DE69312947T2 - Proteinhaftige arzneimittel mit verzögerter wirkstoffabgabe - Google Patents
Proteinhaftige arzneimittel mit verzögerter wirkstoffabgabeInfo
- Publication number
- DE69312947T2 DE69312947T2 DE69312947T DE69312947T DE69312947T2 DE 69312947 T2 DE69312947 T2 DE 69312947T2 DE 69312947 T DE69312947 T DE 69312947T DE 69312947 T DE69312947 T DE 69312947T DE 69312947 T2 DE69312947 T2 DE 69312947T2
- Authority
- DE
- Germany
- Prior art keywords
- biologically active
- peg
- preparation
- triacetin
- protein
- 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.)
- Expired - Fee Related
Links
- 239000003814 drug Substances 0.000 title description 6
- 239000013543 active substance Substances 0.000 title description 2
- 206010012186 Delayed delivery Diseases 0.000 title 1
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims abstract description 67
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 47
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 47
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 35
- 239000001087 glyceryl triacetate Substances 0.000 claims abstract description 34
- 235000013773 glyceryl triacetate Nutrition 0.000 claims abstract description 34
- 229960002622 triacetin Drugs 0.000 claims abstract description 34
- 239000000725 suspension Substances 0.000 claims abstract description 22
- 101710142969 Somatoliberin Proteins 0.000 claims abstract description 16
- 108010051696 Growth Hormone Proteins 0.000 claims abstract description 14
- 102000018997 Growth Hormone Human genes 0.000 claims abstract description 14
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims abstract description 12
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 11
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 claims abstract 4
- 238000002360 preparation method Methods 0.000 claims description 37
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 12
- 108010006025 bovine growth hormone Proteins 0.000 claims description 12
- 241000283690 Bos taurus Species 0.000 claims description 8
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 claims description 5
- 239000008267 milk Substances 0.000 claims description 5
- 235000013336 milk Nutrition 0.000 claims description 5
- 210000004080 milk Anatomy 0.000 claims description 5
- 101000825768 Bos taurus Somatoliberin Proteins 0.000 claims description 4
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 claims description 3
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 claims description 3
- 235000013365 dairy product Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 2
- 239000007927 intramuscular injection Substances 0.000 claims description 2
- 238000010254 subcutaneous injection Methods 0.000 claims description 2
- 239000007929 subcutaneous injection Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 20
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 13
- 230000002035 prolonged effect Effects 0.000 abstract description 10
- 238000013268 sustained release Methods 0.000 abstract description 8
- 239000012730 sustained-release form Substances 0.000 abstract description 8
- 230000000975 bioactive effect Effects 0.000 abstract 2
- 230000002459 sustained effect Effects 0.000 abstract 1
- 238000002347 injection Methods 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 238000009472 formulation Methods 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 18
- 102100022831 Somatoliberin Human genes 0.000 description 14
- 244000309465 heifer Species 0.000 description 14
- 239000003981 vehicle Substances 0.000 description 7
- 238000010241 blood sampling Methods 0.000 description 6
- 230000003111 delayed effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 238000001295 Levene's test Methods 0.000 description 2
- 240000004658 Medicago sativa Species 0.000 description 2
- 235000017587 Medicago sativa ssp. sativa Nutrition 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 230000002997 prostaglandinlike Effects 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000004460 silage Substances 0.000 description 2
- 229950000624 somavubove Drugs 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 101800000414 Corticotropin Proteins 0.000 description 1
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 101710128967 Somatotropin-1 Proteins 0.000 description 1
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 229960000258 corticotropin Drugs 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 239000003676 hair preparation Substances 0.000 description 1
- 239000007970 homogeneous dispersion Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- -1 poly(oxy-1,2-ethanediyl Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
Classifications
-
- 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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/25—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Reproductive Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94787292A | 1992-09-21 | 1992-09-21 | |
| US96336592A | 1992-10-20 | 1992-10-20 | |
| PCT/US1993/007756 WO1994006452A1 (en) | 1992-09-21 | 1993-08-23 | Sustained-release protein formulations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69312947D1 DE69312947D1 (de) | 1997-09-11 |
| DE69312947T2 true DE69312947T2 (de) | 1998-01-08 |
Family
ID=27130263
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69312947T Expired - Fee Related DE69312947T2 (de) | 1992-09-21 | 1993-08-23 | Proteinhaftige arzneimittel mit verzögerter wirkstoffabgabe |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6011011A (enExample) |
| EP (1) | EP0661989B1 (enExample) |
| JP (2) | JP3756512B2 (enExample) |
| AT (1) | ATE156361T1 (enExample) |
| AU (1) | AU5018693A (enExample) |
| DE (1) | DE69312947T2 (enExample) |
| DK (1) | DK0661989T3 (enExample) |
| ES (1) | ES2107051T3 (enExample) |
| GR (1) | GR3024632T3 (enExample) |
| MX (1) | MX9305729A (enExample) |
| TW (1) | TW224055B (enExample) |
| WO (1) | WO1994006452A1 (enExample) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2197258T3 (es) | 1996-01-11 | 2004-01-01 | PHARMACIA & UPJOHN COMPANY | Formulacion acuosa de liberacion prolongada que comprende el factor de liberacion de la hormona de crecimiento bovino. |
| RO119862B1 (ro) * | 1996-07-03 | 2005-05-30 | Alza Corporation | Formulare stabilă neapoasă şi procedeu pentru prepararea acesteia |
| KR100593221B1 (ko) * | 1996-07-03 | 2007-03-02 | 알자 코포레이션 | 비수성극성비양성자성펩타이드제제 |
| KR100594519B1 (ko) * | 1996-07-03 | 2007-03-02 | 앨자 코포레이션 | 비수성양성자성펩티드제제 |
| US5932547A (en) * | 1996-07-03 | 1999-08-03 | Alza Corporation | Non-aqueous polar aprotic peptide formulations |
| US5981489A (en) * | 1996-07-18 | 1999-11-09 | Alza Corporation | Non-aqueous protic peptide formulations |
| IN184589B (enExample) | 1996-10-16 | 2000-09-09 | Alza Corp | |
| US7732404B2 (en) * | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
| US6773711B2 (en) * | 2000-02-15 | 2004-08-10 | Allergan, Inc. | Botulinum toxin therapy for Hashimoto's thyroiditis |
| US6358513B1 (en) | 2000-02-15 | 2002-03-19 | Allergan Sales, Inc. | Method for treating Hashimoto's thyroiditis |
| US6524580B1 (en) | 2000-02-15 | 2003-02-25 | Allergan Sales, Inc. | Method for treating thyroid disorders |
| US6649161B1 (en) | 2000-02-22 | 2003-11-18 | Allergan, Inc. | Method for treating hypocalcemia |
| US20040170665A1 (en) * | 2000-06-02 | 2004-09-02 | Allergan, Inc. | Intravitreal botulinum toxin implant |
| US20040033241A1 (en) * | 2000-06-02 | 2004-02-19 | Allergan, Inc. | Controlled release botulinum toxin system |
| US6306423B1 (en) | 2000-06-02 | 2001-10-23 | Allergan Sales, Inc. | Neurotoxin implant |
| EP1339312B1 (en) * | 2000-10-10 | 2006-01-04 | Microchips, Inc. | Microchip reservoir devices using wireless transmission of power and data |
| KR100838219B1 (ko) * | 2001-07-13 | 2008-06-13 | 동아제약주식회사 | 인간성장호르몬의 지속적인 방출이 가능한 생분해성약학적 조성물 및 미립구 제형 |
| WO2004022033A1 (en) * | 2002-09-04 | 2004-03-18 | Microchips, Inc. | Method and device for the controlled delivery of parathyroid hormone |
| US7074425B2 (en) * | 2002-09-26 | 2006-07-11 | Bonewax, Llc | Hemostatic compositions and methods |
| MXPA05003884A (es) | 2002-10-16 | 2005-10-05 | Euro Celtique Sa | Anticuerpos que enlazan polipeptidos ca 125/0772p a celulas asociadas y metodos de uso de los mismos. |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| WO2005027960A1 (en) * | 2003-09-25 | 2005-03-31 | Cangene Corporation | Liquid human growth hormone formulation containing polyethylene glycol |
| CN105820160B (zh) | 2003-11-05 | 2019-02-12 | 萨可德生物科学公司 | 细胞粘着调节剂 |
| EP1843783B1 (en) * | 2005-01-25 | 2012-05-30 | MicroCHIPS, Inc. | Control of drug release by transient modification of local microenvironments |
| MY139088A (en) | 2005-02-21 | 2009-08-28 | Lg Life Sciences Ltd | Sustained release composition of protein drug |
| US20080311101A1 (en) * | 2005-06-10 | 2008-12-18 | Shenoy Bhami C | Method to Reduce Oxalate Concentration by Administration of Oxalate Oxidase Crystals |
| US7756524B1 (en) | 2006-01-31 | 2010-07-13 | Nextel Communications Inc. | System and method for partially count-based allocation of vocoder resources |
| US20070178138A1 (en) * | 2006-02-01 | 2007-08-02 | Allergan, Inc. | Biodegradable non-opthalmic implants and related methods |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| MX354786B (es) | 2007-06-04 | 2018-03-21 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos. |
| CA2702984C (en) * | 2007-10-19 | 2017-04-11 | Sarcode Corporation | Compositions and methods for treatment of diabetic retinopathy |
| DK2214643T3 (da) | 2007-11-02 | 2014-05-26 | Acrux Dds Pty Ltd | Transdermalt frigivelsessystem til hormoner og steroider |
| US9107815B2 (en) * | 2008-02-22 | 2015-08-18 | Allergan, Inc. | Sustained release poloxamer containing pharmaceutical compositions |
| WO2009128932A1 (en) * | 2008-04-15 | 2009-10-22 | Sarcode Corporation | Delivery of lfa-1 antagonists to the gastrointestinal system |
| CA2726917C (en) | 2008-06-04 | 2018-06-26 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP2321341B1 (en) | 2008-07-16 | 2017-02-22 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| US9314509B2 (en) | 2009-11-16 | 2016-04-19 | Ipsen Pharma S.A.S. | Pharmaceutical compositions of melanocortin receptor ligands |
| DE102009056745A1 (de) * | 2009-12-04 | 2011-06-09 | Lts Lohmann Therapie-Systeme Ag | Transdermales therapeutisches System für die Verabreichung von Peptiden |
| US20120283172A1 (en) * | 2009-12-21 | 2012-11-08 | Ambrx, Inc. | Modified porcine somatotropin polypeptides and their uses |
| BR112012015461A2 (pt) * | 2009-12-21 | 2017-01-10 | Ambrx Inc | polipeptídeos de somatotropina boviina modificados e seus usos |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| EP2790681B9 (en) | 2011-11-18 | 2023-07-26 | Regeneron Pharmaceuticals, Inc. | Method of manufacturing an extended release pharmaceutical formulation comprising polymer coated protein microparticles using spray-drying |
| UY34913A (es) * | 2012-07-17 | 2013-12-31 | Bayer New Zealand Ltd | Formaciones inyectables de antibiótico y sus métodos de aplicación |
| JP6499591B2 (ja) | 2013-02-25 | 2019-04-10 | シナジー ファーマシューティカルズ インコーポレイテッド | 結腸洗浄において用いるためのグアニル酸シクラーゼ受容体アゴニスト |
| WO2014151200A2 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| JP2016514671A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼのアゴニストおよびその使用 |
| CA2926691A1 (en) | 2013-10-10 | 2015-04-16 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of opioid induced dysfunctions |
| TW201618783A (zh) | 2014-08-07 | 2016-06-01 | 艾森塔製藥公司 | 以布魯頓(Bruton)氏酪胺酸激酶(BTK)佔據和BTK再合成速率為基礎之治療癌症、免疫和自體免疫疾病及發炎性疾病之方法 |
| CA3001346A1 (en) * | 2015-10-16 | 2017-04-20 | Regeneron Pharmaceuticals, Inc. | Stable protein compositions |
| JP2019506383A (ja) | 2016-01-11 | 2019-03-07 | シナジー ファーマシューティカルズ インコーポレイテッド | 潰瘍性大腸炎を治療するための製剤および方法 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1185340A (en) * | 1967-12-19 | 1970-03-25 | Gen Foods Corp | Water Dispersable Hydrophilic Colloid Composition. |
| US4041155A (en) * | 1974-10-29 | 1977-08-09 | American Home Products Corporation | Long acting somatostatin composition |
| US3966962A (en) * | 1975-03-27 | 1976-06-29 | The Upjohn Company | Triacetin solutions of PGE-type compounds |
| US4301175A (en) * | 1980-12-29 | 1981-11-17 | The Upjohn Company | E-Type prostaglandin compositions |
| ZA831186B (en) * | 1982-03-22 | 1983-11-30 | Upjohn Ltd | Gelled pge2/triacetin solutions |
| DE3484584D1 (de) * | 1983-10-14 | 1991-06-20 | Sumitomo Pharma | Injektionen mit verzoegerter abgabe. |
| JPS60224638A (ja) * | 1984-04-23 | 1985-11-09 | Kao Corp | 経皮吸収促進剤およびこれを含有する外用剤 |
| ES8702440A1 (es) * | 1984-10-04 | 1986-12-16 | Monsanto Co | Un procedimiento para la preparacion de una composicion de polipeptido inyectable sustancialmente no acuosa. |
| US4977140A (en) * | 1985-08-23 | 1990-12-11 | Eli Lilly And Company | Injectable sustained release formulation |
| JPS62123112A (ja) * | 1985-11-22 | 1987-06-04 | Sunstar Inc | 軟膏基剤 |
| US4917685A (en) * | 1986-05-16 | 1990-04-17 | International Minerals & Chem. Corp. | Delivery device for the administration of stabilized growth promoting hormones |
| FR2606597B1 (fr) * | 1986-11-17 | 1989-01-27 | Rhone Poulenc Sante | Nouvelle composition pour l'alimentation des ruminants contenant une substance biologiquement active et sa preparation |
| US4795641A (en) * | 1987-08-20 | 1989-01-03 | Eastman Kodak Company | Polymer blends having reverse phase morphology for controlled delivery of bioactive agents |
| US5004728A (en) * | 1988-03-11 | 1991-04-02 | The Trustees Of The University Of Pennsylvania | Methods of increasing milk yields in ruminants |
| IT1230576B (it) * | 1988-10-20 | 1991-10-28 | Angeli Inst Spa | Formulazioni farmaceutiche per via orale a liberazione selettiva nel colon |
| KR920700613A (ko) * | 1989-05-16 | 1992-08-10 | 지구르트 퓌터 | 약제제 |
| NZ234802A (en) * | 1989-08-14 | 1992-11-25 | Merck & Co Inc | Long acting injectable formulations comprising an avermectin compound and triacetin. treatment for internal and external parasites of animals |
| US5179189A (en) * | 1990-01-19 | 1993-01-12 | Nova Pharmaceutical Corporation | Fatty acid terminated polyanhydrides |
| JP3219096B2 (ja) * | 1990-05-10 | 2001-10-15 | ニコメド ファーマ エイエス | ｎ―グリコフロール類及びｎ―エチレングリコール類を含有する医薬製剤 |
| US5091185A (en) * | 1990-06-20 | 1992-02-25 | Monsanto Company | Coated veterinary implants |
| US5206219A (en) * | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
-
1993
- 1993-08-23 JP JP50808394A patent/JP3756512B2/ja not_active Expired - Fee Related
- 1993-08-23 AT AT93920157T patent/ATE156361T1/de not_active IP Right Cessation
- 1993-08-23 AU AU50186/93A patent/AU5018693A/en not_active Abandoned
- 1993-08-23 EP EP93920157A patent/EP0661989B1/en not_active Expired - Lifetime
- 1993-08-23 ES ES93920157T patent/ES2107051T3/es not_active Expired - Lifetime
- 1993-08-23 DE DE69312947T patent/DE69312947T2/de not_active Expired - Fee Related
- 1993-08-23 DK DK93920157.0T patent/DK0661989T3/da active
- 1993-08-23 WO PCT/US1993/007756 patent/WO1994006452A1/en not_active Ceased
- 1993-08-31 TW TW082107064A patent/TW224055B/zh active
- 1993-09-20 MX MX9305729A patent/MX9305729A/es not_active IP Right Cessation
-
1995
- 1995-03-20 US US08/407,327 patent/US6011011A/en not_active Expired - Fee Related
-
1997
- 1997-09-04 GR GR970402270T patent/GR3024632T3/el unknown
-
2004
- 2004-07-13 JP JP2004206098A patent/JP2004285079A/ja not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| DE69312947D1 (de) | 1997-09-11 |
| JP3756512B2 (ja) | 2006-03-15 |
| MX9305729A (es) | 1994-03-31 |
| GR3024632T3 (en) | 1997-12-31 |
| ATE156361T1 (de) | 1997-08-15 |
| WO1994006452A1 (en) | 1994-03-31 |
| AU5018693A (en) | 1994-04-12 |
| US6011011A (en) | 2000-01-04 |
| JPH08501305A (ja) | 1996-02-13 |
| EP0661989B1 (en) | 1997-08-06 |
| ES2107051T3 (es) | 1997-11-16 |
| EP0661989A1 (en) | 1995-07-12 |
| JP2004285079A (ja) | 2004-10-14 |
| TW224055B (enExample) | 1994-05-21 |
| DK0661989T3 (da) | 1998-03-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69312947T2 (de) | Proteinhaftige arzneimittel mit verzögerter wirkstoffabgabe | |
| DE60027272T2 (de) | Stabile, nichtwässrige, einphasige, biokompatible, viskose Träger und Formulierungen, die diese Träger verwenden | |
| DE69722620T2 (de) | Nicht-waessrige protische peptidzubereitungen | |
| DE69719367T2 (de) | Verfahren zur herstellung einer zusammensetzung mit verzoegerter abgabe | |
| DE69713378T2 (de) | Stabile protein- und nukleinsäure- formulierungen unter verwendung nichtwässriger, wasserfreier, aprotischer, hydrophober, nichtpolarer vehikel mit geringer reaktivität | |
| DE69102176T2 (de) | Stabile Zusammensetzungen zur parenteralen Anwendung und Verfahren zu ihrer Herstellung. | |
| DE4023134C2 (de) | Verfahren zur Herstellung einer pharmazeutischen Zubereitung in Form von Mikropartikeln | |
| DE60115005T2 (de) | Formulierungen mit verzögerter freisetzung enthaltend wachstumshormon | |
| DE69715639T2 (de) | Nicht wässrige polar-aprotische peptidzubereitung | |
| DE69329367T2 (de) | Wachstumshormon-enthaltendeproteinformulierung | |
| EP0306824B1 (de) | Stabilisierte Humanprotein-Präparate | |
| DE69727572T2 (de) | Wässrige peptidzubereitung | |
| DE3782737T3 (de) | Stabilisierung von Wachstumshormonen. | |
| DE69325256T2 (de) | Insizierbare lecithin gel | |
| DE68907066T2 (de) | Verbesserte Formulierungen mit kontrollierter Abgabe. | |
| DE69621942T2 (de) | Verbessertes herstellungsverfahren und zusammensetzung für therapeutisches cisplatin (cddp) | |
| DE3240177C2 (enExample) | ||
| DE69938452T2 (de) | Sprüh-getrocknete Insulin-Mikropartikel zur Inhalation | |
| DE69838750T2 (de) | Zeitverzögerte gelzusammensetzungen mit verlängerter wirkstoffverabreichung | |
| DE69028710T2 (de) | Arzneiabgabesystem, verfahren zu dessen herstellung sowie dessen verwendung | |
| DE69230672T2 (de) | Gonadotropin, das pharmazeutische zusammensetzungen mit sucrose stabilisator enthält | |
| DD298053A5 (de) | Verfahren zum herstellen einer stabilen zubereitung eines pharmazeutischen peptides | |
| DE69420872T2 (de) | Hgh enthaltende pharmazeutische zubereitungen | |
| DE3782117T2 (de) | Verkapselung von trh bzw. dessen analoga. | |
| DE69417397T2 (de) | Lösung, die igf-1 enthält |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |