(1) is subjected to the reagent thing
Medicine eye drop of the present invention, 5mL/ props up, and drug level is respectively 2g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 2g), lot number: 040704; 1g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 1g), lot number: 040703; 0.5g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 0.5g), lot number: 040705.Above each concentration liquid of medicine eye drop of the present invention is by the method preparation of embodiment 1, and 1g crude drug/mL medicine eye drop of the present invention is a clinical dosage.
Flos Chrysanthemi indici injection 1g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 1g), lot number 040301 is provided by Sanjiu Pharmaceutical Industry Co., Ltd., Ya'an City.
(2) positive control medicine: aciclovir eye drop, 8ml: 8mg, this product is colourless clear liquid.Lot number 20030509 is produced by Qianjiang, Hubei pharmaceutical factory.
(3). Strain
Herpes simplex virus I-type (HSV-I), TCID
50Be 10
-9, provided by the calibrating of Beijing pharmaceutical biological product.
(4) animal
Rabbit, blood-shot eye illness, white hair, one-level, body weight 2.25～2.50kg, male and female dual-purpose.Provide the animal quality certification number by plant of Sichuan Province's laboratory animal special commission: the real moving pipe matter 2004-14 in river.
2, test method
(1) conjunctivitis replication of Model method: according to the method for document introduction, to a following face of two eyes of rabbit and the suspension (TCID of bulbar conjunctiva intersection injection herpes simplex virus I-type
50Be 10
-9) the 0.1mL/ eye, cause infectious herpes simplex virus I-type conjunctivitis model.
(2) grouping and drug dose: the injection herpes simplex virus I-type cause the conjunctivitis model after 24 hours (the 2nd day) according to severe extent with 40 of rabbit by sex evenly collocation be divided into 8 groups, 5 every group (male and female dual-purpose) totally 10 eyes is used for experiment.Conduct respectively: 1. normal control group: normal saline equal-volume eye drip; 2. model control group: normal saline equal-volume eye drip; 3. aciclovir eye drop (positive control medicine) is organized: 0.096mg/kg (concentration is 1mg/mL, and two drip medicines, 24 μ L/ eyes/time, 4 times/day); 4.～6. the high, medium and low three kinds of dosage groups of medicine eye drop of the present invention: 0.192,0.096,0.048g crude drug/kg (two drip medicines, 24 μ L/ eyes/time, 4 times/day.); 7.～8. former dosage form Flos Chrysanthemi indici injection high and low dose group: 0.096,0.048g crude drug/kg (two drip medicines, 24 μ L/ eyes/time, high dose 4 times/day, low dosage 2 times/day.)。
(3) medicine-feeding way and method: the injection herpes simplex virus I-type cause the conjunctivitis model after 24 hours (the 2nd day) according to the severe extent grouping of evenly arranging in pairs or groups, begin then with normal saline, medicine eye drop of the present invention, former dosage form Flos Chrysanthemi indici injection and aciclovir eye drop eye drip, continuous 7 days.
(4). observation index: before every morning the 1st dripping eyedrop, press earlier that the comprehensive grading method is observed and record conjunctiva inflammation degree score value after distinguish the eye drip medicinal liquid again.
Conjunctivitis grading standards of grading:
1. congested: blood vessel is normal: 0 minute; The congestion of blood vessel is cerise: 1 minute; The congestion of blood vessel is peony, and blood vessel is difficult for differentiating: 2 minutes; Diffusivity hyperemia is aubergine: 3 minutes.
2. edema: no edema: 0 minute; Slight edema: 1 minute; Obvious edema is with the part ectropion of lid: 2 minutes; Edema is to the nearly semi-closed of eyelid: 3 minutes; Edema to eyelid surpasses semi-closed: 4 minutes.
3. secretions: no secretions: 0 minute; A small amount of secretions: 1 minute; Secretions makes eyelid and eyelashes are moist or adhesion: 2 minutes; Secretions makes whole eye district and eyelashes are moist or adhesion: 3 minutes.
(5) statistical method: data are represented with x ± S, relatively checking with Dunnett t between two groups.
(6) result of the test
The results are shown in Table 5,
From table 5 and test, as seen, the following face of two eyes of rabbit and bulbar conjunctiva intersection are injected the suspension (TCID of herpes simplex virus I-type
50Be 10
-9) the 0.1mL/ eye, cause herpes simplex virus I-type infective conjunctivitis model.After causing scorching 24 hours, visible conjunctival congestion, rheuminess thing many (especially treating 3～5 days).Medicine eye drop of the present invention and positive control medicine aciclovir eye drop have significant therapeutical effect.Medicine eye drop height of the present invention, middle dosage (clinical dosage) group (0.192, the 0.096g crude drug/kg) treatment can make symptoms such as conjunctivitis hyperemia, edema, secretions significantly alleviate (p＜0.05) after 5 days; And former dosage form Flos Chrysanthemi indici injection does not have therapeutical effect (p＞0.05) to the infectious rabbit conjunctivitis model of herpes simplex virus I-type.Explanation is on rabbit conjunctivitis due to the infection of treatment herpes simplex virus I-type, and medicine eye drop of the present invention is better than former dosage form Flos Chrysanthemi indici injection.
Experimental example 3 medicine eye drops of the present invention are to the effect of rabbit NBC
1, test material
(1) is subjected to the reagent thing
Medicine eye drop of the present invention, 5mL/ props up, and drug level is respectively 2g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 2g), lot number: 040704; 1g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 1g), lot number: 040703; 0.5g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 0.5g), lot number: 040705.Above each concentration liquid of medicine eye drop of the present invention is by the method preparation of embodiment 1, and 1g crude drug/mL medicine eye drop of the present invention is a clinical dosage.
Flos Chrysanthemi indici injection 1g crude drug/mL (every mL is equivalent to contain Flos Chrysanthemi Indici primary crude drug 1g) is provided lot number 040301 by Sanjiu Pharmaceutical Industry Co., Ltd., Ya'an City.
(2) positive control medicine: Chloramphenicol Eye Drop.8mL (20mg)/.Produce lot number: 040212 by Sichuan Taihuatang Pharmaceutical Co.,Ltd.
(3) proinflammatory agent
Oleum Tiglii, concocting teaching and research room by Chengdu University of Traditional Chinese Medicine provides, and Oleum Tiglii and vegetable oil were by dilution in 1: 20, and is standby.
(4) animal
Rabbit, one-level, body weight 1.90～2.20kg, male and female dual-purpose.Provide the animal quality certification number by plant of Sichuan Province's laboratory animal special commission: the real moving pipe matter 2004-14 in river.
2, test method
(1). conjunctivitis replication of Model method: the method according to document is introduced, splash into Oleum Tiglii 0.05ml (Oleum Tiglii dilutes by 1: 20 with vegetable oil) respectively in every rabbit right and left eyes conjunctival sac during experiment, closed eyelid massaged for 10 seconds gently, caused inflammation.Cause Oleum Tiglii membranous conjunctivitis model.
(2) grouping and drug dose: after Oleum Tiglii causes the conjunctivitis model 30 minutes, according to severe extent with 40 of rabbit by sex, inflammation degree evenly collocation be divided into 8 groups, 5 every group (male and female dual-purpose) totally 10 eyes is used for experiment.Conduct respectively: 1. normal control group: normal saline equal-volume eye drip; 2. model control group: normal saline equal-volume eye drip; 3. Chloramphenicol Eye Drop (positive control medicine) is organized: 0.24mg/kg (concentration is 2.5mg/mL, and two drip medicines, 24 μ L/ eyes/time, 4 times/day); 4.～6. the high, medium and low three kinds of dosage groups of medicine eye drop of the present invention: 0.192,0.096,0.048g crude drug/kg (two drip medicines, 24 μ L/ eyes/time, 4 times/day.); 7.～8. former dosage form Flos Chrysanthemi indici injection high and low dose group: 0.096,0.048g crude drug/kg (two drip medicines, 24 μ L/ eyes/time, high dose 4 times/day, low dosage 2 times/day.)。
(3). medicine-feeding way and method: after Oleum Tiglii causes the conjunctivitis model 30 minutes, according to severe extent rabbit is evenly divided into groups, use normal saline, medicine eye drop of the present invention, Chloramphenicol Eye Drop and former dosage form Flos Chrysanthemi indici injection eye drip respectively.
(4) observation index: after the administration first time, checked in 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours and record conjunctiva inflammation degree and scoring.
Conjunctivitis grading standards of grading:
1. congested: blood vessel is normal: 0 minute; The congestion of blood vessel is cerise: 1 minute; The congestion of blood vessel is peony, and blood vessel is difficult for differentiating: 2 minutes; Diffusivity hyperemia is aubergine: 3 minutes.
2. edema: no edema: 0 minute; Slight edema: 1 minute; Obvious edema is with the part ectropion of lid: 2 minutes; Edema is to the nearly semi-closed of eyelid: 3 minutes; Edema to eyelid surpasses semi-closed: 4 minutes.
3. secretions: no secretions: 0 minute; A small amount of secretions: 1 minute; Secretions makes eyelid and eyelashes are moist or adhesion: 2 minutes; Secretions makes whole eye district and eyelashes are moist or adhesion: 3 minutes.
(5) statistical method: data are represented with x ± S, relatively checking with Dunnett t between two groups.
(6) result of the test
Appraisal result sees Table 6
Table 6 result shows, cause the conjunctivitis model after 30 minutes at Oleum Tiglii, as seen one's eyes became bloodshot, edema is serious, secretions is many, ((treatment of 0.096g crude drug/kg, 0.048g crude drug/kg) is after 1 hour for 0.192g crude drug/kg, 0.096g crude drug/kg, 0.048g crude drug/kg) and former dosage form Flos Chrysanthemi indici injection with medicine eye drop of the present invention, compare with model group, promptly visible hyperemia, edema symptom obviously alleviate, and secretions reduces.Illustrate that medicine eye drop of the present invention and former dosage form Flos Chrysanthemi indici injection all have obvious suppression effect (P＜0.05) to the rabbit NBC due to the Oleum Tiglii.Medicine eye drop clinical dosage treatment back 48h of the present invention, the basic healing, compare with the normal control group, P＞0.05, and former dosage form Flos Chrysanthemi indici injection group is compared with the normal control group, and is still variant, P＜0.05, the caused rabbit conjunctivitis of treatment Oleum Tiglii is described, medicine eye drop of the present invention is more excellent than former dosage form Flos Chrysanthemi indici injection.
Above-mentioned pharmacodynamics test explanation: medicine eye drop of the present invention has following effect for the acute and chronic conjunctivitis of treatment:
(1) to the therapeutical effect of rabbit experiment infection of staphylococcus aureus membranous conjunctivitis
In the therapeutical effect test to rabbit experiment infection of staphylococcus aureus membranous conjunctivitis, (the 0.192g crude drug/kg) treatment can make symptoms such as conjunctivitis hyperemia, edema, secretions significantly alleviate (P＜0.05) after 3 days to medicine eye drop high dose group of the present invention; (clinical dosage), low dose group in the medicine eye drop of the present invention (0.096,0.048g crude drug/kg) and former dosage form Flos Chrysanthemi indici injection (0.096, the 0.048g crude drug/kg) treatment can make symptoms such as conjunctivitis hyperemia, edema, secretions significantly alleviate (P＜0.05) after 5 days.And treat after 7 days and can cure (comparing P＞0.05) with the normal control group.Illustrate that medicine eye drop of the present invention and former dosage form injection all have therapeutical effect to rabbit conjunctivitis due to the infection of staphylococcus aureus.
(2) medicine eye drop of the present invention is to the effect of rabbit viral conjunctivitis
Medicine eye drop of the present invention to the effect of rabbit viral conjunctivitis test in, medicine eye drop height of the present invention, middle dosage (clinical dosage) group (0.192, the 0.096g crude drug/kg) treatment can make symptoms such as conjunctivitis hyperemia, edema, secretions significantly alleviate (p＜0.05) after 5 days; And former dosage form Flos Chrysanthemi indici injection does not have therapeutical effect (p＞0.05) to the infectious rabbit conjunctivitis model of herpes simplex virus I-type.Explanation is on rabbit conjunctivitis due to the infection of treatment herpes simplex virus I-type, and medicine eye drop of the present invention is better than Flos Chrysanthemi indici injection.
(3) medicine eye drop of the present invention is to the effect of rabbit NBC
In effect test to the rabbit NBC, ((treatment of 0.096g crude drug/kg, 0.048g crude drug/kg) is after 1 hour for 0.192g crude drug/kg, 0.096g crude drug/kg, 0.048g crude drug/kg) and former dosage form Flos Chrysanthemi indici injection with medicine eye drop of the present invention, compare with model group, promptly visible hyperemia, edema symptom obviously alleviate, and secretions reduces.Illustrate that medicine eye drop of the present invention and former dosage form Flos Chrysanthemi indici injection all have obvious suppression effect (P＜0.05) to the rabbit NBC due to the Oleum Tiglii.In addition, treating back 24h with medicine eye drop 0.192g crude drug of the present invention/kg, conjunctivitis is cured substantially, compares P＞0.05 with the normal control group; Medicine eye drop 0.096g crude drug/kg of the present invention (clinical dosage) treatment back 48h, the basic healing, compare with the normal control group, P＞0.05, and former dosage form Flos Chrysanthemi indici injection group is compared with the normal control group, and is still variant, P＜0.05, the caused rabbit conjunctivitis of treatment Oleum Tiglii is described, medicine eye drop of the present invention is more excellent than former dosage form Flos Chrysanthemi indici injection.
Above-mentioned pharmacodynamics test explanation, under identical raw material consumption, the drug effect of medicine eye drop of the present invention obviously is better than Flos Chrysanthemi indici injection, and the generation of this effect is not to be only to produce owing to the change of dosage form, it is caused by raw material extracting method difference, for a person skilled in the art, be not to be apparently, can know by inference, therefore, ophthalmic preparation of the present invention provides a kind of new selection for clinical.
Table 4 medicine eye drop of the present invention is to the therapeutical effect (a comprehensive grading x ± S N=10 eye) of rabbit conjunctivitis due to the infection of staphylococcus aureus
| Administration time | The normal control group | Model control group | Inflammation degree comprehensive grading (branch) | |||||
| Chloramphenicol Eye Drop | Medicine eye drop high dose group of the present invention | Dosage group in the medicine eye drop of the present invention | Medicine eye drop low dose group of the present invention | Flos Chrysanthemi indici injection flower injection high dose group | The Herba Dendranthematis indici low dose group | |||
| Treatment treatment in 1 day treatment in 2 days treatment in 3 days treatment in 4 days treatment in 5 days treatment in 6 days is 7 days before the administration | 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * | 2.8±0.79 △ 2.6±0.70 △ 2.3±0.48 △ 2.4±0.70 △ 1.8±0.79 △ 1.8±0.92 △ 1.4±0.70 △ 1.2±0.63 △ | 3.0±0.67 △ 2.8±0.79 △ 1.2±1.14 *△ 0.7±0.67 *△ 0.6±0.70 *△ 0.2±0.42 * 0.2±0.42 * 0.1±0.32 * | 3.2±1.23 △ 3.0±1.56 △ 1.6±1.07 △ 1.6±0.70 *△ 1.1±0.32 *△ 0.9±0.32 *△ 0.5±0.71 *△ 0.2±0.42 * | 3.2±0.42 △ 3.0±0.47 △ 2.1±1.20 △ 2.3±1.25 △ 1.4±0.84 △ 1.0±0.67 *△ 0.7±0.48 *△ 0.4±0.52 * | 3.0±0.94 △ 2.8±1.23 △ 1.9±1.29 △ 2.1±0.88 △ 1.3±0.67 △ 0.8±0.63 *△ 0.5±0.71 *△ 0.3±0.48 * | 3.1±0.32 △ 3.0±0.47 △ 1.9±0.88 △ 2.2±0.79 △ 1.3±0.48 △ 0.9±0.57 *△ 0.7±0.48 *△ 0.4±0.52 * | 3.1±0.57 △ 3.0±0.67 △ 1.8±0.63 △ 2.0±0.47 △ 1.4±0.52 △ 0.7±0.67 *△ 0.5±0.53 *△ 0.3±0.48 * |
Annotate: compare with model control group,
*P＜0.05; Compare △ P＜0.05 with the normal control group
The therapeutical effect (a comprehensive grading x ± S N=10 eye) of rabbit conjunctivitis due to table 5 medicine eye drop of the present invention infects herpes simplex virus I-type
| Administration time | The normal control group | Model control group | Inflammation degree comprehensive grading (branch) | |||||
| Aciclovir eye drop | Medicine eye drop high dose group of the present invention | Dosage group in the medicine eye drop of the present invention | Medicine eye drop liquid low dose group of the present invention | The Flos Chrysanthemi indici injection high dose group | Flos Chrysanthemi Indici injection low dose group | |||
| Treatment treatment in 1 day treatment in 2 days treatment in 3 days treatment in 4 days treatment in 5 days treatment in 6 days is 7 days before the administration | 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * 0±0 * | 1.6±0.97 △ 1.5±1.08 △ 2.3±0.67 △ 2.6±1.07 △ 2.8±0.92 △ 2.0±0.67 1.9±0.74 △ 1.6±0.70 △ | 1.8±0.79 △ 1.3±1.16 △ 2.6±1.07 △ 1.3±1.16 *△ 1.0±0.82 *△ 1.1±0.74 *△ 0.7±0.48 *△ 0.3±0.48 * | 1.7±0.95 △ 1.5±1.43 △ 2.7±0.95 △ 1.8±1.13 △ 2.1±1.29 △ 1.4±0.52 *△ 1.0±0.82 *△ 0.7±0.67 *△ | 1.6±0.52 △ 1.9±0.74 △ 1.7±0.95 △ 2.0±0.67 △ 2.3±0.82 △ 1.6±1.35 *△ 1.1±0.74 *△ 0.8±0.42 *△ | 1.8±0.79 △ 1.6±0.84 △ 2.5±1.35 △ 2.0±1.33 △ 2.7±1.64 △ 2.5±1.84 △ 1.5±1.27 △ 1.6±1.17 △ | 1.7±0.48 △ 2.2±1.03 △ 2.0±0.67 △ 2.2±0.42 △ 2.1±0.74 △ 2.6±1.07 △ 1.3±0.82 △ 1.2±0.63 △ | 1.8±0.92 △ 1.8±1.40 △ 2.3±0.95 △ 2.7±1.06 △ 2.2±0.42 △ 2.3±0.95 △ 1.7±0.67 △ 1.6±0.70 △ |
Annotate: compare with model control group,
*P＜0.05; Compare △ P＜0.05 with the normal control group
Table 6 medicine eye drop of the present invention is to the influence (an x ± S N=10 eye) of rabbit acute conjunctivitis due to the Oleum Tiglii
| Group | Eyeball (only) | Dosage (g/kg) | Before the administration | 1h | 2h | 4h | 8h | 24h | 48h |
| Normal group model group chloromycetin group medicine eye drops of the present invention medicine eye drops of the present invention medicine eye drops of the present invention Flos Chrysanthemi indici injection group Flos Chrysanthemi indici injection group | 10 10 10 10 10 10 10 10 | Equal-volume equal-volume 0.24mg/kg 0.192 0.096 0.048 0.096 0.048 | 0±0* 6.4±1.07 6.4±1.65 5.9±1.45 6.0±1.49 5.9±1.66 6.1±1.66 5.9±1.52 | 0±0* 6.4±1.71 △ 3.5±0.53* △ 4.6±1.27* △ 3.4±0.84* △ 4.2±0.79* △ 4.0±1.33* △ 3.5±0.85* △ | 0±0* 5.5±1.58 △ 3.2±0.42* △ 2.0±1.33* △ 2.6±0.52* △ 3.3±0.48* △ 4.0±1.89* △ 3.0±1.15* △ | 0±0* 2.9±0.57 △ 1.0±0.82* △ 1.2±1.23* △ 2.0±0.94* △ 1.9±1.20* △ 1.6±0.52* △ 2.7±0.48 △ | 0±0* 2.2±0.79 △ 0.2±0.42* 0.7±0.82* △ 0.9±0.74* △ 1.0±0.67* △ 0.8±0.63* △ 2.2±0.79 △ | 0±0* 1.6±0.52 △ 0.1±0.32* 0.2±0.42* 0.5±0.71* △ 1.1±0.32* △ 0.9±0.74* △ 1.4±0.52 △ | 0±0* 1.4±0.84 △ 0.0±0.0* 0.1±0.32* 0.2±0.42* 0.8±0.63* △ 0.7±0.95* △ 1.3±0.48 △ |
Annotate: compare with model group, △ P＜0.05 is compared with the normal control group in * P＜0.05
Claims (10)
1, a kind of medical composite for eye for the treatment of acute and chronic conjunctivitis, it is characterized in that: it is that extract by Chinese medicine Flos Chrysanthemi Indici Chrysanthemum indicum L. is an active component, add the ophthalmic preparation that acceptable accessories or complementary composition are prepared from, wherein, contain total flavones in every preparation unit with rutin C
27H
30O
16Meter must not be less than 0.5mg; Every 1ml contains chlorogenic acid C
16H
18O
9Should be less than 30 μ g.
2, the medical composite for eye of the acute and chronic conjunctivitis of treatment according to claim 1 is characterized in that: described Flos Chrysanthemi Indici extract is to be extracted by following method: Flos Chrysanthemi Indici is added water, and second distillation is collected re-distilled liquid; Medicinal residues decoct with water, 50%～80% ethanol refining, reclaim ethanol, mix with re-distilled liquid, are Flos Chrysanthemi Indici extract.
3, the medical composite for eye of the acute and chronic conjunctivitis of treatment according to claim 1 and 2, it is characterized in that: described preparation is: liquid preparation, semi-solid preparation.
4, the medical composite for eye of the acute and chronic conjunctivitis of treatment according to claim 3, it is characterized in that: described semi-solid preparation is: Eye ointments, ocular inserts, gel for eye.
5, the medical composite for eye of the acute and chronic conjunctivitis of treatment according to claim 3, it is characterized in that: described liquid preparation is: eye drop, slow release eye drop.
6, the medical composite for eye of the acute and chronic conjunctivitis of treatment according to claim 5 is characterized in that: every 1ml contains total flavones with rutin C in the described liquid preparation
27H
30O
16Meter must not be less than 0.5mg; Every 1ml contains chlorogenic acid C
16H
18O
9Should be less than 30 μ g.
7, according to the medical composite for eye of claim 5 or the acute and chronic conjunctivitis of 6 described treatments, it is characterized in that: the pH value of described liquid preparation is 7.0～7.4.
8, the medical composite for eye of the acute and chronic conjunctivitis of treatment according to claim 7 is characterized in that: the every 1000ml of described eye drop is prepared from by following proportion raw material medical material and adjuvant:
Flos Chrysanthemi Indici 1200～800g, Tween 80 8～3ml, glycerol 10～6ml, boric acid 10～6g, surplus is a water.
9, the medical composite for eye of the acute and chronic conjunctivitis of treatment according to claim 8 is characterized in that: the every 1000ml of described eye drop is prepared from by following proportion raw material medical material and adjuvant:
Flos Chrysanthemi Indici 1000g, Tween 80 5ml, glycerol 8ml, boric acid 8g, surplus is a water.
10, a kind of method for preparing the medical composite for eye of the acute and chronic conjunctivitis of the described treatment of claim 1, it comprises the steps:
Dry capitulum or the herb of a, the material Flos Chrysanthemi Indici Chrysanthemum indicum L. that gets it filled soak, use steam distillation through distillation, redistillation, collect re-distilled liquid, the residue medicinal residues;
B, the medicinal residues of a step are decocted with water, filter, concentrate, add ethanol and make that to contain the alcohol amount be 50%～80%, leave standstill, filter, reclaim ethanol, filter filtrate for later use;
C, the re-distilled liquid of a step is mixed with the filtrate of b step, add the adjuvant of pharmaceutically acceptable ophthalmic preparation or the ophthalmic preparation pharmaceutically commonly used that complementary composition is prepared from.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104173250A (en) * | 2014-09-12 | 2014-12-03 | 皖南医学院 | Skin-nourishing liquid soap containing natural bacteriostatic components and preparation method thereof |
| WO2018133618A1 (en) * | 2017-01-23 | 2018-07-26 | 四川九章生物科技有限公司 | Use of chlorogenic acid in preparation of drug for preventing and treating ocular inflammation |
-
2005
- 2005-01-31 CN CN 200510020285 patent/CN1813843A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104173250A (en) * | 2014-09-12 | 2014-12-03 | 皖南医学院 | Skin-nourishing liquid soap containing natural bacteriostatic components and preparation method thereof |
| WO2018133618A1 (en) * | 2017-01-23 | 2018-07-26 | 四川九章生物科技有限公司 | Use of chlorogenic acid in preparation of drug for preventing and treating ocular inflammation |
| CN108338980A (en) * | 2017-01-23 | 2018-07-31 | 四川九章生物科技有限公司 | Purposes of the chlorogenic acid in the drug for preparing prevention inflammation of eye section |
| CN114886882A (en) * | 2017-01-23 | 2022-08-12 | 四川九章生物科技有限公司 | Application of chlorogenic acid in preparing medicine for preventing and treating eye inflammation |
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