CN117599054B - Pharmaceutical composition for treating pseudomyopia and application thereof - Google Patents
Pharmaceutical composition for treating pseudomyopia and application thereof Download PDFInfo
- Publication number
- CN117599054B CN117599054B CN202410096928.8A CN202410096928A CN117599054B CN 117599054 B CN117599054 B CN 117599054B CN 202410096928 A CN202410096928 A CN 202410096928A CN 117599054 B CN117599054 B CN 117599054B
- Authority
- CN
- China
- Prior art keywords
- anisodine
- hydrobromide
- pseudomyopia
- pharmaceutical composition
- eye drops
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000004436 pseudomyopia Effects 0.000 title claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- 239000003889 eye drop Substances 0.000 claims abstract description 35
- 229940012356 eye drops Drugs 0.000 claims abstract description 22
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 9
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 16
- GJPDCORRBGIJOP-HTCOGKIYSA-N anisodine hydrobromide Chemical compound Br.C1([C@](O)(CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@H]2[C@@H]3O2)C)=CC=CC=C1 GJPDCORRBGIJOP-HTCOGKIYSA-N 0.000 claims description 15
- 239000003885 eye ointment Substances 0.000 claims description 3
- 229960005174 ambroxol Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940100655 ophthalmic gel Drugs 0.000 claims 1
- 229940023490 ophthalmic product Drugs 0.000 claims 1
- CMVHOLZLFLESKY-UHFFFAOYSA-N Anisodine Natural products CN1C2CC(CC1C3OC23)C(=O)OC(O)(CO)c4ccccc4 CMVHOLZLFLESKY-UHFFFAOYSA-N 0.000 abstract description 28
- JEJREKXHLFEVHN-QDXGGTILSA-N anisodine Chemical compound C1([C@](O)(CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 JEJREKXHLFEVHN-QDXGGTILSA-N 0.000 abstract description 28
- 150000001875 compounds Chemical class 0.000 abstract description 15
- 230000000694 effects Effects 0.000 abstract description 9
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 abstract description 5
- 241000723346 Cinnamomum camphora Species 0.000 abstract description 5
- 229960000846 camphor Drugs 0.000 abstract description 4
- 229930008380 camphor Natural products 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- DSSYKIVIOFKYAU-XVKPBYJWSA-N (1s,4r)-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound C1C[C@@]2(C)C(=O)C[C@H]1C2(C)C DSSYKIVIOFKYAU-XVKPBYJWSA-N 0.000 abstract description 2
- 241000196324 Embryophyta Species 0.000 abstract description 2
- 150000003839 salts Chemical class 0.000 abstract description 2
- 230000004379 myopia Effects 0.000 description 19
- 208000001491 myopia Diseases 0.000 description 19
- 238000003756 stirring Methods 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 14
- 238000012360 testing method Methods 0.000 description 12
- 238000011587 new zealand white rabbit Methods 0.000 description 10
- 230000008859 change Effects 0.000 description 9
- 210000000744 eyelid Anatomy 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000005303 weighing Methods 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 238000011835 investigation Methods 0.000 description 7
- 238000002156 mixing Methods 0.000 description 6
- 230000000857 drug effect Effects 0.000 description 5
- 229930003347 Atropine Natural products 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 4
- 229960000396 atropine Drugs 0.000 description 4
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 3
- 208000007101 Muscle Cramp Diseases 0.000 description 3
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 3
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 210000001747 pupil Anatomy 0.000 description 3
- 239000008227 sterile water for injection Substances 0.000 description 3
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 3
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 2
- 208000006550 Mydriasis Diseases 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 229920002385 Sodium hyaluronate Polymers 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000001078 anti-cholinergic effect Effects 0.000 description 2
- 229960002233 benzalkonium bromide Drugs 0.000 description 2
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 description 2
- 229910021538 borax Inorganic materials 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- DGLRDKLJZLEJCY-UHFFFAOYSA-L disodium hydrogenphosphate dodecahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].OP([O-])([O-])=O DGLRDKLJZLEJCY-UHFFFAOYSA-L 0.000 description 2
- 230000004438 eyesight Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 239000012982 microporous membrane Substances 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 2
- 229940010747 sodium hyaluronate Drugs 0.000 description 2
- 239000004328 sodium tetraborate Substances 0.000 description 2
- 235000010339 sodium tetraborate Nutrition 0.000 description 2
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- PUETUDUXMCLALY-HOTGVXAUSA-N (-)-secoisolariciresinol Chemical compound C1=C(O)C(OC)=CC(C[C@@H](CO)[C@H](CO)CC=2C=C(OC)C(O)=CC=2)=C1 PUETUDUXMCLALY-HOTGVXAUSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- OGFXBIXJCWAUCH-UHFFFAOYSA-N meso-secoisolariciresinol Natural products C1=2C=C(O)C(OC)=CC=2CC(CO)C(CO)C1C1=CC=C(O)C(OC)=C1 OGFXBIXJCWAUCH-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 235000004239 secoisolariciresinol Nutrition 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000003442 weekly effect 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a pharmaceutical composition for treating pseudomyopia and application thereof, and belongs to the field of medicines. The invention provides application of combination of anisodine and vatupine in preparing medicaments for treating pseudomyopia, and also provides a pharmaceutical composition for treating pseudomyopia. The camphor Liu Jianhou martrope compound eye drops provided by the invention have the advantages that the active ingredients of the camphor powder and the martrope hydrobromide are extracted from plants and then crystallized into salt, so that the prepared compound eye drops have good curative effect, low side effect and stable quality, and a better choice is provided for the market.
Description
Technical Field
The invention relates to a pharmaceutical composition for treating pseudomyopia and application thereof, belonging to the field of medicines.
Background
Myopia is generally classified into pseudomyopia and true myopia, and mixed myopia. Pseudomyopia is the continuous contraction and cramping of the ciliary muscle due to excessive ocular use, increased lens thickness, and blurred vision. The muscle can be relaxed by using medicines, acupuncture, ear-buried needles and physiotherapy instruments or strengthening eye muscle exercise of the patient, so that fatigue is relieved, and the vision is recovered to a normal state. If the pseudomyopia is not relieved in time, the pseudomyopia can finally cause the enlargement of the ocular axis to become true myopia.
The eye drops such as atropine sulfate on the market at present are easy to rebound and have large side effects and the like for treating pseudomyopia, and the research on other medicaments for treating pseudomyopia is a clinical urgent problem to be solved.
There are reports that the compound anisodine injection is used for treating teenager pseudomyopia (Xiao, etc., clinical research of treating teenager pseudomyopia by the compound anisodine injection, chinese health care nutrition (late journal of ten days), 2014), the document discloses that the compound anisodine prepared by combining anisodine hydrobromide and procaine is used for treating pseudomyopia, wherein the anisodine has the anticholinergic effects of relieving smooth muscle spasm, expanding pupil, inhibiting salivary gland secretion, etc., and can regulate whole eye vascular function and improve blood supply of eyes. The central action, peripheral anticholinergic action such as smooth muscle spasm relieving, saliva secretion inhibiting and pupil dilating effects are slightly weaker than those of atropine, but the toxicity is much lower than those of atropine.
In addition, there are reports that the latter horse tropine used for ophthalmic examination optometry and mydriasis is used for treating pseudomyopia, and the effect and toxicity of the latter horse tropine are similar to those of atropine, but weaker. The mydriasis effect is faster than atropine, but the maintenance time is short, the effect is achieved 5-20 min after eye drop, the maximum is 30-90 min, and the duration is 18-48 min. The pupil is restored to normal within 12-36 h. Patent application number: 201610351530.X, name: an eye drop capable of preventing myopia discloses an eye drop capable of preventing myopia, which comprises a rear horse riding product, a preservative, a pH regulator, an isotonic regulator and a diluent, wherein the components are as follows: rear horse riding product: 0.01% -0.3%; preservative: 0.001% -0.05%; pH regulator: regulating pH to 6.6-7.2; 1% -10% of an isotonic regulator; dilution liquid: the balance. The eye drop can relieve muscle spasm in a short period and eliminate pseudomyopia state by injecting eyes daily or weekly before sleeping late when the eyes of a user are tired or have myopia tendency through the low-concentration back martrope, so that the purpose of preventing myopia is achieved.
At present, no report on the combined use of the anisodine and the post-martrop exists.
Disclosure of Invention
The technical scheme of the invention provides the application of the combination of the anisodine and the vatupine in preparing the medicine for treating pseudomyopia. The invention also provides a pharmaceutical composition for treating pseudomyopia.
The invention provides application of combination of anisodine and vatupine in preparing an ophthalmic medicament for treating pseudomyopia.
Wherein the weight ratio of the anisodine to the rear martolopine is as follows: 0.5-2:0.5-2.
Further preferably, the weight ratio of the anisodine to the rear martolidine is as follows: 1:2.
Wherein the anisodine is anisodine hydrobromide, and the post-martrop is post-martrop hydrobromide.
The preparation of the medicine is eye drops, eye ointment and eye gel.
The invention also provides a pharmaceutical composition for treating pseudomyopia, which is a preparation prepared from the active ingredients of the anisodine and the after-martrop, wherein the weight ratio of the anisodine to the after-martrop is as follows: 0.5-2:0.5-2.
Further preferably, the weight ratio of the anisodine to the rear martolidine is as follows: 1:2.
Wherein the preparation is eye drops, eye ointment and eye gel, and the preferred preparation is eye drops, wherein the mass percentage of the anisodine is 0.05-0.2%, and the mass percentage of the damascene is as follows: 0.05 to 0.2 percent.
Further preferably, the preparation is an eye drop, wherein the mass percentage of the anisodine is 0.05%, and the mass percentage of the damascene is as follows: 0.1%. The dosage of each application is as follows: 25 mug of anisodine and 50 mug of post-martrop.
Wherein the anisodine is anisodine hydrobromide, and the post-martrop is post-martrop hydrobromide.
The camphor Liu Jianhou martrope compound eye drops provided by the invention have the advantages that the active ingredients of the camphor powder and the martrope hydrobromide are extracted from plants and then crystallized into salt, so that the prepared compound eye drops have good curative effect, low side effect and stable quality, and a better choice is provided for the market.
Drawings
Figure 1 shows the sphere power change rate within 4 weeks of anisodine hydrobromide alone.
Fig. 2 shows the spherical diopter change rate of martrope over 4 weeks after hydrobromic acid alone.
Figure 3 shows the rate of change of spherical diopters within 4 weeks of the inventive combination of anisodine hydrobromide and post-hydrobromide martrope.
Detailed Description
EXAMPLE 1 preparation method of the eye drops of the invention
Mixing 100ml of sterile injectable water with 0.25g of borax and 2.4g of boric acid, dissolving, weighing 0.05g of anisodine and 0.1g of post-ma tuo pin, stirring, mixing, stirring, weighing 0.1g of sodium hyaluronate, and adding EDTA 2 Continuously stirring Na 0.05g and methyl benzoate 0.05g uniformly, adding water to fix volume, filtering with microporous membrane of 0.22 μm, and packaging to obtain eye drop.
EXAMPLE 2 preparation method of eye drops of the present invention
Taking 100ml of sterile water for injection, adding 0.5g of borax and 3.2g of boric acid, mixing and dissolving, then adding 1.2g of hydroxypropyl methylcellulose, stirring and dissolving, weighing 0.1g of anisodine and 0.1g of secoisolariciresinol, stirring and dissolving, uniformly mixing and stirring, weighing 0.15g of sodium hyaluronate, uniformly stirring, and finally adding EDTA 2 Continuously stirring Na 0.1g uniformly, adding water to a certain volume, filtering with a microporous filter membrane of 0.22 μm, and filling to obtain the eye drop.
EXAMPLE 3 preparation of the eye drops of the invention
Taking 100ml of sterile water for injection, adding 1.6g of sodium dihydrogen phosphate dihydrate and 0.4g of disodium hydrogen phosphate dodecahydrate for dissolution, weighing 0.05g of anisodine and 0.1g of post-martrope for stirring and dissolution, weighing 0.5g of povidone K, stirring uniformly after mixing and stirring uniformly, and finally adding EDTA 2 Continuously and uniformly stirring 0.05g of Na and 0.03g of benzalkonium bromide, adding water to fix the volumeFiltering with microporous membrane of 0.22 μm, and packaging.
EXAMPLE 4 preparation of the eye drops of the invention
Taking 100ml of sterile water for injection, adding 2.0g of sodium dihydrogen phosphate dihydrate and 1.0g of disodium hydrogen phosphate dodecahydrate for dissolution, weighing 0.1g of anisodine and 0.1g of post-martrope for stirring and dissolution, weighing 0.5g of povidone K, stirring uniformly after mixing and stirring uniformly, and finally adding EDTA 2 Continuously stirring 0.1g of Na and 0.03g of benzalkonium bromide uniformly, adding water to fix the volume, filtering by a microporous filter membrane with the diameter of 0.22 mu m, and filling to obtain the finished product.
EXAMPLE 5 investigation of the stability of the eye drops of the invention
The compound eye drops prepared in example 1 were subjected to stability investigation, and the results are shown in table 1:
TABLE 1 stability investigation results of compound eye drops of martrope after anisodine
Conclusion: the investigation result of the influencing factors shows that the main indexes such as the properties, related substances, isomers, content and the like of the two batches of samples have no obvious difference under the illumination condition; the product is stable in illumination conditions; the isomer and related substances of the sample all show obvious change at the high temperature of 60 ℃, and the isomer and related substances increase along with the increase of the standing time, and the other indexes have no obvious change; the temperature-sensitive product is sensitive to temperature, and the influence of temperature is noted in the storage and transportation processes of the product.
The long-term test and investigation result shows that: the stability results of the embodiments are basically consistent, and the main indexes are as follows: the properties, colors, isomers, related substances, content and the like are not changed obviously; the sterility test was satisfactory during the investigation. The product has stable storage condition at normal temperature.
Stability: product influence factor experiments and long term conditions (25 ℃, RH65±5%) after 3 months of investigation: under the condition of illumination (5000 LuX), the prepared eye drop sample has no obvious difference between each detection item of the sample and 0 day, which proves that the product has better light stability, and has no obvious change in pH and content compared with the detection result of 0 day under the condition of high temperature 60 ℃, and no detected isomer and increased tropinic acid impurity, so the product needs to control the temperature of the transportation and storage environment. Under the condition of long-term test for 3 months, the detection items of the sample have no obvious difference from the comparison of 0 month, which indicates that the product is stable under the normal-temperature storage condition.
The following demonstrates the beneficial effects of the invention by pharmacodynamic tests.
Test example 1 screening of best Compound formulation of Cinnamomum camphora Liu Jianhou and horse tropine
A shape deprivation myopia model is established through eyelid suture operation of New Zealand white rabbits, and the drug effect of anisodine, after-martrop and compound composition thereof on the New Zealand white rabbits myopia model is tested, and the result shows that compared with a single preparation of the camphor Liu Jianhou martrop compound eye drops, the spherical diopter value of a model animal after administration of the anisodine hydrobromide eye drops and the after-martrop hydrobromide eye drops has an obviously rising trend compared with that of the model animal before administration, and the myopia degree of the model animal is obviously improved.
1. Experimental procedure
Before the start of the experiment: the animal adaptation period was carried out as required and the experimental animals were operated as shown in the following table during the adaptation period. Animals included in the experiment will be selected after the end of the conditioning period based on the animal's health status and data during the conditioning period.
And (3) model making: the eye drop administration of levofloxacin eye drops is started for preventing infection 2 days before operation, on the same day, 0.06-0.09 mL/kg standard ear margin is used for intravenous injection of sultai-domaticin mixed solution (each milliliter of mixed solution comprises 0.5 mg domaticin and 50 mg sultai), a new zealand white rabbit after anesthesia is placed on a console on one side, two eyes are given with 0.25 g/L gentamicin physiological saline mixed solution for flushing conjunctival sac for disinfection, left hand forceps slightly lift an upper eyelid, right hand ophthalmic scissors are used for cutting an outer canthus part from an inner canthus part to an eyelid part from 2-3 mm, the lower eyelid is used for the same operation, then the upper eyelid is sewed by a 4-0 suture line, and the eye drops are used for three continuous days after operation. Eyelid sutures were checked once a day after surgical suturing, and once the suture was found to fall off, the suture was immediately re-sutured.
Sphere diopter measurement: animals were transferred from the indoor lighting environment to the ophthalmic laboratory and the mean was taken 6 times using infrared mode measurement of the refractometer. Spherical diopters were measured at different time points: baseline, pre-eyedrop, post-eyedrop Day1, day2, day3, week1, week2, week3, week4.
The study is a drug effect experiment of the test object on a New Zealand white rabbit myopia model. Using 63 animals of New Zealand white rabbits (less than 2 weeks old), forming a vision deprivation myopia model by applying a eyelid sewing method, collecting spherical diopter data by using a full-computer automatic optometry device HandyRey-K after molding for 8 weeks, and screening 48 animals with average spherical diopter value of less than 2.75D of eyes according to the spherical diopter result, randomly dividing into 8 groups, wherein 6 animals are selected in each group; the eyes of the animals in the group are dripped into eyes for administration once a day for four weeks; spherical diopter measurements were performed at Day1, day2, day3, week1, week2, week3, week4, respectively, after the first dose.
2. Experimental results
2.1 experiments on different proportions of anisodine and rear Matropine
The results of measuring spherical diopters 4 weeks after administration are shown in Table 2:
TABLE 2 optimal formulation screening of anisodine and post-ambroxol
Test conclusion after screening proportioning: the experiment induces a New Zealand white rabbit myopia model through eyelid suture operation, tests the drug effect of a test object on the New Zealand white rabbit myopia model, and measures spherical diopter values at different time points within 4 weeks after the test object is continuously dropped into eyes, and the result shows that the myopia degree of a model animal can be improved after the combined administration of the martrope hydrobromide and the anisodine hydrobromide; the optimal proportion is 0.05% of camphor Liu Jianjia 0.1.1% of hydrobromic acid and then 0.1% of hydrobromic acid, at the moment, the spherical diopter of New Zealand white rabbits is maximally 4.5, and the diopter change rate is maximally 260%.
2.2 The compound preparation and the single preparation of the invention have spherical diopter change rate before and after administration
The experimental results show that: for 4 weeks of continuous dosing, the difference in spherical diopter values of the 0.05% anisodine hydrobromide group, the 0.05% post-martrope hydrobromide group, the 0.05% anisodine hydrobromide-0.05% post martrope group was of great significance (p < 0.01) compared to the saline group control; the spherical diopter change rate of the white rabbit after the compound administration of the anisodine hydrobromide and the martrop hydrobromide is far greater than that of a single preparation of the anisodine hydrobromide and the martrop hydrobromide, which shows that the combination of the two can obviously improve the drug effect, and better curative effect is observed in the treatment process (see figures 1, 2 and 3).
In summary, the eye drop induces a New Zealand white rabbit myopia model through eyelid suture operation, the drug effect of a test object on the New Zealand white rabbit myopia model is tested, the test object continuously drops eyes for 4 weeks at different time points to measure spherical diopter values, and the result shows that after the compound eye drop of the rear martrope with the content of 0.05% of anisodine and 0.1% by mass is administrated, the spherical diopter values of the model animal obviously have an ascending trend compared with the model animal myopia degree before administration.
Claims (4)
1. Use of anisodine hydrobromide in combination with post-ambroxol in the manufacture of an ophthalmic medicament for the treatment of pseudomyopia; the weight ratio of the anisodine hydrobromide to the post-mitopine hydrobromide is as follows: 1:2.
2. Use according to claim 1, characterized in that: the preparation of the ophthalmic medicine is eye drops, eye ointment and ophthalmic gel.
3. A pharmaceutical composition for treating pseudomyopia, characterized in that: the preparation is prepared from anisodine hydrobromide and after-hydrobromic-acid martrop serving as active ingredients, wherein the weight ratio of the anisodine hydrobromide to the after-hydrobromic-acid martrop is as follows: 1:2.
4. A pharmaceutical composition according to claim 3, characterized in that: the preparation is eye drops, wherein the concentration of the anisodine hydrobromide is 0.05 percent, and the concentration of the post-hydrobromic-acid martrop is 0.1 percent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410096928.8A CN117599054B (en) | 2024-01-24 | 2024-01-24 | Pharmaceutical composition for treating pseudomyopia and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410096928.8A CN117599054B (en) | 2024-01-24 | 2024-01-24 | Pharmaceutical composition for treating pseudomyopia and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN117599054A CN117599054A (en) | 2024-02-27 |
| CN117599054B true CN117599054B (en) | 2024-03-29 |
Family
ID=89956541
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410096928.8A Active CN117599054B (en) | 2024-01-24 | 2024-01-24 | Pharmaceutical composition for treating pseudomyopia and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117599054B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1222392A (en) * | 1997-11-18 | 1999-07-14 | 宋琛 | Compound injection for curing ischemic eye disease |
| CN1660095A (en) * | 2004-12-16 | 2005-08-31 | 北京紫竹药业有限公司 | Oral liquid of compound anisodine, preparation method and usage |
| CN101219143A (en) * | 2008-01-25 | 2008-07-16 | 北京紫竹药业有限公司 | Use of anisodine in preparing medicament for treating amblyopia |
| CN113968853A (en) * | 2020-07-22 | 2022-01-25 | 中国农业大学 | Hapten and artificial antigen of atropine alkaloid, and preparation method and application thereof |
| CN114414679A (en) * | 2021-12-27 | 2022-04-29 | 吉林省农业科学院 | Method for detecting belladonna alkaloid in animal tissue |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2598436A1 (en) * | 2005-02-22 | 2006-08-31 | Ceres, Inc. | Modulating plant alkaloids |
| WO2007117693A2 (en) * | 2006-04-07 | 2007-10-18 | Ceres, Inc. | Regulatory protein-regulatory region associations related to alkaloid biosynthesis |
| JP6133790B2 (en) * | 2011-02-18 | 2017-05-24 | ザ スクリプス リサーチ インスティテュート | Directed differentiation of oligodendrocyte progenitor cells to myelinating cell fate |
-
2024
- 2024-01-24 CN CN202410096928.8A patent/CN117599054B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1222392A (en) * | 1997-11-18 | 1999-07-14 | 宋琛 | Compound injection for curing ischemic eye disease |
| CN1660095A (en) * | 2004-12-16 | 2005-08-31 | 北京紫竹药业有限公司 | Oral liquid of compound anisodine, preparation method and usage |
| CN101219143A (en) * | 2008-01-25 | 2008-07-16 | 北京紫竹药业有限公司 | Use of anisodine in preparing medicament for treating amblyopia |
| CN113968853A (en) * | 2020-07-22 | 2022-01-25 | 中国农业大学 | Hapten and artificial antigen of atropine alkaloid, and preparation method and application thereof |
| CN114414679A (en) * | 2021-12-27 | 2022-04-29 | 吉林省农业科学院 | Method for detecting belladonna alkaloid in animal tissue |
Non-Patent Citations (3)
| Title |
|---|
| "The pharmacological properties of anisodamine";Jay M Poupko，et al;《J Appl Toxicol . 》;20070331;第27卷(第2期);第342-343页。 * |
| 托品生物碱合成研究概况;杨靖华;;中国医药工业杂志(第05期);第35-39页。 * |
| 治疗青少年假性近视药物新剂型-治近定眼膏研究的探讨;曾育麟;;云南中医学院学报(第01期);第32-34页。 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN117599054A (en) | 2024-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Tigges et al. | Effects of muscarinic cholinergic receptor antagonists on postnatal eye growth of rhesus monkeys | |
| McBrien et al. | Atropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism. | |
| US6410544B1 (en) | Cholinergic agents in the treatment of presbyopia | |
| CN102170865A (en) | Eye drop with difluprednate for macular edema treatment | |
| CN101554369B (en) | External spraying agent and eye drop of compound oil nano-emulsion as well as preparation method thereof | |
| KR102427225B1 (en) | Pharmaceutical composition comprising sglt-2 inhibitor for preventing or treating diabetic opthalmopathy disease | |
| WO2020219707A1 (en) | Compositions and methods for treatment of ocular conditions | |
| de Oliveira Dias et al. | Intravitreal injection of ziv-aflibercept in patient with refractory age-related macular degeneration | |
| CN104688672B (en) | Puerarin gel eyedrop is preparing the application in treating retinopathy medicine | |
| CN115105512A (en) | Application of dehydroepiandrosterone in preparing medicine for preventing and treating eye myopia, its dosage form and preparation method | |
| WO2021021646A1 (en) | Compositions and methods for treatment of presbyopia | |
| CN102038953B (en) | Composite for local anesthesia before ophthalmologic operation and preparation method and application thereof | |
| Ostrin et al. | Effects of pirenzepine on pupil size and accommodation in rhesus monkeys | |
| Jampol | Oxygen therapy and intraocular oxygenation. | |
| KR20230083315A (en) | Use of phenehclidine in the treatment or prevention of vision-impairing eye diseases | |
| CN117599054B (en) | Pharmaceutical composition for treating pseudomyopia and application thereof | |
| Kent et al. | Vitreous concentration of topically applied brimonidine-purite 0.15% | |
| POLLACK et al. | Dose-Response Effects of Tropicamide HCI | |
| CN103720524A (en) | Method for making primate dry age-related macular degeneration disease model | |
| CN110833526A (en) | Eye preparation for preventing and treating juvenile myopia and preparation method thereof | |
| CN112891326B (en) | Natamycin-loaded alginic acid gel medicine film and preparation method thereof | |
| CRAIG BROWN et al. | Use of dilute drug solutions for routine cycloplegia and mydriasis | |
| Crawford et al. | Effects of various anesthetic and autonomic drugs on refraction in monkeys | |
| Davidson et al. | Effect of topical ophthalmic latanoprost on intraocular pressure in normal horses | |
| CN102145162A (en) | Injection of medicine for treating premature delivery |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |