JP2022520779A - 注射可能なフェノール製剤およびその使用の方法 - Google Patents
注射可能なフェノール製剤およびその使用の方法 Download PDFInfo
- Publication number
- JP2022520779A JP2022520779A JP2021546842A JP2021546842A JP2022520779A JP 2022520779 A JP2022520779 A JP 2022520779A JP 2021546842 A JP2021546842 A JP 2021546842A JP 2021546842 A JP2021546842 A JP 2021546842A JP 2022520779 A JP2022520779 A JP 2022520779A
- Authority
- JP
- Japan
- Prior art keywords
- phenol
- cyclodextrin
- phenolic
- weight
- preparation
- 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.)
- Granted
Links
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 title claims abstract description 245
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims description 20
- 239000000203 mixture Substances 0.000 claims abstract description 88
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 51
- 238000009472 formulation Methods 0.000 claims abstract description 45
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 44
- 210000005036 nerve Anatomy 0.000 claims abstract description 32
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 11
- 229940127557 pharmaceutical product Drugs 0.000 claims abstract description 10
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 6
- 238000002347 injection Methods 0.000 claims description 35
- 239000007924 injection Substances 0.000 claims description 35
- 239000002904 solvent Substances 0.000 claims description 13
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 239000002537 cosmetic Substances 0.000 claims description 7
- 230000000699 topical effect Effects 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 3
- 210000004204 blood vessel Anatomy 0.000 claims description 3
- 230000002934 lysing effect Effects 0.000 claims description 2
- 230000008467 tissue growth Effects 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 26
- 210000001519 tissue Anatomy 0.000 abstract description 21
- 241001465754 Metazoa Species 0.000 abstract description 14
- 210000003205 muscle Anatomy 0.000 abstract description 7
- 210000004872 soft tissue Anatomy 0.000 abstract description 4
- 230000002411 adverse Effects 0.000 abstract description 3
- 238000010586 diagram Methods 0.000 abstract description 2
- 230000007659 motor function Effects 0.000 abstract description 2
- 230000002828 effect on organs or tissue Effects 0.000 abstract 1
- 239000008393 encapsulating agent Substances 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 17
- 230000036407 pain Effects 0.000 description 16
- 208000002193 Pain Diseases 0.000 description 15
- 230000009918 complex formation Effects 0.000 description 13
- 210000002027 skeletal muscle Anatomy 0.000 description 12
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (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-carboxylic acid Chemical compound 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 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 11
- 229920002674 hyaluronan Polymers 0.000 description 11
- 229960003160 hyaluronic acid Drugs 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 229940097362 cyclodextrins Drugs 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 210000003497 sciatic nerve Anatomy 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 208000008238 Muscle Spasticity Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 206010028320 muscle necrosis Diseases 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 208000005392 Spasm Diseases 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000005538 encapsulation Methods 0.000 description 6
- 208000004296 neuralgia Diseases 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical group C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000001879 gelation Methods 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 210000003141 lower extremity Anatomy 0.000 description 5
- 229920000609 methyl cellulose Polymers 0.000 description 5
- 239000001923 methylcellulose Substances 0.000 description 5
- 229920001983 poloxamer Polymers 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 206010056677 Nerve degeneration Diseases 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000017074 necrotic cell death Effects 0.000 description 4
- 208000018198 spasticity Diseases 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000006820 Arthralgia Diseases 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- 206010033799 Paralysis Diseases 0.000 description 3
- 208000007542 Paresis Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000536 complexating effect Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 210000001087 myotubule Anatomy 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 229960000502 poloxamer Drugs 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000002271 resection Methods 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000001248 thermal gelation Methods 0.000 description 3
- 230000000451 tissue damage Effects 0.000 description 3
- 231100000827 tissue damage Toxicity 0.000 description 3
- 230000037303 wrinkles Effects 0.000 description 3
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 206010058019 Cancer Pain Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000008454 Hyperhidrosis Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000028752 abnormal posture Diseases 0.000 description 2
- 231100000360 alopecia Toxicity 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229920006184 cellulose methylcellulose Polymers 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- -1 granulators Substances 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000013150 knee replacement Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002690 local anesthesia Methods 0.000 description 2
- 230000008338 local blood flow Effects 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000037023 motor activity Effects 0.000 description 2
- 230000007830 nerve conduction Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- 239000004848 polyfunctional curative Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000001148 spastic effect Effects 0.000 description 2
- 210000004243 sweat Anatomy 0.000 description 2
- 210000001179 synovial fluid Anatomy 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- NZAQRZWBQUIBSF-UHFFFAOYSA-N 4-(4-sulfobutoxy)butane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCCOCCCCS(O)(=O)=O NZAQRZWBQUIBSF-UHFFFAOYSA-N 0.000 description 1
- BMFMQGXDDJALKQ-BYPYZUCNSA-N Argininic acid Chemical compound NC(N)=NCCC[C@H](O)C(O)=O BMFMQGXDDJALKQ-BYPYZUCNSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 208000002506 Darier Disease Diseases 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 208000009774 Follicular Cyst Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 206010018735 Groin pain Diseases 0.000 description 1
- 208000004095 Hemifacial Spasm Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 206010060800 Hot flush Diseases 0.000 description 1
- 206010070511 Hypoxic-ischaemic encephalopathy Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010023369 Keratosis follicular Diseases 0.000 description 1
- 208000003947 Knee Osteoarthritis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 208000001244 Linear IgA Bullous Dermatosis Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000002472 Morton Neuroma Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
- 208000005890 Neuroma Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000000114 Pain Threshold Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000036496 Pelvic floor dyssynergia Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000004350 Strabismus Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 206010062174 Venous aneurysm Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- WQZGKKKJIJFFOK-UHFFFAOYSA-N alpha-D-glucopyranose Natural products OCC1OC(O)C(O)C(O)C1O WQZGKKKJIJFFOK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 201000002898 anismus Diseases 0.000 description 1
- 125000005427 anthranyl group Chemical group 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 208000009973 brain hypoxia - ischemia Diseases 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000007012 clinical effect Effects 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000000871 endothelium corneal Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 238000002676 facial rejuvenation Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000002637 fluid replacement therapy Methods 0.000 description 1
- 238000002594 fluoroscopy Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 235000021472 generally recognized as safe Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 208000002557 hidradenitis Diseases 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 238000011540 hip replacement Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000037315 hyperhidrosis Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 201000004607 keratosis follicularis Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 208000029631 linear IgA Dermatosis Diseases 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 201000003265 lymphadenitis Diseases 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000037040 pain threshold Effects 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 229940044476 poloxamer 407 Drugs 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 201000010727 rectal prolapse Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000001057 smooth muscle myoblast Anatomy 0.000 description 1
- 208000010485 smooth muscle tumor Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 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 1
- 239000007787 solid Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 210000003901 trigeminal nerve Anatomy 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 229940006076 viscoelastic substance Drugs 0.000 description 1
- 239000003190 viscoelastic substance Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000007794 visualization technique Methods 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000002517 zygapophyseal joint Anatomy 0.000 description 1
Images
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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/738—Cyclodextrins
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
- C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/26—Cellulose ethers
- C08L1/28—Alkyl ethers
- C08L1/286—Alkyl ethers substituted with acid radicals, e.g. carboxymethyl cellulose [CMC]
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/16—Cyclodextrin; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Anesthesiology (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Birds (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Emergency Medicine (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Biomedical Technology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
Abstract
Description
[実施例1A]インサイチュのゲル化
[実施例1B]粘弾性製剤
[実施例2]フェノールおよび様々なシクロデキストリンを使用する投与試験
[実施例3]フェノールおよびシクロデキストリンを使用するさらなる試験
1. Brewster ME and Loftsson T (2007) Cyclodextrins as pharmaceutical solubilizers. Advanced Drug 143, Delivery Reviews 59: 645-666.
2. Lin, S-Fen and Kenneth, C. A (1983) Complex Formation Between α-Cyclodextrin and 4-Substituted Phenols Studied by Potentiometric and Competitive Spectrophotometric Methods. Journal of Pharmaceutical Sciences. 72 (11), 1333-1338.
3. Yin, Q., Li, J., Zheng, Q., Yang, X., Rong Lv1, Ma,L., Liu,J., Zhu, T and Zhang, W. The quaternary lidocaine derivative QX-314 in combination with bupivacaine for long-lasting nerve block: Efficacy, toxicity, and the optimal formulation in rats. PLoS One. 2017; 12(3): e0174421.
4. Wang, Z., Huang, H., Yang, S., Huang, S., Guo, J., Tang, Q. and Qi, F. Long-term effect of ropivacaine nanoparticles for sciatic nerve block on postoperative pain in rats. Int. J. Nanomed. 2016:11 2081-2090.
5. Loyd DR, Chen PB, Hargreaves KM. Anti-hyperalgesic effects of anti-serotonergic compounds on serotonin- and capsaicin-evoked thermal hyperalgesia in the rat. Neuroscience. 2012 Feb 17;203:207-15. doi: 10.1016/j.neuroscience.2011.12.019. Epub 2011 Dec 20.
6. Liu XJ, White TD, Sawynok J. Intraplantar injection of glutamate evokes peripheral adenosine release in the rat hind paw: involvement of peripheral ionotropic glutamate receptors and capsaicin-sensitive sensory afferents. J Neurochem. 2002 Feb;80(4):562-70.
7. Lin CC, et al. Optimal effect of Phenol in Sciatic Nerve. Chinese Journal of Physiology 2015; 58 (4): 237-243.
8. Szente, Lajos, Szejtli J and Kis, G.L. Spontaneous Opalescence of Aqueous γ- Cyclodextrin Solutions: Complex Formation or Self-Aggregation? Journal of Pharmaceutical Sciences 1998: 87(6): 778-781.
Claims (15)
- フェノールと、
前記フェノールの少なくとも一部と複合体形成するシクロデキストリンまたはその誘導体と、
少なくとも1つの薬理学的に許容される溶媒と、を含むフェノール製剤。 - 注射のためのものである、請求項1に記載のフェノール製剤。
- 前記シクロデキストリンがヒドロキシプロピル-β-シクロデキストリン(HP-β-CD)である、請求項2に記載のフェノール製剤。
- 前記ヒドロキシプロピル-β-シクロデキストリンの濃度が、前記製剤の約10重量%~約20重量%(w/w)である、請求項3に記載のフェノール製剤。
- 前記ヒドロキシプロピル-β-シクロデキストリンの濃度が、前記製剤の約12重量%~約18重量%(w/w)である、請求項4に記載のフェノール製剤。
- 前記フェノールの濃度が、前記製剤の約3重量%~約9重量%(w/w)である、請求項5に記載のフェノール製剤。
- 前記フェノールの濃度が、前記製剤の約6重量%(w/w)である、請求項6に記載のフェノール製剤。
- 前記シクロデキストリンがヒドロキシプロピル-β-シクロデキストリンである、請求項1に記載のフェノール製剤。
- 哺乳動物において神経ブロックを生成するための方法であって、
有効量のフェノール製剤を投与するステップを含み、前記製剤が:
フェノールと、
前記フェノールの少なくとも一部と複合体形成するシクロデキストリンまたはその誘導体と、
投与のための少なくとも1つの薬理学的に許容される溶媒と、を含む方法。 - 前記投与するステップが注射によるものである、請求項9に記載の方法。
- 前記投与するステップが局所適用によるものである、請求項9に記載の方法。
- それを必要とする患者における、治療目的の、化粧目的のまたは組織溶解目的の状態を処置するための方法であって、
有効量のフェノール製剤を患者の神経、血管、腫瘍または組織成長に近接しているかまたはその中の、生理学的標的領域中に注射またはそれに近接して適用するステップを含み、前記製剤が、
フェノールと、
前記フェノールの少なくとも一部と複合体形成するシクロデキストリンまたはその誘導体と、
注射のための少なくとも1つの薬理学的に許容される溶媒と、を含む方法。 - 前記フェノール製剤が、約4重量%~約9重量%のフェノール、および約10重量%~約20重量%のシクロデキストリンまたは誘導体を含む、請求項12に記載の方法。
- 注射のためのフェノール組成物を作製する方法であって、
シクロデキストリンまたはその誘導体と注射のための薬理学的に許容される溶媒とを合わせ、
前記シクロデキストリンまたはその誘導体と前記注射のための薬理学的に許容される溶媒とを前記シクロデキストリンが溶解するまで混合し、
フェノールを添加し、前記フェノールが前記組成物中に溶解するまで前記組成物を混合する、工程を含む方法。 - 局所適用のためのものである、請求項1に記載のフェノール製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962806188P | 2019-02-15 | 2019-02-15 | |
US62/806,188 | 2019-02-15 | ||
PCT/US2020/015690 WO2020167476A1 (en) | 2019-02-15 | 2020-01-29 | Injectable phenol formulations and methods of their use |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2022520779A true JP2022520779A (ja) | 2022-04-01 |
JPWO2020167476A5 JPWO2020167476A5 (ja) | 2022-11-08 |
JP7455852B2 JP7455852B2 (ja) | 2024-03-26 |
Family
ID=72042651
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021546842A Active JP7455852B2 (ja) | 2019-02-15 | 2020-01-29 | 注射可能なフェノール製剤およびその使用の方法 |
Country Status (6)
Country | Link |
---|---|
US (3) | US10959962B2 (ja) |
EP (1) | EP3923916A4 (ja) |
JP (1) | JP7455852B2 (ja) |
CA (1) | CA3129648A1 (ja) |
MX (1) | MX2021009777A (ja) |
WO (1) | WO2020167476A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112691091A (zh) * | 2021-01-09 | 2021-04-23 | 胡宝贤 | 低浓度石炭酸的新应用 |
US20230190660A1 (en) * | 2021-12-03 | 2023-06-22 | Path | Encapsulated pharmaceutical compositions, related methods of making, and related methods of treatment |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0625056B2 (ja) | 1989-06-01 | 1994-04-06 | 大幸薬品株式会社 | 鎮痙剤 |
CA2446060A1 (en) * | 2001-05-07 | 2002-11-14 | Corium International | Compositions and delivery systems for administration of a local anesthetic agent |
JP4150772B2 (ja) * | 2001-09-14 | 2008-09-17 | 独立行政法人産業技術総合研究所 | シクロデキストリンを含有するフェノール重合物 |
US7964644B2 (en) | 2002-07-19 | 2011-06-21 | Mestex Ag | Use of neurotoxic substances for the production of a means for the treatment of joint paint and method for application of said means |
KR100834232B1 (ko) * | 2004-01-30 | 2008-05-30 | 화이자 프로덕츠 인크. | 액체 투여형용 베타-시클로덱스트린을 사용하는 다수회투여 제형을 얻기 위한 항균 방부제 |
US20120190750A1 (en) * | 2011-01-24 | 2012-07-26 | Uni-Pharma Kleon Tsetis Pharmaceutical Laboratories S.A. | Stable ready to use injectable paracetamol formulation |
DK2785352T3 (da) * | 2011-11-29 | 2020-05-25 | Jurox Pty Ltd | Stabile injicerbare farmaceutiske sammensætninger omfattende 2-hydroxypropyl-beta-cyclodextrin og alfaxalon |
US9295512B2 (en) | 2013-03-15 | 2016-03-29 | Myoscience, Inc. | Methods and devices for pain management |
JP6238190B2 (ja) * | 2013-07-04 | 2017-11-29 | 公立大学法人大阪市立大学 | コラーゲン産生促進用、エラスチン産生促進用および/またはケラチノサイト遊走促進用組成物 |
WO2015013330A2 (en) | 2013-07-22 | 2015-01-29 | Kineta One, Llc | Ophthalmic uses of toxin-based therapeutic peptides and pharmaceutical compositions thereof |
CN103602325B (zh) * | 2013-11-18 | 2016-08-03 | 中国石油化工股份有限公司 | 一种延缓交联凝胶调剖剂及其制备方法 |
WO2016014750A1 (en) | 2014-07-23 | 2016-01-28 | Landy Toth | Precision chemical ablation and treatment of tissues |
AU2016214996B2 (en) * | 2015-02-06 | 2021-03-04 | Marinus Pharmaceuticals, Inc. | Intravenous ganaxolone formulations and their use in treating status epilepticus and other seizure disorders |
EP3288626A4 (en) | 2015-04-27 | 2019-01-23 | Reflex Medical Inc. | SYSTEMS AND METHODS FOR SYMPATHETIC CARDIO-PULMONARY NEUROMODULATION |
EP3442998A4 (en) * | 2016-04-12 | 2020-04-01 | Cell And Molecular Tissue Engineering, LLC | SYSTEMS, METHODS AND PRODUCTS TO MINIMIZE TISSUE REACTIONS AND TISSUE INJURY AT AN INFUSION SITE |
-
2020
- 2020-01-29 US US16/776,184 patent/US10959962B2/en active Active
- 2020-01-29 MX MX2021009777A patent/MX2021009777A/es unknown
- 2020-01-29 JP JP2021546842A patent/JP7455852B2/ja active Active
- 2020-01-29 CA CA3129648A patent/CA3129648A1/en active Pending
- 2020-01-29 WO PCT/US2020/015690 patent/WO2020167476A1/en unknown
- 2020-01-29 EP EP20756108.5A patent/EP3923916A4/en active Pending
-
2021
- 2021-01-28 US US17/160,951 patent/US11083694B2/en active Active
- 2021-01-28 US US17/160,993 patent/US11083695B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
MX2021009777A (es) | 2021-12-15 |
US10959962B2 (en) | 2021-03-30 |
US20200261377A1 (en) | 2020-08-20 |
EP3923916A1 (en) | 2021-12-22 |
JP7455852B2 (ja) | 2024-03-26 |
US11083695B2 (en) | 2021-08-10 |
EP3923916A4 (en) | 2022-12-21 |
US20210145767A1 (en) | 2021-05-20 |
US20210145766A1 (en) | 2021-05-20 |
CA3129648A1 (en) | 2020-08-20 |
US11083694B2 (en) | 2021-08-10 |
WO2020167476A1 (en) | 2020-08-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Bellotti et al. | Injectable thermoresponsive hydrogels as drug delivery system for the treatment of central nervous system disorders: A review | |
Soiberman et al. | Subconjunctival injectable dendrimer-dexamethasone gel for the treatment of corneal inflammation | |
JP7334994B2 (ja) | デンドリマー-生体接着性ポリマーヒドロゲルナノ接着剤およびその使用 | |
Madan et al. | In situ forming polymeric drug delivery systems | |
US20210338570A1 (en) | Radiation sensitizer or anti-cancer chemotherapy sensitizer | |
ES2382509T3 (es) | Composiciones de ketorolaco trometamol para el tratamiento o la prevención del dolor ocular | |
HU220864B1 (en) | Reversible, thermally gelling water-base medicinal compositions | |
JP2022520779A (ja) | 注射可能なフェノール製剤およびその使用の方法 | |
US11426418B2 (en) | Injectable long-acting semi-solid gel formulations | |
JP2023075278A (ja) | 薬剤送達用生体溶解性医薬ゲル | |
TWI538697B (zh) | 肝素之局部劑型 | |
Jug et al. | Cyclodextrin-based pharmaceuticals | |
AU2019208350B2 (en) | Suspension compositions of multi-target inhibitors | |
CN111655236B (zh) | 可注射长效局麻药半固体凝胶制剂 | |
CN113262302B (zh) | 可注射长效半固体凝胶制剂 | |
Murali et al. | Propranolol hydrochloride topical gel for the treatment of infantile hemangioma | |
JP2023544311A (ja) | テストステロンの延長送達のための生分解性ポリマー送達システム | |
TW201622734A (zh) | 含多醣之充填劑之活體降解 | |
CN117482216A (zh) | 治疗角膜内皮损伤的超声介导水凝胶制剂 | |
TW202038928A (zh) | 多目標抑製劑的懸浮液組合物 | |
BR102016015590A2 (pt) | Intravital implants of polygactic-coglicolic acid (plga) containing lupeol or derivatives applied to the treatment of eyelium diseases with angiogenic base as diabetic retinopathy |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20211110 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20211110 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221028 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20221028 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230920 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230922 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231218 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20240306 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240313 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7455852 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |