CN116687841A - Eye drops of pemirolast potassium and preparation method thereof - Google Patents
Eye drops of pemirolast potassium and preparation method thereof Download PDFInfo
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- CN116687841A CN116687841A CN202210185077.5A CN202210185077A CN116687841A CN 116687841 A CN116687841 A CN 116687841A CN 202210185077 A CN202210185077 A CN 202210185077A CN 116687841 A CN116687841 A CN 116687841A
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- Prior art keywords
- pemirolast potassium
- eye drop
- pemirolast
- potassium
- injection
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- 229960004811 pemirolast potassium Drugs 0.000 title claims abstract description 75
- NMMVKSMGBDRONO-UHFFFAOYSA-N potassium;9-methyl-3-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound [K+].CC1=CC=CN(C2=O)C1=NC=C2C1=NN=N[N-]1 NMMVKSMGBDRONO-UHFFFAOYSA-N 0.000 title claims abstract description 75
- 239000003889 eye drop Substances 0.000 title claims abstract description 63
- 229940012356 eye drops Drugs 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000008215 water for injection Substances 0.000 claims abstract description 37
- 230000003204 osmotic effect Effects 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 58
- 239000011259 mixed solution Substances 0.000 claims description 32
- 229920003081 Povidone K 30 Polymers 0.000 claims description 29
- 239000011780 sodium chloride Substances 0.000 claims description 29
- 238000002156 mixing Methods 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 17
- 238000004806 packaging method and process Methods 0.000 claims description 17
- 230000001954 sterilising effect Effects 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 17
- 238000001816 cooling Methods 0.000 claims description 16
- 238000010438 heat treatment Methods 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- 235000011187 glycerol Nutrition 0.000 claims description 5
- 230000001105 regulatory effect Effects 0.000 claims description 5
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 4
- 239000004327 boric acid Substances 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 3
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- -1 hydroxypropyl ethylcellulose Chemical compound 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- LEAHFJQFYSDGGP-UHFFFAOYSA-K trisodium;dihydrogen phosphate;hydrogen phosphate Chemical compound [Na+].[Na+].[Na+].OP(O)([O-])=O.OP([O-])([O-])=O LEAHFJQFYSDGGP-UHFFFAOYSA-K 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 1
- 235000010338 boric acid Nutrition 0.000 claims 1
- 239000000872 buffer Substances 0.000 claims 1
- 239000007979 citrate buffer Substances 0.000 claims 1
- 235000001727 glucose Nutrition 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 1
- 229940069328 povidone Drugs 0.000 claims 1
- 235000002639 sodium chloride Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 12
- 206010067484 Adverse reaction Diseases 0.000 abstract description 6
- 230000006838 adverse reaction Effects 0.000 abstract description 6
- 239000000243 solution Substances 0.000 abstract description 4
- 230000002035 prolonged effect Effects 0.000 abstract description 2
- 238000010521 absorption reaction Methods 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 229960004439 pemirolast Drugs 0.000 description 18
- HIANJWSAHKJQTH-UHFFFAOYSA-N pemirolast Chemical compound CC1=CC=CN(C2=O)C1=NC=C2C=1N=NNN=1 HIANJWSAHKJQTH-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 13
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 12
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 12
- 235000019799 monosodium phosphate Nutrition 0.000 description 12
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 12
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 8
- 208000002205 allergic conjunctivitis Diseases 0.000 description 8
- 208000024998 atopic conjunctivitis Diseases 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000007794 irritation Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 206010039085 Rhinitis allergic Diseases 0.000 description 4
- 201000010105 allergic rhinitis Diseases 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- 206010012438 Dermatitis atopic Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 201000008937 atopic dermatitis Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 2
- 206010010741 Conjunctivitis Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 206010052140 Eye pruritus Diseases 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010041349 Somnolence Diseases 0.000 description 2
- 239000002318 adhesion promoter Substances 0.000 description 2
- 201000009961 allergic asthma Diseases 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000000744 eyelid Anatomy 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 206010010726 Conjunctival oedema Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000006069 Corneal Opacity Diseases 0.000 description 1
- 206010051559 Corneal defect Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 208000009847 Eye Foreign Bodies Diseases 0.000 description 1
- 206010015946 Eye irritation Diseases 0.000 description 1
- 206010016825 Flushing Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010023644 Lacrimation increased Diseases 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000003915 air pollution Methods 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 208000010217 blepharitis Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 231100000269 corneal opacity Toxicity 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 231100000013 eye irritation Toxicity 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000004317 lacrimation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004175 meibomian gland Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000007981 phosphate-citrate buffer Substances 0.000 description 1
- 229940043274 prophylactic drug Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 201000003826 superficial keratitis Diseases 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to an eye drop containing pemirolast potassium, belonging to the technical field of pharmaceutical preparations. The eye drop disclosed by the invention contains pemirolast potassium, a viscosity increasing agent, a pH regulator, an osmotic pressure regulator and water for injection. The eye drops prepared by the invention are in a solution state, so that the eye drops are comfortable and have less adverse reaction; the viscosity of the eye drops is properly increased by the viscosity increasing agent, so that the residence time of the medicine in eyes is prolonged, the medicine absorption is increased, and the bioavailability is improved; the administration frequency is reduced, and the patient compliance is improved.
Description
Technical Field
The invention belongs to the technical field of medicinal preparations, and in particular relates to an eye drop of pemirolast potassium and a preparation method thereof.
Background
Pemirolast potassium is a drug that was first developed by the company schnobiletin in the united states to inhibit the release of antigen-induced allergic mediators in the united states in 1977, and was mainly used in the early clinical stages for the treatment of asthma, and was marketed in japan by BMS in 1991 under pemirolast (trade name) and Mitsubishi-TOKYO in Alegysal (trade name); in 1993, alegysal was marketed in Japan as a drug for treating allergic conjunctivitis; an indication of increased allergic rhinitis in 1994; pemirolast potassium eye drops (trade name: alamast) were approved by the FDA of 24 th Japan, 9 th 1999, and marketed; day 1, 5, 2000, approval Pemirolast potassium was marketed as a prophylactic and therapeutic drug for atopic dermatitis. At present, tablets and eye drops are marketed at home and abroad in succession and are used for treating diseases such as allergic asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis and the like.
The pemirolast potassium eye drops have the effect of inhibiting allergic conjunctivitis, and are suitable for treating allergic conjunctivitis and catarrhal conjunctivitis in spring. With the development of modern industry, air pollution is increasingly serious, and external harmful substances (such as harmful gases, dust, sensitized microorganisms, sensitized allergens and the like) are continuously increased, so that the morbidity and mortality of various allergic diseases are increased, and the illness state and the etiology are more complex. It is counted that up to 25% of the people worldwide today suffer from different types of allergic diseases (mainly allergic asthma, allergic rhinitis, allergic skin diseases, allergic eye diseases, etc.). The Chinese is the first people in the world, the environmental pollution degree is increasingly serious, the population suffering from the diseases is continuously enlarged, and the demand for the medicines is also continuously increased.
Allergic conjunctivitis is a common disease of eyes, is an allergic reaction of conjunctiva of eyes to external or endogenous mutagens, patients have ocular symptoms such as ocular itching, congestion and the like which are difficult to tolerate, common vasoconstrictors or corticosteroids can be used for acute-phase treatment, and 4% cromolyn sodium can be used for eye drops, but adverse reactions of the whole body and local parts of the drugs are common. Therefore, an ideal drug for treating allergic conjunctivitis should be a safe and eye-friendly drug. The pemirolast potassium eye drops are novel mast cell membrane stabilizers, and can be obviously effective only by 0.1%, so that adverse reactions are less. The pemirolast potassium is taken as a strong, long-acting and safe drug for preventing and treating variant asthma, allergic rhinitis, allergic conjunctivitis and atopic dermatitis, and the clinical prospect is consistent and good.
Disclosure of Invention
The following common adverse reactions exist due to the clinically used pemirolast potassium tablets: sleepiness, drowsiness, headache of the related central nervous system, nausea, vomiting, stomatitis, gastralgia, abdominal pain, constipation, diarrhea, thirst, dyspepsia, soft stool of the related digestive system, platelet increase of the related blood lineage, hemoglobin decrease, etc. In addition, allergic reactions such as rash, urticaria, facial flushing and the like may also occur when pemirolast potassium tablets are taken.
On one hand, the pemirolast potassium eye drops provided by the invention contain pemirolast potassium, a viscosity increasing agent, a pH regulator, an osmotic pressure regulator and water for injection, and do not contain any bacteriostat.
The viscosity increaser is methyl cellulose, polyvinyl alcohol, polyethylene glycol, povidone K30, hydroxypropyl ethyl cellulose and the like.
Preferably, the viscosity increasing agent in the pemirolast potassium eye drop is povidone K30.
The pH regulator is at least one of boric acid, borate buffer solution, phosphate buffer solution and citrate buffer solution.
Preferably, the pH regulator is sodium dihydrogen phosphate-disodium hydrogen phosphate buffer.
More preferably, the amount of the pH regulator is based on the pH value of the eye drops regulated to 6.5-8.5; more preferably, the amount is such that the pH of the eye drop is adjusted to 7.0 to 8.0.
Preferably, the osmotic pressure regulator is at least one of sodium chloride, potassium chloride, boric acid, glucose and glycerol.
More preferably, the osmolality adjusting agent is sodium chloride.
The dosage of the osmotic pressure regulator is based on regulating the molar concentration ratio of the osmotic pressure to be 0.7-0.9.
The invention eliminates the use of bacteriostat, and long-term use of eye drops containing bacteriostat (mainly benzalkonium chloride) can cause eye foreign body sensation, burning irritation, dryness sensation, lacrimation, eye itching and other eye surface symptoms, conjunctival congestion, conjunctival follicular, superficial keratitis, blepharitis, meibomian gland inflammation and eyelid eczema. The eye drop contains no antibacterial agent, and is convenient to carry in single dose package. The purpose of controlling the dosage of the medicine can be achieved by controlling the dosage of single dosage.
In order to reduce adverse reactions of the pemirolast potassium and improve the curative effect, the prescription is optimized according to the physicochemical properties of the pemirolast potassium, and the pemirolast potassium eye drop with more remarkable curative effect is provided.
The invention optimizes the weight proportion of four components of the pemirolast potassium, the adhesion promoter, the pH regulator and the osmotic pressure regulator.
Preferably, each 100ml of the pemirolast potassium eye drop comprises four components of pemirolast potassium, a viscosity increasing agent, a pH regulator and an osmotic pressure regulator in parts by weight:
more preferably, each 100ml of the pemirolast potassium eye drop comprises four components by weight:
further preferably, each 100ml of pemirolast potassium eye drop comprises four components by weight:
on the other hand, the preparation method of the pemirolast potassium eye drop provided by the invention specifically comprises the following steps:
stirring and dissolving a prescription amount of viscosity increasing agent and osmotic pressure regulator by using a proper amount of water for injection to obtain a mixed solution;
adding a pH regulator, regulating the pH of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature;
adding primisulfite potassium with the prescription amount, uniformly mixing, adding water for injection to the full amount, filtering, sterilizing, and aseptically packaging.
The invention selects the optimal dosage of the adhesion promoter, the pH regulator and the osmotic pressure regulator, can lighten the irritation of eye drops to eye tissue cells, reduce the uncomfortable feeling of patients and effectively exert the drug effect; in addition, the retention time of the medicine in eyes can be prolonged, and the curative effect of the medicine can be improved.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
In order to better illustrate the present invention, further examples are provided below.
Example 1
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 2
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
adding a prescribed amount of polyvinyl alcohol into 80ml of water for injection, stirring and dissolving, adding sodium chloride, and uniformly mixing to obtain a mixed solution; adjusting the pH of the mixed solution to 7.5 by using 2% sodium hydroxide solution, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 3
The present example provides a pemirolast potassium eye drop, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
adding a prescribed amount of polyvinyl alcohol into 80ml of water for injection, stirring for dissolution, adding glycerol, and uniformly mixing to obtain a mixed solution; adding the citric acid and the sodium citrate with the prescribed amounts, adjusting the pH of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 4
The present example provides a pemirolast potassium eye drop, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and the glycerol with the prescription amount, adding the povidone K30 and the glycerol into 80ml of water for injection, stirring and dissolving the components, and uniformly mixing the components to obtain a mixed solution; adding sodium dihydrogen phosphate and disodium hydrogen phosphate with the prescribed amounts, adjusting pH to 7.5, heating at 100deg.C for 30 min, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 5
The present example provides a pemirolast potassium eye drop, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, stirring and dissolving the mixture, and uniformly mixing the mixture to obtain a mixed solution; adding the citric acid and the sodium citrate with the prescribed amounts, adjusting the pH to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 6
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 6.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 7
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 7.0, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 8
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 8.0, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 9
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 8.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Example 10
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Comparative example 1
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Comparative example 2
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Comparative example 3
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Comparative example 4
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30 and sodium chloride with the prescribed amounts, adding the povidone K30 and the sodium chloride into 80ml of water for injection, and stirring and dissolving the mixture to obtain a mixed solution; adding the sodium dihydrogen phosphate and the disodium hydrogen phosphate with the prescribed amounts, adjusting the pH value of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding the pemirolast potassium with the prescription amount, uniformly mixing, adding the water for injection to the total volume of 100ml, filtering, sterilizing, and aseptically packaging to obtain the pemirolast.
Comparative example 5
The embodiment provides pemirolast potassium eye drops, the prescription dosage of which is shown in the following table:
the preparation method comprises the following steps:
taking the povidone K30, sodium chloride and pemirolast potassium with the prescription amount, adding the povidone K30, sodium chloride and pemirolast potassium into 80ml of water for injection, stirring and dissolving to obtain a mixed solution; adding sodium dihydrogen phosphate and disodium hydrogen phosphate with the prescribed amounts, regulating the pH of the mixed solution to 7.5, mixing uniformly, adding water for injection to 100ml of the total amount, filtering, sterilizing, and packaging under aseptic condition.
Eye drop stability test
100 bottles of pemirolast potassium eye drops prepared in examples 1 to 10 and comparative examples 1 to 5 were randomly extracted, placed under conditions of (30+ -2) deg.C and relative humidity of (35+ -5)%, and placed for 24 months, and sampled for 0 month, 3 months, 6 months, 9 months, 12 months, 18 months and 24 months, respectively, and tested according to stability emphasis examination items. The test results show that the pemirolast potassium eye drops prepared in examples 1-10 and comparative example 1.5 of the present invention can be stably stored for at least 24 months under the conditions of pH of 7.0-8.0, temperature of (30+ -2) deg.C and relative humidity of (35+ -5)%. Stability study the results are shown in table 1.
Table 1 stability investigation test results
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Eye drop irritation test
The safety of the pemirolast potassium eye drop formulation was examined with the samples prepared in examples 1 to 10 and comparative examples 1 to 5. The irritation test of single administration and multiple administration to rabbit eyes was observed. Each rabbit was examined for eyes before the test, and rabbits without eye irritation, corneal defect, and conjunctival damage were selected. 24 healthy rabbits were randomly divided into 8 groups. The left eye drops pemirolast potassium eye drops and the right eye drops an equal amount of sterile injectable water, and then the eyelid is gently closed for about 10s. The eye local reaction conditions of 0h, 12h, 24h, 48h and 72h after administration were observed by taking corneal opacity, iris hyperemia, conjunctival edema, conjunctival hyperemia and conjunctival secretion as examination indexes, and the test results are shown in Table 2.
TABLE 2 results of the irritation test
The results of the test example show that the pemirolast potassium eye drop product has no irritation and damage to eyes, is suitable for treating allergic conjunctivitis and spring catarrhal conjunctivitis, has good treatment effect and less adverse reaction, and has wide market popularization prospect.
Claims (10)
1. The pemirolast potassium eye drop is characterized by mainly comprising pemirolast potassium, a viscosity increasing agent, a pH regulator, an osmotic pressure regulator and water for injection.
2. The pemirolast potassium eye drop of claim 1, wherein each 100ml of the pemirolast potassium eye drop comprises four components by weight:
3. the pemirolast potassium eye drop of claim 2, wherein each 100ml of the pemirolast potassium eye drop comprises four components by weight:
4. the pemirolast potassium eye drop of claim 3, wherein each 100ml of the pemirolast potassium eye drop comprises four components by weight:
5. the pemirolast potassium eye drop of claim 1, wherein the viscosity increasing agent is methylcellulose, polyvinyl alcohol, polyethylene glycol, povidone, hydroxypropyl ethylcellulose; povidone K30 is preferred.
6. The pemirolast potassium eye drop of claim 1, wherein the pH adjuster is at least one of boric acid, borate buffer, phosphate buffer, citrate buffer; sodium dihydrogen phosphate-disodium hydrogen phosphate buffer is preferred.
7. The pemirolast potassium eye drop of claim 1, wherein the osmotic pressure regulator is at least one of sodium chloride, potassium chloride, boric acid, glucose, and glycerin; sodium chloride is preferred.
8. The pemirolast potassium eye drop of claim 1, wherein the osmolality adjusting agent is used in an amount to adjust the osmolality ratio to 0.7 to 0.9.
9. The pemirolast potassium eye drop of claim 1, wherein the pH adjustor is used in an amount to adjust the pH of the eye drop to 6.5 to 8.5; preferably 7.0 to 8.0.
10. A process for the preparation of pemirolast potassium eye drops as claimed in any one of claims 1 to 9, wherein said process comprises the steps of: stirring and dissolving a prescription amount of viscosity increasing agent and osmotic pressure regulator by using a proper amount of water for injection to obtain a mixed solution; adding a pH regulator, regulating the pH of the mixed solution to 7.5, heating at 100 ℃ for 30 minutes, and cooling to room temperature; adding primisulfite potassium with the prescription amount, uniformly mixing, adding water for injection to the full amount, filtering, sterilizing, and aseptically packaging.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202210185077.5A CN116687841A (en) | 2022-02-28 | 2022-02-28 | Eye drops of pemirolast potassium and preparation method thereof |
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| CN202210185077.5A CN116687841A (en) | 2022-02-28 | 2022-02-28 | Eye drops of pemirolast potassium and preparation method thereof |
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