CN101130083A - Ophthalmic composition, producing method and use of the same - Google Patents
Ophthalmic composition, producing method and use of the same Download PDFInfo
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- CN101130083A CN101130083A CNA2007100151976A CN200710015197A CN101130083A CN 101130083 A CN101130083 A CN 101130083A CN A2007100151976 A CNA2007100151976 A CN A2007100151976A CN 200710015197 A CN200710015197 A CN 200710015197A CN 101130083 A CN101130083 A CN 101130083A
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Abstract
The invention discloses an eye composition and making method and application with antibiotic antiphlogistic activity, which consists of (a) one or more antibiotics or carbostyrile antibacterial drugs and (b) glycyrrhizic acid activator. The making method comprises the following steps: transmitting the composition and at least one liquid or semi-liquid carrier or adjuvant into eye agent to treat opthalmitis and bacterial infection. The invention can reduce side effect greatly.
Description
Technical field
The invention belongs to the medical and health technology field, relate to a kind of ophthalmic composition, its manufacture method and purposes, relate in particular to a kind of Radix Glycyrrhizae acids activating agent and antibiotic or Comprecin and excipient composition ophthalmic composition of containing.
Background technology
Steroid hormone class medicine and antibiotic or Comprecin are united use, be used for the treatment of and prevent the existing a lot of launch of eye inflammation and eye bacterial infection, the mechanism of action is that antibiotic or Comprecin can be prevented and treated the camera oculi anterior bacterial infection, hormone medicine all has therapeutical effect to inflammation and the allergic disease that the eye a variety of causes causes, its compound preparation can be removed the pathogen that causes infection clinically, and reaction simultaneously reduces inflammation.Gentamycin sulfate/fluorometholone eye drop as listing, gentamycin/prednisolone acetate ophthalmic suspension and gel for eye use, prednisolone acetate/polygynax/polymyxin ophthalmic suspension, tobramycin/dexamethasone eye drop, polygynax/dexamethasone sodium phosphate eye drop etc.
Cause glaucoma owing to eye prolonged application steroid may make intraocular pressure raise, also may cause the back subcapsular cataract and form.Eye prolonged application steroid also may cause the cornea attenuation, may cause perforation of eyeball at cornea or sclera patient's application class sterin of attenuation.This medicine of prolonged application may cause non-sensitive bacterium undue growth.The possibility of cornea fungal infection may appear in long-term prescription, the delay that also can cicatrize a wound of topical application corticosteroid.Long its application also may cause optic nerve lesion, defect of visual field and visual deterioration, and therefore, the application of this class medicine is restricted.
Glycyrrhizic acid is one of most important active ingredient in the Radix Glycyrrhizae, as Radix Glycyrrhizae extractum, glycyrrhizic acid, enoxolone, monopotassium glycyrrhizunate, monoammonium glycyrrhizinate, 18beta-Glycyrrhizic acid monosodium salt, glycyrrhizic acid dipotassium salt, diammonium glycyrhetate, disodium glycyrrhizinate, trisodium glycyrrhetinate salt etc.Radix Glycyrrhizae acids activating agent has effects such as antiinflammatory, antiviral, protecting liver and detoxication and antiallergic.Hao Fei is at glycyrrhizic acid foreign study progress (China Dispensary, 2001,12 (8): mention 500～501), because glycyrrhizic acid is structurally similar to glucocorticoid, can delay the metabolism of glucocorticoid in vivo, and hypothalamus-epinephrine axle is not had obvious influence, thus can be used as the alternative medicine of glucocorticoid, be used for the treatment of at present dermatitis, drug eruption, connective tissue disease and with closely-related disease of autoimmune such as psoriasis etc.
Finney RSH, Somers Gf and Wilkinson JH.The pharmacological properties of glycyrrhetinicacid-A new anti-inflammatory drug. (J Pharm Pharmacol, 1958,10 (11): 687～695) document shows, glycyrrhizic acid all has no adverse reaction to central nervous system, autonomic nervous system, heart and cardiovascular system.Test with rabbit, normally reach scratch mark and edema and erythema all do not occur, illustrate that glycyrrhizic acid is non-stimulated substantially to the rabbit skin, anxious poison test and subacute toxicity test show that this product toxicity is very low.
The eye drop that contains glycyrrhizic acid dipotassium also has listing in Japan, and concentration is 1%, is used for the treatment of non-infectious eye inflammation.These product are the folk prescription eye drop, only are used for non-infectious eye inflammation, can not be used for inflammation caused by bacterial infection separately.
Summary of the invention
Use the side effect that is produced for fear of steroid at ophthalmology, the present invention uses Radix Glycyrrhizae acids activating agent and antibiotic or Comprecin and excipient composition ophthalmic preparation.Can reach antiinflammatory and antimicrobial effect, avoid the side effect of steroid.Another object of the present invention provides the manufacture method of this compositions and the purposes of this compositions.
The invention provides a kind of ophthalmic composition, it is characterized in that said composition contains: (a) one or more antibiotic or Comprecin; (b) a kind of Radix Glycyrrhizae acids activating agent.
Preferably, described antibiotic or Comprecin are one or more chemical compounds that are selected from down in the group: the salt of tobramycin, neomycin, ofloxacin, levofloxacin, ciprofloxacin, norfloxacin, enoxacin, Gatifloxacin, Moxifloxacin and above-mentioned antimicrobial drug thereof.The salt of above-mentioned antimicrobial drug is meant medically acceptable nontoxic salts, example hydrochloric acid salt, sulfate, lactate, fumarate, citrate, gluconate, glutamate, Glu etc.Preferred example has: Tobramycin Sulfate, hydrochloric acid ofloxacin, lactic acid ofloxacin, levofloxacin hydrochloride, ciprofloxacin, norfloxacin glutamate, Enoxacin Gluconate, methanesulfonic acid Gatifloxacin, Rusuan Jiatishaxing, GATIFLOXACIN, moxifloxacin hydrochloride.
Preferably, described Comprecin is selected from ofloxacin, levofloxacin, ciprofloxacin, Gatifloxacin, Moxifloxacin and their salt thereof.
Preferably, described Comprecin is selected from Gatifloxacin and salt thereof.
Preferably, described Radix Glycyrrhizae acids activating agent is to be selected from: one or more in Radix Glycyrrhizae extractum, glycyrrhizic acid, enoxolone, monopotassium glycyrrhizunate, monoammonium glycyrrhizinate, 18beta-Glycyrrhizic acid monosodium salt, glycyrrhizic acid dipotassium salt, diammonium glycyrhetate, disodium glycyrrhizinate and/or the trisodium glycyrrhetinate salt.
Preferably, described Radix Glycyrrhizae acids activating agent is a glycyrrhizic acid dipotassium salt.
Preferably, described Radix Glycyrrhizae acids active agent content is 0.1～10%.Antibiotic or Comprecin are that ophthalmology receives and effective dose commonly used; The acid-base value of compositions is generally between the receivable pH4 of ophthalmology～9.
Preferably, described Radix Glycyrrhizae acids active agent content is 1～5%.
Preferably, described preparation of compositions treats and/or prevents the application of the topical ophthalmic of eye inflammation and/or eye bacterial infection.
Preferably, the preparation method of described ophthalmic composition together is transformed into a kind of suitable eye dosage form with said composition and at least a liquid or semiliquid carrier or adjuvant.Method for production adopts the conventional method of this area to be made into eye drop, eye ointment, eye emulsifiable paste, gel for eye, instant type gel, eye mask agent, eye pill, ophthalmic intercalating agent.
The invention provides a kind of ophthalmic composition that contains Radix Glycyrrhizae acids activating agent and antibiotic or Comprecin.In this invention, " ophthalmic composition " refers to a kind of medical composition that is used for the treatment of and/or prevents oculopathy, so, ophthalmic preparation of the present invention comprises the preparation with various forms eye topical, as eye drop, eye ointment, eye emulsifiable paste, gel for eye, instant type gel, eye mask agent, eye pill, ophthalmic intercalating agent etc.
The derivant of the Radix Glycyrrhizae acids activating agent that the present invention mentioned and salt thereof are meant medically acceptable, and the chemical compound with anti-inflammatory activity.
The derivant and the salinity thereof of the Radix Glycyrrhizae acids activating agent that the present invention mentioned are 0.1～10%, preferred 1～5%.
The antibiotic that the present invention mentioned is to be had antipathogen or other active class materials by what antibacterial, fungus or other microorganisms produced in life process.The antibiotic that is used to cure the disease except that directly extracting thus, the artificial synthetic method manufacturing of also available synthetic and part and getting.Comprise penicillins, as penicillin sodium salt or potassium salt, ampicillin (sodium ampicillin), piperacillin (avocin), amoxicillin (amoxicillin) etc.; Cephalosporins is as cefalexin (pioneer IV number), cefazolin sodium (Ancef number), cefradine (Ancef I number), ceftriaxone sodium (Ceftriaxone) etc.; Aminoglycosides is as streptomycin, gentamycin, kanamycin, micronomicin (micronomicin), astromicin (Fortimicin) etc.; Tetracyclines is as tetracycline, oxytetracycline, doxycycline (doxycycline) etc.; Chloromycetin, as chloromycetin, thiamphenicol, etc.; Macrolide: erythromycin, Roxithromycin, erythromycin ethylsuccinate, midecamycin, acetylspiramycin, kitasamycin (kitasamycin) etc.The lincomycin class, lincomycin (lincomycin), clindamycin (clindamycin) etc., other main antibacterial antibiotic: norvancomycin, fosfomycin, polymyxin, capreomycin, rifampicin etc.; Antifungal antibiotic: amphotericin B, griseofulvin, cannitracin, nystatin, hachimycin etc.; Antibiotic with immunosuppressive action: ciclosporin etc.More preferably some commonly used antibiotic of ophthalmology: as chloromycetin, chlortetracycline, erythromycin, gentamycin, tobramycin, neomycin etc.
The Comprecin that the present invention mentioned is meant class antibacterials of synthetic, as ofloxacin, levofloxacin, ciprofloxacin, norfloxacin, enoxacin, Gatifloxacin, Moxifloxacin etc., also comprise these compound derivatives and salt, salt is meant medically acceptable nontoxic salts, example hydrochloric acid salt, sulfate, lactate, fumarate, citrate etc.
The antibiotic that the present invention mentioned or the concentration of Comprecin are generally the antimicrobial valid density of folk prescription eye drop, and this concentration will be readily apparent to persons skilled in the art.
The manufacture method that the present invention mentions the ophthalmic composition of Radix Glycyrrhizae acids activating agent and antibiotic or Comprecin is: said composition and at least a liquid or semiliquid carrier or adjuvant together are transformed into a kind of suitable eye dosage form, and method for production adopts the conventional method of this area to be made into eye drop, eye ointment, eye with emulsifiable paste, gel for eye, instant type gel, eye mask agent, a pill, ophthalmic intercalating agent.
Eye drop can contain buffer agent, isotonic agent, antiseptic, stabilizing agent, antioxidant, surfactant, acidity-basicity regulator, chelating agent, absorption enhancer, thickening agent, wetting agent etc.
Buffer agent can be an any compound, as long as they can be adjusted to the receivable pH value of physiology to eye drop; But, preferably live body is not had the chemical compound of side effect at its dosage.The example of buffer agent has bromate buffer, citrate buffer, phosphate buffer, tartrate buffer, acetate buffer, carbonate buffer solution and amino acid salts buffer, borate buffer solution etc.
Isotonic agent comprises and need reach the isotonic saccharide of physiology, salt etc. to eye drop.Saccharide such as sorbitol, mannitol, glucose etc., polyalcohols such as glycerol, propylene glycol, Polyethylene Glycol etc. and salt such as sodium chloride, potassium chloride etc.
Examples of preservatives comprises quaternary ammonium salt such as benzalkonium chloride, benzalkonium bromide, p-Hydroxybenzoate such as methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, sorbic acid and salt thereof, chlorobutanol, chlorhexidine acetate etc.
Thickening agent as hydroxyethyl-cellulose, hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose, carboxy methyl cellulose, CVP Carbopol ETD2050, polyvidone, polyvinyl alcohol, glass acid and salt thereof etc.
Wetting agent can use saccharide and polyalcohols.Saccharide such as mannitol, chondroitin sulfate (and salt), glass acid (and salt) etc.Polyhydric alcohol such as glycerol, Polyethylene Glycol or propylene glycol etc.
Surfactant can be used nonionic, cation, anion and amphoteric surfactant etc.As Tweens, spans, Myrij class, tyloxapol etc.
Antioxidant such as ascorbic acid, sodium ascorbate, vitamin E, sodium thiosulfate, sodium sulfite etc.Chelating agent such as disodium edetate.The example hydrochloric acid of acidity-basicity regulator, citric acid, phosphoric acid, acetic acid, tartaric acid, sodium hydroxide, potassium hydroxide, sodium bicarbonate, boric acid, Borax etc.
Eye pasting substrate can be compositions such as liquid paraffin, lanoline, white vaseline, Yellow Vaselin.
Gel for eye can utilize carbomer, hydroxyethyl-cellulose, hydroxypropyl cellulose, methylcellulose, hydroxypropyl methylcellulose, carboxy methyl cellulose, CVP Carbopol ETD2050, polyvidone, polyvinyl alcohol, glass acid and salt thereof etc. to form gel.
Ophthalmic composition Radix Glycyrrhizae acids active agent content of the present invention is 0.05～10%, preferred 1～5%.Antibiotic or Comprecin are that ophthalmology receives and effective dose commonly used; The acid-base value of compositions is generally between the receivable pH4 of ophthalmology～9.
Compositions of the present invention is used to prepare the ophthalmic preparation that treats and/or prevents eye inflammation and eye bacterial infection.Comprise the ophthalmic preparation that is used for the treatment of and/or prevents outer eye infections such as bacterial conjunctivitis, keratitis, corneal ulcer, dacryocystisis, postoperative infection.
The invention has the beneficial effects as follows that pharmaceutical composition of the present invention can also reduce side effect when can reaching antiinflammatory and antimicrobial effect.
The specific embodiment
Provide following examples to further specify ophthalmic composition of the present invention.But the present invention is not limited thereto.
Embodiment 1
| Title | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 |
| Glycyrrhizic acid dipotassium | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g |
| Gatifloxacin | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Sodium chloride | 0.87g | 0.86g | 0.84g | 0.81g | 0.75g | 0.57g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| Polyoxyethylene sorbitan monoleate | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| HCl or NaOH solution | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 |
| Purified water | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
Preparation method: water intaking is an amount of; Add sodium chloride, disodium edetate, benzalkonium chloride, polyoxyethylene sorbitan monoleate, glycyrrhizic acid dipotassium, Gatifloxacin dissolving, moisturizing is to total amount, and hydrochloric acid or sodium hydroxide solution are transferred pH to 7.0～7.4, and circulation steam sterilization 30 minutes divides to be filled in the plastics eye-drop liquid bottle.
Embodiment 2
| Prescription 7 | Prescription 8 | Prescription 9 | Prescription 10 | Prescription 11 | Prescription 12 | |
| Glycyrrhizic acid dipotassium | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g |
| Gatifloxacin | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Hyaluronic acid sodium | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| Glycerol | 2.55g | 2.52g | 2.47g | 2.38g | 1.68g | 2.20g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| HCl or NaOH solution | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 |
| Purified water | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
Preparation method: get hyaluronic acid sodium and be dissolved in the part water heating for dissolving; Water intaking is an amount of in addition, adds glycerol, disodium edetate, benzalkonium chloride, glycyrrhizic acid dipotassium, Gatifloxacin dissolving; Above-mentioned two kinds of solution are mixed, and moisturizing is to total amount, circulation steam sterilization 30 minutes, and hydrochloric acid or sodium hydroxide solution are transferred pH to 7.0～7.4, divide to be filled in the plastics eye-drop liquid bottle.
Embodiment 3
| Prescription 13 | Prescription 14 | Prescription 15 | Prescription 16 | Prescription 17 | Prescription 18 | |
| Glycyrrhizic acid dipotassium | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g |
| Moxifloxacin | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Hyaluronic acid sodium | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| Sodium chloride | 0.87g | 0.86g | 0.84g | 0.81g | 1.68g | 0.57g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| Polyoxyethylene sorbitan monoleate | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| HCl or NaOH solution | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 |
| Purified water | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
Preparation method: get hyaluronic acid sodium and be dissolved in the part water heating for dissolving; Water intaking is an amount of in addition, adds sodium chloride, disodium edetate, benzalkonium chloride, polyoxyethylene sorbitan monoleate, glycyrrhizic acid dipotassium, Moxifloxacin dissolving; Above-mentioned two kinds of solution are mixed, and moisturizing is to total amount, and hydrochloric acid or sodium hydroxide solution are transferred pH to 7.0～7.4, and circulation steam sterilization 30 minutes divides to be filled in the plastics eye-drop liquid bottle.
Embodiment 4
| Prescription 19 | Prescription 20 | Prescription 21 | Prescription 22 | Prescription 23 | Prescription 24 | |
| Glycyrrhizic acid dipotassium | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g |
| Levofloxacin hydrochloride | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Hyaluronic acid sodium | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| Sodium chloride | 0.87g | 0.86g | 0.84g | 0.81g | 1.68g | 0.57g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| Polyoxyethylene sorbitan monoleate | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| HCl or NaOH solution | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 |
| Purified water | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
Preparation method: get hyaluronic acid sodium and be dissolved in the part water heating for dissolving; Water intaking is an amount of in addition, adds sodium chloride, disodium edetate, benzalkonium chloride, polyoxyethylene sorbitan monoleate, glycyrrhizic acid dipotassium, levofloxacin hydrochloride dissolving; Above-mentioned two kinds of solution are mixed, and moisturizing is to total amount, and hydrochloric acid or sodium hydroxide solution are transferred pH to 7.0～7.4, and circulation steam sterilization 30 minutes divides to be filled in the plastics eye-drop liquid bottle.
Embodiment 5
| Prescription 25 | Prescription 26 | Prescription 27 | Prescription 28 | Prescription 29 | Prescription 30 | |
| Glycyrrhizic acid | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g |
| Ofloxacin | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Hyaluronic acid sodium | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| Sodium chloride | 0.87g | 0.86g | 0.84g | 0.81g | 1.68g | 0.57g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| Polyoxyethylene sorbitan monoleate | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| HCl or NaOH solution | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 |
| Purified water | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
Preparation method: get hyaluronic acid sodium and be dissolved in the part water; Water intaking is an amount of in addition, adds sodium chloride, disodium edetate, benzalkonium chloride, polyoxyethylene sorbitan monoleate, glycyrrhizic acid dipotassium, ofloxacin dissolving; Above-mentioned two kinds of solution are mixed, and moisturizing is to total amount, and hydrochloric acid or sodium hydroxide solution are transferred pH to 7.0～7.4, and circulation steam sterilization 30 minutes divides to be filled in the plastics eye-drop liquid bottle.
Embodiment 6
| Prescription 31 | Prescription 32 | Prescription 33 | Prescription 34 | Prescription 35 | Prescription 36 | |
| Glycyrrhizic acid list potassium | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g |
| Tobramycin | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Hyaluronic acid sodium | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| Sodium chloride | 0.87g | 0.86g | 0.84g | 0.81g | 1.68g | 0.57g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| Polyoxyethylene sorbitan monoleate | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| HCl or NaOH solution | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 |
| Purified water | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
Preparation method: get hyaluronic acid sodium and be dissolved in the part water; Water intaking is an amount of in addition, adds sodium chloride, disodium edetate, benzalkonium chloride, polyoxyethylene sorbitan monoleate, glycyrrhizic acid dipotassium, tobramycin dissolving; Above-mentioned two kinds of solution are mixed, and moisturizing is to total amount, and hydrochloric acid or sodium hydroxide solution are transferred pH to 7.0～7.4, and circulation steam sterilization 30 minutes divides to be filled in the plastics eye-drop liquid bottle.
Embodiment 7
| Prescription 37 | Prescription 38 | Prescription 39 | Prescription 40 | Prescription 41 | Prescription 42 | |
| Disodium glycyrrhizinate | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g |
| Gatifloxacin | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Acritamer 940 | 0.5g | 0.5g | 0.5g | 0.5g | 0.5g | 0.5g |
| Glycerol | 2.55g | 2.52g | 2.47g | 2.38g | 1.68g | 2.20g |
| Hyaluronic acid sodium | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| HCl or NaOH solution | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 | Transfer pH7.0～7.4 |
| Purified water | Add to 100g | Add to 100g | Add to 100g | Add to 100g | Add to 100g | Add to 100g |
Preparation method: get Acritamer 940 and hyaluronic acid sodium and be dissolved in the part water; Water intaking is an amount of in addition, adds glycerol, disodium edetate, benzalkonium chloride, glycyrrhizic acid dipotassium, Gatifloxacin dissolving; Above-mentioned two kinds of solution are mixed, and moisturizing is to total amount, and hydrochloric acid or sodium hydroxide solution are transferred pH to 7.0～7.4, and circulation steam sterilization 30 minutes divides to be filled in the aluminum pipe, gets gel for eye use.
Embodiment 8
| Prescription 43 | Prescription 44 | Prescription 45 | Prescription 46 | Prescription 47 | Prescription 48 | Prescription 49 | |
| Diammonium glycyrrhizinate | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g | 10g |
| Gatifloxacin | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Sodium chloride | 0.87g | 0.86g | 0.84g | 0.81g | 0.75g | 0.57g | 0.57g |
| HCl or NaOH solution | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 | Transfer pH=7.0～7.4 |
| Purified water | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
Preparation method: water intaking is an amount of; Add sodium chloride, glycyrrhizic acid dipotassium, Gatifloxacin dissolving, moisturizing is to total amount, and hydrochloric acid or sodium hydroxide solution were transferred pH to 7.0～7.4,115 ℃ steam sterilization 30 minutes, divided to be filled in the disposable plastic eye-drop liquid bottle.
Embodiment 9: zoopery:
1. test material
Test sample FD01-FD14, the eye drop compound preparation.Provide by Baushe ﹠ Lomb-Fu Ruida pharmaceutical Co. Ltd.The prescription of FD01-FD14 is as follows, and its preparation method is with embodiment 1.
| Title | Matched group | FD01 | FD02 | FD03 | FD04 | FD05 | FD06 | FD07 |
| Glycyrrhizic acid dipotassium | - | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g | - |
| Gatifloxacin | - | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Sodium chloride | 0.90g | 0.87g | 0.86g | 0.84g | 0.81g | 0.75g | 0.57g | 0.57g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| Polyoxyethylene sorbitan monoleate | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| HCl or NaOH solution | Transfer pH7.0～7.4 | |||||||
| Purified water | Add to 100ml | |||||||
| FD08 | FD09 | FD010 | FD011 | FD012 | FD013 | FD014 | |
| Glycyrrhizic acid dipotassium | 0.05g | 0.2g | 0.5g | 1g | 2g | 5g | - |
| Levofloxacin hydrochloride | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g | 0.3g |
| Hyaluronic acid sodium | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| Sodium chloride | 0.87g | 0.86g | 0.84g | 0.81g | 1.68g | 0.57g | 0.57g |
| Disodium edetate | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g | 0.02g |
| Benzalkonium chloride | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g | 0.01g |
| Polyoxyethylene sorbitan monoleate | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g | 0.1g |
| HCl or NaOH solution | Transfer pH7.0～7.4 | ||||||
| Purified water | Add to 100ml | ||||||
2. to the protective effect of rabbit ocular injury
(1), modeling
Get 72 of new zealand rabbits, male and female are not limit, healthy no oculopathy.Auricular vein is injected pentobarbital sodium 30mg/kg anesthesia.With diameter 9mm circular filter paper, infiltration 1mol/L sodium hydroxide sticks in the rabbit cornea central area, takes off filter paper behind the 30sec, with normal saline flushing lagophthalmos 2min.
(2), test grouping
Behind the modeling 24h, carry out the fluorescent staining inspection with slit lamp, observe each animal cornea, iris and conjunctiva the irritant reaction situation and keep the score.According to the reaction score value 72 rabbit are divided into 4 groups at random, promptly FD01～FD014 organizes, 3 every group.
(3), medication
New zealand rabbit is fixed with holder, draws back rabbit left side eyelid, then eye drop is splashed in the conjunctiva of left eye capsule, and 2 of successive administrations give behind the medicine about 10 seconds of the passive closure of the eyelid of rabbit in order to avoid medicine flows out.Right eye gives same medicine with method.Every day 1 time, each 2, continuous 5 days.
(4), observation index and result judge
After 24h and the last administration rabbit eyes are carried out gross examination of skeletal muscle after the modeling, and eye carried out the fluorescent staining inspection with slit lamp, and press the eye irritant test standards of grading and mark, and the reaction score value addition of cornea, iris and the conjunctiva of each animal got total mark, every group total mark divided by number of animals, is got mean scores.Judge that being tried the thing eye improves degree.
A. gross examination of skeletal muscle
24h after the modeling, all animal eyes open difficulty, photophobia, tear and discharge of eye showed increased.After the last administration, except that model control group, all the other each treated animal eyes inflammatory reactions all are improvement in various degree, and discharge of eye obviously reduces.
B. slit lamp examination
24h after the modeling, all animal conjunctiva of both eyes, iris hyperemia, edema, secretions increase are found in the row slit lamp examination, indivedual iris details are unclear; The corneal opacity, ulcer, the reaction integration is all more than 13 minutes, belong to the intensity irritative response, 5d after the administration, except that model control group, all the other each treated animal eyes inflammatory reaction all are improvement in various degree, and the corneal ulcer wound surface obviously reduces, conjunctiva, iris hyperemia, edema alleviate, and secretions reduces.The reaction integration all is lower than 9, belongs to slight irritative response.Experimental data sees Table 1.
5 days inflammatory reaction eyes of table 1 rabbit medication 0 day and medication stimulate integral recording table
| 0d | 5d | |
| Matched group | 14 | 13 |
| FD01 | 14 | 11 |
| FD02 | 14 | 8 |
| FD03 | 13 | 8 |
| FD04 | 13 | 7 |
| FD05 | 13 | 6 |
| FD06 | 14 | 6 |
| FD07 | 14 | 9 |
| FD08 | 14 | 11 |
| FD09 | 13 | 8 |
| FD010 | 13 | 8 |
| FD011 | 13 | 7 |
| FD012 | 14 | 6 |
| FD013 | 13 | 6 |
| FD014 | 13 | 6 |
3. conclusion (of pressure testing)
The compound eye drops of the glycyrrhizic acid dipotassium of adding 0.05%～5% has better antiinflammatory action than the antibiotic eye drop of folk prescription, and raises with concentration, and antiinflammatory action is also stronger.
Embodiment 10: external bacteriostasis
1. test method
(1), diluted sample: adopt double dilution method with the MH broth bouillon with the Yinzhihuang oral liquid two-fold dilution, establish stock solution, 1: 2,1: 4,1: 8,1: 16,1: 32 and 1: 64 successively, establish positive growth control pipe simultaneously, put 1ml/ pipe in the magnificent test tube of sterilization.
(2), add bacterium liquid: add the corresponding bacterium liquid 0.1ml for preparing in each row, each pipe is shaken up.
(3), cultivate: test sample, positive control, negative control are put into 37 ℃ of incubators together cultivate 48h, after the taking-up with staphylococcus aureus and pneumococcal culture fluid dibbling blood agar plate, it is the MIC of this sample with the high dilution of asepsis growth that other dibbling nutrient agar panels, 37 ℃ of 24h are cultivated the back.Positive control is answered well-grown, and negative control is answered asepsis growth.
2. result of the test
The antimicrobial drug folk prescription eye drop FD07 sample that tries was respectively 1: 32,1: 64,1: 32 and 1: 64 Klebsiella pneumonia, escherichia coli, staphylococcus aureus, pneumococcal MIC, and the FD06 sample that tries was respectively 1: 32,1: 34,1: 32 and 1: 64 Klebsiella pneumonia, escherichia coli, staphylococcus aureus, pneumococcal MIC.
3. conclusion (of pressure testing)
5% glycyrrhizic acid dipotassium does not disturb antimicrobial drug to Klebsiella pneumonia, escherichia coli, staphylococcus aureus, pneumococcal bacteriostasis.
Claims (10)
1. an ophthalmic composition is characterized in that said composition contains: (a) one or more antibiotic or Comprecin; (b) a kind of Radix Glycyrrhizae acids activating agent.
2. ophthalmic composition as claimed in claim 1, it is characterized in that described antibiotic or Comprecin are one or more chemical compounds that are selected from down in the group: the salt of tobramycin, neomycin, ofloxacin, levofloxacin, ciprofloxacin, norfloxacin, enoxacin, Gatifloxacin, Moxifloxacin and above-mentioned antimicrobial drug thereof.
3. ophthalmic composition as claimed in claim 1 is characterized in that described Comprecin is selected from ofloxacin, levofloxacin, ciprofloxacin, Gatifloxacin, Moxifloxacin and salt thereof.
4. ophthalmic composition as claimed in claim 1 is characterized in that described Comprecin is selected from Gatifloxacin and salt thereof.
5. as claim 1 or 3 described ophthalmic compositions, it is characterized in that described Radix Glycyrrhizae acids activating agent is to be selected from: one or more in Radix Glycyrrhizae extractum, glycyrrhizic acid, enoxolone, monopotassium glycyrrhizunate, monoammonium glycyrrhizinate, 18beta-Glycyrrhizic acid monosodium salt, glycyrrhizic acid dipotassium salt, diammonium glycyrhetate, disodium glycyrrhizinate and/or the trisodium glycyrrhetinate salt.
6. as each described ophthalmic composition of claim 1 to 4, it is characterized in that described Radix Glycyrrhizae acids activating agent is a glycyrrhizic acid dipotassium salt.
7. ophthalmic composition as claimed in claim 1 is characterized in that, described Radix Glycyrrhizae acids active agent content is 0.05～10%.
8. ophthalmic composition as claimed in claim 1 is characterized in that, described Radix Glycyrrhizae acids active agent content is 1～5%.
9. the application of ophthalmic composition as claimed in claim 1 is characterized in that, described preparation of compositions treats and/or prevents the application of the topical ophthalmic of eye inflammation and/or eye bacterial infection.
10. the preparation method of ophthalmic composition as claimed in claim 1 is characterized in that: said composition and at least a liquid or semiliquid carrier or adjuvant together are transformed into a kind of suitable eye dosage form.
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| CN102366317A (en) * | 2011-10-21 | 2012-03-07 | 大连创达技术交易市场有限公司 | Eye-protection wet tissue |
| EP2526923A1 (en) * | 2009-11-27 | 2012-11-28 | Shenyang Xingqi Pharmaceutical Co., Ltd. | Ophthalmic gel of gatifloxacin and preparation method thereof |
| CN103565816A (en) * | 2012-07-25 | 2014-02-12 | 天津金耀集团有限公司 | Tobramycin-dexamethasone eye drops |
| CN110179748A (en) * | 2019-06-25 | 2019-08-30 | 吉林省华恩生物科技有限公司 | A kind of alleviation inflammation of eye section and allergic symptom eye drops and preparation method thereof |
| CN111228034A (en) * | 2020-01-16 | 2020-06-05 | 贵州省人民医院 | Drug-loading controlled-release lacrimal duct embolus and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP3450805B2 (en) * | 2000-08-08 | 2003-09-29 | わかもと製薬株式会社 | Aqueous pharmaceutical composition |
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- 2007-08-07 CN CN200710015197A patent/CN101130083B/en not_active Expired - Fee Related
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| EP2526923A1 (en) * | 2009-11-27 | 2012-11-28 | Shenyang Xingqi Pharmaceutical Co., Ltd. | Ophthalmic gel of gatifloxacin and preparation method thereof |
| EP2526923A4 (en) * | 2009-11-27 | 2014-03-12 | Shenyang Xingqi Pharmaceutical Co Ltd | Ophthalmic gel of gatifloxacin and preparation method thereof |
| CN102366317A (en) * | 2011-10-21 | 2012-03-07 | 大连创达技术交易市场有限公司 | Eye-protection wet tissue |
| CN103565816A (en) * | 2012-07-25 | 2014-02-12 | 天津金耀集团有限公司 | Tobramycin-dexamethasone eye drops |
| CN110179748A (en) * | 2019-06-25 | 2019-08-30 | 吉林省华恩生物科技有限公司 | A kind of alleviation inflammation of eye section and allergic symptom eye drops and preparation method thereof |
| CN111228034A (en) * | 2020-01-16 | 2020-06-05 | 贵州省人民医院 | Drug-loading controlled-release lacrimal duct embolus and preparation method thereof |
| CN111265513A (en) * | 2020-02-06 | 2020-06-12 | 河北农业大学 | Application of traditional Chinese medicine monomer in preparation of bacterial efflux pump inhibitor or drug for improving antibiotic activity and combined bacteriostatic composition |
| RU2780109C1 (en) * | 2022-01-26 | 2022-09-19 | федеральное государственное автономное образовательное учреждение высшего образования "Казанский (Приволжский) федеральный университет" (ФГАОУ ВО КФУ) | Anti-inflammatory eye drops for pets and farm animals |
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| CN101130083B (en) | 2010-05-19 |
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