CN1454104A - 具有刺入限制机构的物质真皮内输送针 - Google Patents
具有刺入限制机构的物质真皮内输送针 Download PDFInfo
- Publication number
- CN1454104A CN1454104A CN01811882A CN01811882A CN1454104A CN 1454104 A CN1454104 A CN 1454104A CN 01811882 A CN01811882 A CN 01811882A CN 01811882 A CN01811882 A CN 01811882A CN 1454104 A CN1454104 A CN 1454104A
- Authority
- CN
- China
- Prior art keywords
- pin
- skin
- depth
- outlet
- infusion
- 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.)
- Pending
Links
- 239000000126 substance Substances 0.000 title claims abstract description 18
- 230000035515 penetration Effects 0.000 title description 2
- 238000001802 infusion Methods 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 32
- 239000012530 fluid Substances 0.000 claims abstract description 16
- 229940088597 hormone Drugs 0.000 claims abstract description 7
- 239000005556 hormone Substances 0.000 claims abstract description 7
- 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 claims description 64
- 239000000463 material Substances 0.000 claims description 35
- 102000004877 Insulin Human genes 0.000 claims description 32
- 108090001061 Insulin Proteins 0.000 claims description 32
- 229940125396 insulin Drugs 0.000 claims description 32
- 238000012546 transfer Methods 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 3
- 230000005540 biological transmission Effects 0.000 claims description 2
- 238000003780 insertion Methods 0.000 claims 1
- 230000037431 insertion Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 25
- 229940079593 drug Drugs 0.000 abstract description 10
- 230000036407 pain Effects 0.000 abstract description 9
- 241001465754 Metazoa Species 0.000 abstract description 6
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- 230000008030 elimination Effects 0.000 abstract description 2
- 238000003379 elimination reaction Methods 0.000 abstract description 2
- 210000003491 skin Anatomy 0.000 description 42
- 238000007920 subcutaneous administration Methods 0.000 description 17
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 210000002381 plasma Anatomy 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 230000032258 transport Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 4
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 3
- 108010016076 Octreotide Proteins 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000002500 effect on skin Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 231100000241 scar Toxicity 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 229940072272 sandostatin Drugs 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037058 blood plasma level Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- -1 conmadin Chemical compound 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000012502 diagnostic product Substances 0.000 description 1
- 238000005553 drilling Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- SEGSDVUVOWIWFX-UHFFFAOYSA-N ethyl biscoumacetate Chemical compound C1=CC=C2C(=O)C(C(C=3C(C4=CC=CC=C4OC=3O)=O)C(=O)OCC)=C(O)OC2=C1 SEGSDVUVOWIWFX-UHFFFAOYSA-N 0.000 description 1
- 229960002822 ethyl biscoumacetate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004442 gravimetric analysis Methods 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960002068 insulin lispro Drugs 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229960001494 octreotide acetate Drugs 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000004203 pancreatic function Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/46—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for controlling depth of insertion
-
- 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
- A61K38/28—Insulins
-
- 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
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
- A61M5/158—Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
- A61M5/3286—Needle tip design, e.g. for improved penetration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
- A61M5/329—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles characterised by features of the needle shaft
- A61M5/3291—Shafts with additional lateral openings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
- A61M5/3295—Multiple needle devices, e.g. a plurality of needles arranged coaxially or in parallel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0038—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a channel at the side surface
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0061—Methods for using microneedles
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Medical Informatics (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Media Introduction/Drainage Providing Device (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Extraction Or Liquid Replacement (AREA)
Abstract
本发明提供一种向人体或动物体进行药物或其它物质的ID输入的改进方法。该方法将小号规格的针,特别是显微针放置在真皮内空间中,以便将物质作成散射体或采用输注方式输送到真皮内空间。现已发现,采用小号规格的针来有效输送活性物质,以防止物质泄漏到皮肤外面,并提高真皮内空间的物质吸收能力的关键之处是针的出口在皮肤内的放置和针出口露出的高度。已发现,按照本发明的方法输送的激素药物的药物动力学状况与传统的SC输送的药物动力学状况非常类似,这表明根据本发明的方法的ID给药能够获得相似的临床效果(即相似的效力),同时具有减少或消除病人疼痛的优点。将针出口放置在真皮内空间中一合适的深度,并控制流体输送的输送量和速率的输送装置能够在***漏的情况下将物质精确输送到期望位置。
Description
技术领域
本发明涉及将物质输送到皮肤内的方法和装置。
背景技术
传统的针长期以来用于经皮肤将药物或其它物质输送到人体或动物体中,并且在采用传统的针实现经皮肤的反复、有效的输送,同时减少或消除疼痛方面已卓见成效。某些真皮内的输送***完全避免使用针,并依赖于化学介质或外部驱动力,如离子电渗流或声传递(sonophoresis)来无痛穿破角质层,并经皮肤输送物质。但是,这种真皮内输送***重复性不够好,并且临床效果不稳定。
机械穿破角质层仍被认为是经皮肤给送物质的重复性最好的方法,它具有最大程度的可控制性和可信性。肌肉(IM)和皮下(SC)注射是最常用的给药途径。真皮位于角质层和表皮下方,开始于人体皮肤表面下深约60-120μm处,并且厚度约为1-2mm。然而,真皮(ID)注射很少采用,因为很难将针放置到真皮内空间的正确位置,难于维持针在真皮内空间中的位置,并且缺少许多用于ID输送药物的药物动力学曲线的知识。另外,人们基本上不了解流体在真皮组织内的吸收极限和贮存时间与药物稳定性之间的效果关系。但是,药物和其它物质的ID给送可以有一些优点。真皮内空间靠近毛细血管床,有利于物质的吸收和全身的分布,但是它又位于神经末梢网之上,这样可以减少或消除注射疼痛。另外,与目前推荐的SC给药位置(基本上限定为腹部和大腿处)相比,对于一个病人来说,ID给药有更多合适并且可接受的ID注射位置。
目前在针设计方面的改进已减少了注射的疼痛。采用较小号规格和更锋利的针减少了对皮肤的损伤,因而减少了因释放介质而引起炎症的可能。出于这方面的考虑,最好是选择显微针。显微针一般直径(width)小于0.2mm,长度小于2mm,它们通常由硅,塑料或金属制成,并且可以是空心的,以便于通过一内腔输送或采样物质(例如参见下述专利文献:US3,964,482;US5,250,023;US5,876,582;US5,591,139;US5,801,057;US5,928,207;WO96/17648)。或是针可以是实心的(例如参见US5,879,326;WO96/37256)。通过选择合适的针长度、显微针的刺入深度可以控制避免触及皮肤的神经末梢网,并减少或消除疼痛感。采用直径非常小并且非常锋利的显微针还有利于降低注射时的感觉。显微针被认为是用于机械穿孔角质层,并增加皮肤的渗透性(US5,003,987)。但是,本发明已发现,在采用显微针的情况下,仅穿破角质层对于临床上有效地进行物质的真皮内输送来说是不够的。因此,采用小号规格的针来进行真皮内输送物质,以便使物质产生有益的临床效果还受其它因素的影响。
US5,848,991公开了一种装置,该装置用于在受控状态下将药物输送到皮肤的有限深度中,该深度约为0.3-3.0mm。该专利还指出,所述装置可用于各种药物,包括激素的输送。US5,957,895也公开了一种在受控状态下输送药物的装置,其中针可刺入皮肤的深度达3mm或小于3mm。该装置的压力储液室中的流体在气压作用下,在预定的时间内渐渐地通过针被排出,例如对于输送胰岛素而言在24小时内输送完。上述专利均没有表明采用所述装置的输送能够产生临床上有益的效果。Kaushik等曾描述采用显微针将胰岛素输送到患有糖尿病的老鼠的皮肤中,从而可检测到血糖水平降低。这些作者既没有公开显微针的刺入深度,也没有给出采用这种给药方法是否能获得临床上有益的葡萄糖浓度的响应的教导。另外,现有技术中也没有表明采用这种装置能够精确输送或同一容量的重复输送。WO99/64580指出可以采用显微针以临床上相应的速率来将物质输送到皮肤中,但是它没有考虑到临床效果取决于药物物质输送的精度、数量和同一容量或质量的重复输送,以及真皮组织对该物质从药物动力学方面而言的摄取与分布。
发明内容
本发明改进了将药物或其它物质ID输送到人体或动物体内的临床应用。该方法采用小号规格的针,特别是显微针放置在真皮内空间中,以便将物质作为散射体或采用输注方式输送到真皮内空间。现已发现,采用小号规格的针来有效输送活性物质,以防止物质泄漏到皮肤外面,并提高真皮内空间的物质吸收能力的关键之处是针的出口在皮肤内的放置。根据本发明,ID输注是优选的方法,因为它仅需要较低的输送压力。这样做还减少了因流体在被吸收前淤积在皮肤内而使内部压力增高,从而使物质流失到皮肤表面的数量。也就是说,输注使物质最少量地渗出到组织之外。输注还降低了肿胀疼痛和组织的肿胀,并且与散射体剂量相比还降低了内部压力。已发现,按照本发明的方法输送的激素药物的药物动力学状况与传统的SC输送的药物动力学状况非常类似,这表明根据本发明的方法的ID给药能够获得相似的临床效果(即相似的效力),同时具有减少或消除病人疼痛的优点。将针出口放置在真皮内空间中一合适的深度,并控制流体输送的输出量和速率的输送装置能够在***漏的情况下将物质精确输送到期望位置。
附图说明
图1示出了例1的结果,表示在SC输注和ID输注胰岛素时的血浆胰岛素水平。
图2示出了例1的结果,表示在SC输注和ID输注胰岛素时的血糖水平。
图3示出了例1的结果,表示在SC输注和ID输注时的PTH血浆PTH水平。
图4示出了例2的结果,表示在以2U/hr进行胰岛素的SC输注和ID输注时的血浆胰岛素水平。
图5示出了例2的结果,表示在以2U/hr进行胰岛素的SC输注和ID输注时的血浆中葡萄糖水平。
具体实施方式
本发明提供借助刺入皮肤直至真皮内空间的深度的装置将药物或其它物质输送到人体或动物体对象中。药物或物质通过装置的一根或多根空心针被给送到真皮内空间中。已发现,按照本发明的方法输注的物质所呈现出的药物动力学状况与观察到的相同物质通过SC注射给送时的状况相似,但ID注射基本上为无痛的。该方法特别适合应用到激素治疗中,包括胰岛素和副甲状腺激素(PTH)的给药。
按照本发明,用于ID给药的注射装置不是发明关键,只要它刺入治疗对象的皮肤中的深度足以达到真皮内空间,但不穿过它即可。在大多数情况下,装置将刺入皮肤约0.5-3mm深,最好约为1-2mm。装置可包括传统的注射针、所有公知类型的导管或显微针,采用单根针或多根针阵列。这里所用的“针”或“针组”将包含所有这种针状的结构。针最好为小号规格的,如显微针(即约小于25号规格;一般为约27-35号规格)。针刺入的深度可由医生人工控制,可采用或不采用指示已达到期望深度的辅助指示机构。但是,该装置优选有一个结构性的机构用于限制刺入皮肤达到真皮内空间的深度。这种结构性机构可包括限制用于刺入的针或导管的长度,这样它的深度不会超过真皮内空间的深度。实现上述目的最常采用的方式是采用加宽区域或以针的轴相关联的“毂”,或者对针阵列来说可采用针附着在其上的背衬结构或平台(例如参见US5,879,326;WO96/37155;WO96/37256)。显微针特别适于实现上述目的,因为显微针的长度在制造过程中易于改变,并且显微针通常制造成其长度小于1mm。显微针也十会锋利,并且规格很小(一般约为33号规格或更小),因而在注射或输注时更能减少疼痛和其它感觉。它们可作为单个的单腔显微针用于本发明中,或者多根显微针组装成或构造成线性阵列或二维阵列,以便在给定的时间内提高输送速率或物质的输送数量。显微针可与其它部件,例如夹具和外壳等一起构成多种装置,其中所述外壳也可用于限制刺入或进入导管组的深度。本发明的装置也可包括一个储液室,以便在输送或泵送或其它机构输注物质前盛装物质,从而在压力作用下输送药物或其它物质。另外,罩住显微针的装置可与这些附加部件外部连接。
已发现,真皮内给药方案的某些特征是获得具有临床效果的药物动力学状况和获得精确剂量的基础。首先,已发现皮肤内针出口的放置明显影响这些参数。具有一斜面的较小号规格的针的出口具有相对较大的露出高度(出口的垂直“抬起”)。尽管针尖可以放置在真皮内空间中一定深度,但针出口的较大露出高度使得被输送的物质淤积于靠近皮肤表面的很浅深度处。这样,物质会因为皮肤本身的反压力和注射或输注的堆积流体所产生的压力作用而渗出皮肤。例如,通常认定200μm的显微针为合适的通过皮肤输送物质的装置。然而,我们已发现,即使针出口位于这种显微针(无任何斜面)的尖端,物质也会淤积在很浅的深度范围内,以使皮肤能够环绕着针密封,并且物质很容易渗出到皮肤表面上。例如这些较短的显微针仅用于刺入皮肤,从临床应用上说不能给予足够的剂量控制。相反,本发明的显微针具有足以刺入真皮内空间的长度(“刺入深度”),并且针出口在真皮内空间的深度(“出口深度”)使得皮肤能够环绕针密封,以抵抗迫使输送物质朝皮肤表面渗出的反作用力。总的来说,针的长度不超过约2mm,优选为约300μm至2mm,最优选的是约500μm至1mm长。当针***到皮肤中时,针出口的深度一般约为250μm至2mm,优选深度约为750μm至1.5mm,最优选的是约为1mm深。针出口的露出高度和在真皮内空间中该出口的深度影响着皮肤环绕针密封的程度。这就是说,针出口的深度较深时,即使针出口的露出高度较高也能具有有效的密封,而当放置在真皮内空间的深度较浅时,同样的露出高度则不能具有有效的密封。一般来说,针出口的露出高度将从0至约1mm,优选从0至约300μm。露出高度为0的针出口无斜面,并且位于针的尖端。在这种情况下,出口的深度与针刺入的深度相同。由一斜面或者通过在针的侧面设有开口而形成的针的出口具有可测出的露出高度。
其次,已发现应仔细控制注射或输注的压力,因为在ID给药时可呈现高的反压力。现有技术中所用的气压驱动装置易于偏离输送速率。因此,优选输送物质的方法在液体表面上施加一恒定的压力,因为这样能够提供较恒定的输送速率,该恒定的输送速率是使吸收最优化,并且获得期望的药物动力学效果。控制输送速率和输送量还为了防止在输送点处形成伤痕,并防止产生能够将针推出皮肤外的反压力。普通技术人员仅凭经验即可根据所选物质确定合适的输送速率和输送量,以获得上述效果。这就是说,总的来说当伤痕的尺寸增加时,对输注而言,其输送速率增加;对散射体注射而言,其输送量增加。然而,显微针的尺寸和数量以及它们放置时的靠近程度可以调节,以便在不影响皮肤上的效果和针在皮肤中的稳定性的前提下维持期望的输送速率或输送量。例如,增加显微针阵列装置中针之间的距离,或采用较小直径的针来降低皮肤中未吸收流体所产生的压力。这种压力会引起伤痕,并将针推出到皮肤之外。选择直径较小的针并且增加多根针之间的距离能够在输送速率增加或输送量增大的情况下使吸收速度增快。另外,我们已发现,ID输注或注射与传统的SC给药相比,通常能够使血浆药物水平较高,特别是对那些易于在体内降解或从体内清除出的药物而言。这样,在某些情况下可以允许借助ID通道,通过显微针来较少量地给送物质,进而可以较少考虑产生气泡和反压力的问题。
本发明实现的给药方法包括将药物或其它物质输送到人体或动物体对象的散射体输送或输注两种方式。散射体剂量为在相对较短的时间段内,一般在少于5-10分钟内以单一体积单元输送的单一剂量。输注给药包括以所选速率(可以是恒定的或是变化的),在相对较长的时间段内,一般为在大于约5-10分钟的时间内给送一种流体。根据本发明输送物质时,针放置在真皮内空间中,物质通过针的内腔输送到真皮内空间中,该物质可以局部起作用或被血流吸收并分布到全身。针可以与一盛装有输送物质的储液室相连。从储液室到真皮内空间的输送可以是被动的(不对输送物质施加外力),也可以是主动的(通过施加外力)。优选的压力产生装置例如包括泵、注射器、弹性膜、渗透压或Belleville弹簧或洗涤器。例如参见US5,957,895;US5,250,023;WO96/17648;WO98/11937;WO99/03521。如果需要,可以通过压力产生装置来变化控制物质输送速率。这样,物质进入到真皮内空间并被吸收一定的量,并且物质以足以产生临床有益效果的速度进入。“临床有益效果”是指物质的给送能够产生临床上有益的生物反应。例如,防止或治疗一种疾病或病症为一种临床上有益的效果,如临床上适当控制血糖水平(胰岛素),临床上适当处理激素缺乏(PTH,生长激素),保护性免疫的表达(疫苗),或临床上适当处理毒性(抗毒素)。作为另一个例子,临床上有益的效果还包括控制疼痛(例如采用triptans,类***,止痛剂,麻醉剂等),血栓症(采用肝磷脂,香豆定,苄丙酮香豆素等)以及控制或消除传染(采用抗生素)。
例1
胰岛素ID输注的例子为采用不锈钢30号规格的针,其尖端部分弯成90度角,这样用于刺入皮肤的可用长度为1-2mm。当将针***皮肤中时,针出口(针的尖端)的在皮肤中的深度为1.7-2.0mm,针出口的露出高度为1.0-1.2mm。针在输送装置中的构成与US5,957,895公开的内容相似,储液室中盛装的胰岛素的输注压力由塑料Belleville弹簧提供,经重量分析测得的流动速率为9U/hr(90uL/hr)。采用MiniMed507胰岛素输注泵和Disetronic SC导管组来设定相应于SC受控输注的流动速率。输注醋酸奥曲肽,以抑制猪的基础胰岛素分泌(Sandostatin,Sandoz Pharmaceuticals,East Hanover,NJ),同时输注10%的葡萄糖,使之产生高血糖症。经过两小时的诱导和基本的时间之后,输注胰岛素两小时,然后经过三小时的清除时间。采用公知的放射免疫测定法(Coat-A-Countinsulin,Diagnostic Products Corporation,LosAngeles,CA)来确定血浆胰岛素水平,并采用市售监测器(Accu-chekAdvantage,Boehringer Mannheim Corp,Indianapolis,IN)来测量血糖值。图1和图2示出了重量规度的血浆胰岛素水平和相应的血糖值。数据表明,通过ID途径和传统的SC途径输注时具有相似的血浆胰岛素水平和起作用时间。两者之间血糖降低响应也类似。尽管给药率为9U/hr与医学中的常规用法相比较高,但这些结果也表明,真皮组织能够在采用上述途径输注的情况下很容易吸收和分布药物。
类似的试验还采用人体副甲状腺激素1-34(PTH)进行。在四小时的时间内输注PTH,然后进行两小时的清除。通过Harvard注射泵来控制流速。采用“捏起”技术,通过***到皮肤侧面的SC空间的标准31号规格针来控制SC输注。ID输注通过前述弯曲的30号规格的针。以75uL/hr的速率输注0.64mg/mL的PTH溶液。图3示出了重量规度的PTH血浆胰岛素水平。该数据表明,该给药途径对于附加激素药物来说是有效的,并且事实上ID输注对于易于在体内被生物降解或清除的药物来说能够提供较高的血浆水平。
例2
ID胰岛素输注以猪为例,采用与标准导管相连的空心硅显微针。导管与MiniMed507胰岛素输注泵相接,以控制流体的输送。
空心单腔显微针(总长为2mm,200*100um OD,相应于33号规格)的出口距尖端1.0μm(100μm的露出高度),由公知的工艺制成(US5,928,207),并与通常用于胰岛素输注中的微孔导管(Disetronic)相匹配。显微针的远端放置到塑料导管中,并用环氧树脂粘接,形成深度限制毂。针出口位于超过环氧毂约1mm的位置,这样将针出口刺入皮肤内的深度限定为约1mm,该位置相应于猪的真皮内空间深度。肉眼观察确定明显的流体流动通路,并观察在标准1cc注射器产生的压力下无障碍。导管通过导管出口处的组装的Luer连接器与外部胰岛素输注泵(MiniMed507)相连。
泵内充有HumalogTM(LisPro)胰岛素(Lilly),并且根据制造商的说明,导管和显微针预先充有胰岛素。通过IV输注向麻醉猪给送Sandostatin溶液,以抑制基础胰腺功能和胰岛素分泌。经过适当时间的诱导和基本的采样之后,预先充有胰岛素的显微针垂直***到动物侧腹的皮肤表面中,直至毂使之停止刺入。胰岛素的输注以2U/hr的速率开始,并持续4.5小时。定时取出血样,并采用例1中的方法分析血清胰岛素浓度和血糖值。输注前的原始的胰岛素水平为该化验基础检测水平,如图4所示。输注开始以后,血清胰岛素水平呈现为相应于预定输注速率而增高。血糖水平也呈现为相应于反相控制(NC)而相应降低,这种降低与传统SC输注(图5)所观察到的类似。
在该实验中,显微针表现为能够充分刺破皮肤阻挡物,并以药学上相应速率来向体内输送药物。胰岛素的ID输注表现为是药物动力学上可接受的给药途径。这些数据表明,按照本发明的方法,在人体内以ID给送激素或其它药物会取得药理学上的成功效果。
Claims (24)
1.一种将物质输送到皮肤中的方法,包括采用***到真皮内空间的小号规格的针将物质输送到皮肤内的真皮内空间中,其中针的出口***到皮肤中一定深度,从而基本上防止物质泄漏到皮肤表面上。
2.如权利要求1的方法,其中针从包括显微针、导管针和注射针的一组中选择。
3.如权利要求1的方法,其中***单根针。
4.如权利要求1的方法,其中***多根针。
5.如权利要求1的方法,其中物质为液体,通过直接作用在该液体上的压力被输送。
6.如权利要求1的方法,其中输送的是激素。
7.如权利要求6的方法,其中激素包括从胰岛素和PTH的一组中选择。
8.如权利要求1的方法,其中物质被输注。
9.如权利要求1的方法,其中物质以散射体方式被注入。
10.如权利要求1的方法,其中针的长度约为300μm至2mm。
11.如权利要求10的方法,其中针的长度约为500μm至1mm。
12.如权利要求1的方法,其中当针***时,针出口的深度约为250μm至1mm。
13.如权利要求12的方法,其中当针***时,针出口的深度约为750μm至1.5mm。
14.如权利要求12的方法,其中针出口的露出高度约为0至1mm。
15.如权利要求14的方法,其中针出口的露出高度约为0至300μm。
16.如权利要求1的方法,其中通过配置多根针、针的直径或针的数量来控制输送速率或输送容量。
17.一种将物质真皮内输送到皮肤中的针,包括用于限制针刺入皮肤和针出口位置的装置,这样当针***到皮肤中时,***深度由刺入限制装置确定,从而基本上防止物质泄漏到皮肤表面。
18.如权利要求17的针,其中当针***到皮肤中时,针出口的深度约为500μm至2mm。
19.如权利要求18方法,其中当针***到皮肤中时,针出口的深度约为750μm至1.5mm。
20.如权利要求1 7的针,其长度约为300μm至2mm。
21.如权利要求20的针,其长度约为500μm至1mm。
22.如权利要求17的针,该针包含在一用具中,该用具包括一个与所述针流体连通的储液室。
23.如权利要求22的针,该针包含在一用具中,该用具还包括一个压力产生装置,用于通过所述针输送物质。
24.如权利要求23的针,其中压力产生装置提供可变化地控制物质的输送速率。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/606,909 | 2000-06-29 | ||
US09/606,909 US8465468B1 (en) | 2000-06-29 | 2000-06-29 | Intradermal delivery of substances |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1454104A true CN1454104A (zh) | 2003-11-05 |
Family
ID=24430006
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN01811892A Pending CN1438905A (zh) | 2000-06-29 | 2001-06-29 | 向真皮输送物质的显微针 |
CN01811882A Pending CN1454104A (zh) | 2000-06-29 | 2001-06-29 | 具有刺入限制机构的物质真皮内输送针 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN01811892A Pending CN1438905A (zh) | 2000-06-29 | 2001-06-29 | 向真皮输送物质的显微针 |
Country Status (16)
Country | Link |
---|---|
US (13) | US8465468B1 (zh) |
EP (5) | EP1880743A1 (zh) |
JP (2) | JP2004501725A (zh) |
KR (2) | KR100870345B1 (zh) |
CN (2) | CN1438905A (zh) |
AT (4) | ATE536906T1 (zh) |
AU (6) | AU7585301A (zh) |
BR (2) | BR0112313A (zh) |
CA (2) | CA2413798C (zh) |
CY (3) | CY1107458T1 (zh) |
DE (3) | DE60115897T2 (zh) |
DK (4) | DK1925333T3 (zh) |
ES (4) | ES2250437T3 (zh) |
MX (2) | MXPA03000134A (zh) |
PT (3) | PT1296740E (zh) |
WO (2) | WO2002002178A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103687643A (zh) * | 2011-07-27 | 2014-03-26 | 久光制药株式会社 | 施放器 |
CN105073180A (zh) * | 2013-03-22 | 2015-11-18 | 3M创新有限公司 | 包括计数器组件的微针施用装置 |
Families Citing this family (97)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060002949A1 (en) | 1996-11-14 | 2006-01-05 | Army Govt. Of The Usa, As Rep. By Secretary Of The Office Of The Command Judge Advocate, Hq Usamrmc. | Transcutaneous immunization without heterologous adjuvant |
US8465468B1 (en) | 2000-06-29 | 2013-06-18 | Becton, Dickinson And Company | Intradermal delivery of substances |
US20020156453A1 (en) * | 1999-10-14 | 2002-10-24 | Pettis Ronald J. | Method and device for reducing therapeutic dosage |
US20020095134A1 (en) * | 1999-10-14 | 2002-07-18 | Pettis Ronald J. | Method for altering drug pharmacokinetics based on medical delivery platform |
US20040175360A1 (en) * | 2000-06-29 | 2004-09-09 | Pettis Ronald J. | Method for altering drug pharmacokinetics based on medical delivery platform |
US20050008683A1 (en) * | 2000-06-29 | 2005-01-13 | Becton Dickinson And Company | Method for delivering interferons to the intradermal compartment |
DE60239594D1 (de) * | 2001-02-23 | 2011-05-12 | Glaxosmithkline Biolog Sa | Influenza vakzinzusammensetzungen zur intradermaler verabreichung |
WO2002083232A1 (en) * | 2001-04-13 | 2002-10-24 | Becton, Dickinson And Company | Methods and devices for administration of substances into the intradermal layer of skin for systemic absorption |
US20050010193A1 (en) * | 2002-05-06 | 2005-01-13 | Laurent Philippe E. | Novel methods for administration of drugs and devices useful thereof |
BR0210628A (pt) * | 2001-06-29 | 2004-08-10 | Becton Dickinson Co | Liberação intradérmica de vacinas e agentes terapêuticos genéticos via microcânula |
WO2003022330A2 (en) | 2001-09-12 | 2003-03-20 | Becton, Dickinson And Company | Microneedle-based pen device for drug delivery and method for using same |
US20040120964A1 (en) * | 2001-10-29 | 2004-06-24 | Mikszta John A. | Needleless vaccination using chimeric yellow fever vaccine-vectored vaccines against heterologous flaviviruses |
US7004928B2 (en) * | 2002-02-08 | 2006-02-28 | Rosedale Medical, Inc. | Autonomous, ambulatory analyte monitor or drug delivery device |
CA2475573C (en) | 2002-02-11 | 2013-03-26 | Antares Pharma, Inc. | Intradermal injector |
DE20302715U1 (de) * | 2002-02-19 | 2003-09-04 | Interdigital Technology Corp W | Vorrichtung zur Realisierung von Beeinflussungskriterien für binäre Entscheidungen, die von einer Benutzervorrichtung (UE) in der drahtlosen Kommunikation zur Verbesserung des Schutzes verwendet wird |
CN1655834A (zh) * | 2002-05-06 | 2005-08-17 | 贝克顿·迪金森公司 | 用于控制药代动力学的方法和装置 |
US20060264886A9 (en) * | 2002-05-06 | 2006-11-23 | Pettis Ronald J | Method for altering insulin pharmacokinetics |
US7338465B2 (en) * | 2002-07-02 | 2008-03-04 | Patton Medical Devices, Lp | Infusion device and method thereof |
US9955994B2 (en) | 2002-08-02 | 2018-05-01 | Flowcardia, Inc. | Ultrasound catheter having protective feature against breakage |
US7335180B2 (en) | 2003-11-24 | 2008-02-26 | Flowcardia, Inc. | Steerable ultrasound catheter |
WO2004020014A2 (en) * | 2002-08-30 | 2004-03-11 | Becton, Dickinson And Company | Method of controlling pharmacokinetics of immunomodulatory compounds |
US9486581B2 (en) | 2002-09-11 | 2016-11-08 | Becton, Dickinson And Company | Injector device with force lock-out and injection rate limiting mechanisms |
WO2005061041A1 (en) | 2002-10-11 | 2005-07-07 | Becton, Dickinson And Company | Insulin delivery system with sensor |
US20050163711A1 (en) * | 2003-06-13 | 2005-07-28 | Becton, Dickinson And Company, Inc. | Intra-dermal delivery of biologically active agents |
DE10330094B4 (de) * | 2003-07-03 | 2008-04-17 | Disetronic Licensing Ag | Vorrichtung zur Verabreichung eines flüssigen Produkts |
CA2536669A1 (en) * | 2003-08-26 | 2005-03-17 | Becton, Dickinson And Company | Methods for intradermal delivery of therapeutics agents |
US7758510B2 (en) | 2003-09-19 | 2010-07-20 | Flowcardia, Inc. | Connector for securing ultrasound catheter to transducer |
US8029454B2 (en) | 2003-11-05 | 2011-10-04 | Baxter International Inc. | High convection home hemodialysis/hemofiltration and sorbent system |
WO2005091922A2 (en) * | 2004-03-03 | 2005-10-06 | Becton, Dickinson And Company | Methods and devices for improving delivery of a substance to skin |
US20050256182A1 (en) * | 2004-05-11 | 2005-11-17 | Sutter Diane E | Formulations of anti-pain agents and methods of using the same |
EP1744683B1 (en) | 2004-05-13 | 2016-03-16 | Alza Corporation | Apparatus and method for transdermal delivery of parathyroid hormone agents |
US7591806B2 (en) * | 2004-05-18 | 2009-09-22 | Bai Xu | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances |
EP1786580B1 (en) | 2004-08-16 | 2010-12-01 | Functional Microstructures Limited | Method of producing a microneedle or microimplant |
ES2908027T3 (es) | 2005-01-24 | 2022-04-27 | Antares Pharma Inc | Un inyector con jeringa precargada |
US7645264B2 (en) | 2005-04-11 | 2010-01-12 | Becton, Dickinson And Company | Injection device with secondary reservoir |
US8048017B2 (en) * | 2005-05-18 | 2011-11-01 | Bai Xu | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances |
US8043250B2 (en) * | 2005-05-18 | 2011-10-25 | Nanomed Devices, Inc. | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances |
RU2440831C2 (ru) * | 2005-08-22 | 2012-01-27 | Паттон Медикал Дивайсиз, Лп | Устройства, системы и методы введения жидкости |
RU2424003C2 (ru) | 2005-11-03 | 2011-07-20 | Паттон Медикал Дивайсиз, Лп | Устройства, системы и способы доставки жидкостей |
US7842008B2 (en) | 2005-11-21 | 2010-11-30 | Becton, Dickinson And Company | Intradermal delivery device |
US20090099502A1 (en) | 2006-04-07 | 2009-04-16 | Hisamitsu Pharmaceutical Co., Inc. | Microneedle Device And Transdermal Administration Device Provided With Microneedles |
WO2007131013A1 (en) | 2006-05-03 | 2007-11-15 | Antares Pharma, Inc. | Two-stage reconstituting injector |
WO2007131025A1 (en) | 2006-05-03 | 2007-11-15 | Antares Pharma, Inc. | Injector with adjustable dosing |
EP2041214A4 (en) | 2006-07-10 | 2009-07-08 | Medipacs Inc | SUPERELASTIC EPOXY HYDROGEL |
US10525246B2 (en) | 2006-12-22 | 2020-01-07 | Nanomed Skincare, Inc. | Microdevice and method for transdermal delivery and sampling of active substances |
US20080214987A1 (en) * | 2006-12-22 | 2008-09-04 | Nanomed Devices, Inc. | Microdevice And Method For Transdermal Delivery And Sampling Of Active Substances |
AU2008263970B2 (en) * | 2007-06-14 | 2014-01-30 | Crucell Switzerland Ag | Intradermal influenza vaccine |
EP2227635A2 (en) | 2007-12-03 | 2010-09-15 | Medipacs, Inc. | Fluid metering device |
US8814834B2 (en) | 2008-03-10 | 2014-08-26 | Antares Pharma, Inc. | Injector safety device |
AU2009279719B2 (en) | 2008-08-05 | 2015-07-23 | Antares Pharma, Inc. | Multiple dosage injector |
US8702677B2 (en) | 2008-10-31 | 2014-04-22 | Warsaw Orthopedic, Inc. | Device and method for directional delivery of a drug depot |
EP2352515A4 (en) * | 2008-11-03 | 2012-04-25 | Bayer Healthcare Llc | METHOD FOR TREATING HEMOPHILIA |
KR20110086854A (ko) * | 2008-11-18 | 2011-08-01 | 쓰리엠 이노베이티브 프로퍼티즈 컴파니 | 중공 마이크로니들 어레이 및 방법 |
AU2010226442A1 (en) | 2009-03-20 | 2011-10-13 | Antares Pharma, Inc. | Hazardous agent injection system |
US8715223B2 (en) | 2009-07-22 | 2014-05-06 | Warsaw Orthopedic, Inc. | Device and method for delivery of a drug depot near the nerve |
WO2011032011A1 (en) | 2009-09-10 | 2011-03-17 | Medipacs, Inc. | Low profile actuator and improved method of caregiver controlled administration of therapeutics |
US9199034B2 (en) * | 2009-11-09 | 2015-12-01 | Becton, Dickinson And Company | Drug delivery devices, systems, and methods |
US8454975B1 (en) | 2010-01-11 | 2013-06-04 | Elizabeth VanderVeer | Method for enhancing skin appearance |
US9500186B2 (en) | 2010-02-01 | 2016-11-22 | Medipacs, Inc. | High surface area polymer actuator with gas mitigating components |
US8668675B2 (en) | 2010-11-03 | 2014-03-11 | Flugen, Inc. | Wearable drug delivery device having spring drive and sliding actuation mechanism |
WO2012149136A1 (en) | 2011-04-26 | 2012-11-01 | The Board Of Trustees Of The Leland Stanford Junior University | Production and delivery of a stable collagen |
US9220660B2 (en) | 2011-07-15 | 2015-12-29 | Antares Pharma, Inc. | Liquid-transfer adapter beveled spike |
US8496619B2 (en) | 2011-07-15 | 2013-07-30 | Antares Pharma, Inc. | Injection device with cammed ram assembly |
US20130211289A1 (en) * | 2012-01-25 | 2013-08-15 | Tasso, Inc. | Handheld Device for Drawing, Collecting, and Analyzing Bodily Fluid |
EP4327849A3 (en) | 2012-03-06 | 2024-04-24 | Antares Pharma, Inc. | Prefilled syringe with breakaway force feature |
EP2847249A4 (en) | 2012-03-14 | 2016-12-28 | Medipacs Inc | SMART POLYMER MATERIALS WITH EXCESSIVE REACTIVE MOLECULES |
WO2013151767A1 (en) * | 2012-04-02 | 2013-10-10 | Medtronic, Inc. | Therapy for kidney disease and/or heart failure by intradermal infusion |
JP6457383B2 (ja) | 2012-04-06 | 2019-01-23 | アンタレス・ファーマ・インコーポレーテッド | テストステロン組成物の針支援式ジェット注入投与 |
US9364611B2 (en) | 2012-05-07 | 2016-06-14 | Antares Pharma, Inc. | Needle assisted jet injection device having reduced trigger force |
RU2640564C2 (ru) | 2012-08-02 | 2018-01-09 | Бард Периферэл Васкьюлар | Ультразвуковая катетерная система |
DK3659647T3 (da) | 2013-02-11 | 2024-04-22 | Antares Pharma Inc | Nålestøttet jetinjektionsindretning med reduceret udløserkraft |
JP6030803B2 (ja) | 2013-03-11 | 2016-11-24 | アンタレス・ファーマ・インコーポレーテッド | ピニオンシステムを有する用量注射器 |
WO2014165136A1 (en) | 2013-03-12 | 2014-10-09 | Antares Pharma, Inc. | Constant volume prefilled syringes and kits thereof |
JP6691041B2 (ja) | 2013-06-18 | 2020-04-28 | イネイブル インジェクションズ、インコーポレイテッド | バイアル移送と注射の器具と方法 |
EP3134110A1 (en) * | 2014-04-25 | 2017-03-01 | Sanofi | New administration routes of insulin, insulin analogs or derivatives of insulin |
US9775978B2 (en) | 2014-07-25 | 2017-10-03 | Warsaw Orthopedic, Inc. | Drug delivery device and methods having a retaining member |
US9764122B2 (en) | 2014-07-25 | 2017-09-19 | Warsaw Orthopedic, Inc. | Drug delivery device and methods having an occluding member |
EP3248634B1 (en) * | 2015-01-20 | 2021-10-27 | Terumo Kabushiki Kaisha | Injection needle assembly and injector provided therewith for injecting drug solution into upper layer of skin |
US10765361B2 (en) * | 2015-03-02 | 2020-09-08 | Verily Life Sciences Llc | Automated sequential injection and blood draw |
RU2719584C2 (ru) * | 2015-04-21 | 2020-04-21 | Норт Каролина Стейт Юниверсити | Глюкозочувствительная система доставки инсулина с использованием чувствительных к гипоксии нанокомпозитов |
EP3352814B1 (en) * | 2015-09-22 | 2024-04-10 | Thomas Jefferson University | Continuous subcutaneous insulin infusion catheter |
WO2017060899A2 (en) | 2015-10-05 | 2017-04-13 | E3D Agricultural Cooperative Association Ltd. | Infusion pump device and method for use thereof |
US10076650B2 (en) | 2015-11-23 | 2018-09-18 | Warsaw Orthopedic, Inc. | Enhanced stylet for drug depot injector |
EP3832661A1 (en) * | 2015-12-03 | 2021-06-09 | UNL Holdings LLC | Systems and methods for controlled drug delivery pumps |
EP3429663B1 (en) * | 2016-03-15 | 2020-07-15 | Amgen Inc. | Reducing probability of glass breakage in drug delivery devices |
US9827369B2 (en) | 2016-03-16 | 2017-11-28 | Baxter International Inc. | Percutaneous administration device and method for injecting medicinal substances |
USD802757S1 (en) | 2016-06-23 | 2017-11-14 | Warsaw Orthopedic, Inc. | Drug pellet cartridge |
US10434261B2 (en) | 2016-11-08 | 2019-10-08 | Warsaw Orthopedic, Inc. | Drug pellet delivery system and method |
WO2018096534A1 (en) | 2016-11-22 | 2018-05-31 | Sorrel Medical Ltd. | Apparatus for delivering a therapeutic substance |
US20180140321A1 (en) | 2016-11-23 | 2018-05-24 | C. R. Bard, Inc. | Catheter With Retractable Sheath And Methods Thereof |
US11596726B2 (en) | 2016-12-17 | 2023-03-07 | C.R. Bard, Inc. | Ultrasound devices for removing clots from catheters and related methods |
US10582983B2 (en) | 2017-02-06 | 2020-03-10 | C. R. Bard, Inc. | Ultrasonic endovascular catheter with a controllable sheath |
US10413658B2 (en) | 2017-03-31 | 2019-09-17 | Capillary Biomedical, Inc. | Helical insertion infusion device |
CN109972116B (zh) * | 2017-12-28 | 2021-03-23 | 深圳先进技术研究院 | 金刚石管及其制备方法 |
EP3744368A1 (en) | 2018-10-05 | 2020-12-02 | Sorrel Medical Ltd. | Triggering sequence |
US20220401355A1 (en) * | 2021-05-13 | 2022-12-22 | University Of Washington | Transdural Drug Delivery System |
CN114281448A (zh) * | 2021-12-07 | 2022-04-05 | 维沃移动通信有限公司 | 应用程序控制方法、装置及电子设备 |
Family Cites Families (108)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US394482A (en) * | 1888-12-11 | Triple-expansion engine | ||
US2619962A (en) | 1948-02-19 | 1952-12-02 | Res Foundation | Vaccination appliance |
US3964482A (en) | 1971-05-17 | 1976-06-22 | Alza Corporation | Drug delivery device |
BE795384A (fr) * | 1972-02-14 | 1973-08-13 | Ici Ltd | Pansements |
US4270537A (en) | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
US4655762A (en) | 1980-06-09 | 1987-04-07 | Rogers Phillip P | Ambulatory dialysis system and connector |
FR2524321A1 (fr) | 1982-03-30 | 1983-10-07 | Denance Raymond | Dispositif d'injection " manuelle ou mecanique " a usage medical et veterinaire |
US4440207A (en) | 1982-05-14 | 1984-04-03 | Baxter Travenol Laboratories, Inc. | Antibacterial protective cap for connectors |
IE53703B1 (en) | 1982-12-13 | 1989-01-18 | Elan Corp Plc | Drug delivery device |
CA1248832A (en) | 1985-07-22 | 1989-01-17 | Francesco Peluso | Antibacterial closure system |
CA1283827C (en) * | 1986-12-18 | 1991-05-07 | Giorgio Cirelli | Appliance for injection of liquid formulations |
US6056716A (en) * | 1987-06-08 | 2000-05-02 | D'antonio Consultants International Inc. | Hypodermic fluid dispenser |
AU614092B2 (en) | 1987-09-11 | 1991-08-22 | Paul Max Grinwald | Improved method and apparatus for enhanced drug permeation of skin |
US5007501A (en) | 1989-09-01 | 1991-04-16 | Baston Peter J | Apparatus for facilitating the internal inspection and repair of large pressure vessels |
EP0429842B1 (en) | 1989-10-27 | 1996-08-28 | Korea Research Institute Of Chemical Technology | Device for the transdermal administration of protein or peptide drug |
US5098389A (en) | 1990-06-28 | 1992-03-24 | Becton, Dickinson And Company | Hypodermic needle assembly |
US5505694A (en) | 1990-08-22 | 1996-04-09 | Tcnl Technologies, Inc. | Apparatus and method for raising a skin wheal |
US5156591A (en) | 1990-12-13 | 1992-10-20 | S. I. Scientific Innovations Ltd. | Skin electrode construction and transdermal drug delivery device utilizing same |
US5279544A (en) | 1990-12-13 | 1994-01-18 | Sil Medics Ltd. | Transdermal or interdermal drug delivery devices |
TW279133B (zh) * | 1990-12-13 | 1996-06-21 | Elan Med Tech | |
US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
ES2027923A6 (es) | 1991-01-30 | 1992-06-16 | Segura Badia Marcelo | Conexion desinfectante para tubos de cateteres y similares. |
US5484417A (en) * | 1991-04-19 | 1996-01-16 | Biotime, Inc. | Microcannula |
SE9102652D0 (sv) | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
US5242425A (en) | 1991-11-14 | 1993-09-07 | Gish Biomedical, Inc. | Antiseptic catheter coupling septum |
US5328483A (en) * | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
US5279552A (en) * | 1993-01-11 | 1994-01-18 | Anton Magnet | Intradermal injection device |
IE68890B1 (en) | 1993-04-08 | 1996-07-24 | Elan Med Tech | Intradermal delivery device |
US5567495A (en) | 1993-08-06 | 1996-10-22 | The Trustees Of Columbia University In The City Of New York | Infection resistant medical devices |
CA2132277C (en) * | 1993-10-22 | 2005-05-10 | Giorgio Cirelli | Injection device |
US5997501A (en) * | 1993-11-18 | 1999-12-07 | Elan Corporation, Plc | Intradermal drug delivery device |
US5536258A (en) | 1994-02-14 | 1996-07-16 | Fresenius Usa, Inc. | Antibacterial medical tubing connector |
IL113010A0 (en) | 1994-03-31 | 1995-10-31 | Pharmacia Ab | Pharmaceutical formulation comprising factor VIII or factor ix with an activity of at least 200 IU/ml and an enhancer for improved subcutaneous intramuscular or intradermal administration |
JPH07299143A (ja) * | 1994-05-09 | 1995-11-14 | Kenji Tsubota | 医科用注射針 |
US5591139A (en) | 1994-06-06 | 1997-01-07 | The Regents Of The University Of California | IC-processed microneedles |
US5540657A (en) * | 1994-07-15 | 1996-07-30 | Collagen Corporation | Delivery device for injectable materials |
US5582591A (en) * | 1994-09-02 | 1996-12-10 | Delab | Delivery of solid drug compositions |
IE72524B1 (en) | 1994-11-04 | 1997-04-23 | Elan Med Tech | Analyte-controlled liquid delivery device and analyte monitor |
CA2205444A1 (en) | 1994-12-09 | 1996-06-13 | Novartis Ag | Transdermal system |
US5554135A (en) | 1995-02-17 | 1996-09-10 | Menyhay; Steve Z. | Sterile medical injection port and cover method and apparatus |
AU5869796A (en) | 1995-05-22 | 1996-12-11 | Ned A. Godshall | Micromechanical patch for enhancing the delivery of compound s through the skin |
WO1996037155A1 (en) | 1995-05-22 | 1996-11-28 | Silicon Microdevices, Inc. | Micromechanical device and method for enhancing delivery of compounds through the skin |
ZA9610374B (en) | 1995-12-11 | 1997-06-23 | Elan Med Tech | Cartridge-based drug delivery device |
US5801057A (en) | 1996-03-22 | 1998-09-01 | Smart; Wilson H. | Microsampling device and method of construction |
US5741224A (en) | 1996-04-16 | 1998-04-21 | Implemed, Inc. | Iontophoretic material |
FR2749172B1 (fr) * | 1996-05-31 | 1998-11-06 | Multipropulseurs | Seringue hypodermique |
JP2000511809A (ja) * | 1996-06-10 | 2000-09-12 | エラン コーポレーション ピーエルシー | 流体の皮下送給のためのニードル |
WO1998011937A1 (en) | 1996-09-17 | 1998-03-26 | Deka Products Limited Partnership | System for delivery of drugs by transport |
GB2321014A (en) * | 1997-01-14 | 1998-07-15 | Nigel John Middleton | Hypodermic needle with retractable needle guard |
US5871158A (en) | 1997-01-27 | 1999-02-16 | The University Of Utah Research Foundation | Methods for preparing devices having metallic hollow microchannels on planar substrate surfaces |
DE19717253A1 (de) * | 1997-04-24 | 1998-10-29 | Edwin Dr Med Klaus | Universal-Ideal-Nadel |
US5928207A (en) | 1997-06-30 | 1999-07-27 | The Regents Of The University Of California | Microneedle with isotropically etched tip, and method of fabricating such a device |
EP0996477B1 (en) | 1997-07-14 | 2004-01-14 | Novo Nordisk A/S | Injection member |
US6007821A (en) * | 1997-10-16 | 1999-12-28 | Fordham University | Method and compositions for the treatment of autoimmune disease using heat shock proteins |
IE970782A1 (en) | 1997-10-22 | 1999-05-05 | Elan Corp | An improved automatic syringe |
US6482176B1 (en) | 1997-11-27 | 2002-11-19 | Disetronic Licensing Ag | Method and device for controlling the introduction depth of an injection needle |
IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
US5957895A (en) | 1998-02-20 | 1999-09-28 | Becton Dickinson And Company | Low-profile automatic injection device with self-emptying reservoir |
EP1061951B1 (en) | 1998-02-25 | 2003-08-27 | THE GOVERNMENT OF THE UNITED STATES, as represented by THE SECRETARY OF THE ARMY | Use of skin penetration enhancers and barrier disruption agents to enhance the transcutaneous immune response induced by adp-ribosylating exotoxin |
US6503231B1 (en) * | 1998-06-10 | 2003-01-07 | Georgia Tech Research Corporation | Microneedle device for transport of molecules across tissue |
CA2330207C (en) | 1998-06-10 | 2005-08-30 | Georgia Tech Research Corporation | Microneedle devices and methods of manufacture and use thereof |
JP4118399B2 (ja) * | 1998-07-21 | 2008-07-16 | テルモ株式会社 | 注射針用穿刺調整具およびそれを備えた注射針組立体 |
US6428528B2 (en) | 1998-08-11 | 2002-08-06 | Antares Pharma, Inc. | Needle assisted jet injector |
EP1113832A4 (en) | 1998-09-18 | 2002-04-17 | Univ Utah Res Found | MICRO-MACHINED NEEDLES ON A SURFACE |
US6159472A (en) | 1998-11-16 | 2000-12-12 | Akzo Nobel N.V. | Intradermal Avian immunization with inactivated vaccines |
US6689103B1 (en) | 1999-05-07 | 2004-02-10 | Scimed Life System, Inc. | Injection array apparatus and method |
CA2376128C (en) | 1999-06-04 | 2009-01-06 | Georgia Tech Research Corporation | Devices and methods for enhanced microneedle penetration of biological barriers |
US6611707B1 (en) * | 1999-06-04 | 2003-08-26 | Georgia Tech Research Corporation | Microneedle drug delivery device |
US6743211B1 (en) | 1999-11-23 | 2004-06-01 | Georgia Tech Research Corporation | Devices and methods for enhanced microneedle penetration of biological barriers |
US6256533B1 (en) | 1999-06-09 | 2001-07-03 | The Procter & Gamble Company | Apparatus and method for using an intracutaneous microneedle array |
US6056176A (en) * | 1999-06-09 | 2000-05-02 | Jac Products, Inc. | Vehicle article carrier having clamping cross bar |
DE19934433A1 (de) | 1999-07-22 | 2001-01-25 | Merck Patent Gmbh | N-(Indolcarbonyl-)piperazinderivate |
US6679870B1 (en) | 1999-07-23 | 2004-01-20 | Vasca, Inc. | Methods and kits for locking and disinfecting implanted catheters |
US6319224B1 (en) * | 1999-08-20 | 2001-11-20 | Bioject Medical Technologies Inc. | Intradermal injection system for injecting DNA-based injectables into humans |
US6623457B1 (en) | 1999-09-22 | 2003-09-23 | Becton, Dickinson And Company | Method and apparatus for the transdermal administration of a substance |
US6835184B1 (en) | 1999-09-24 | 2004-12-28 | Becton, Dickinson And Company | Method and device for abrading skin |
US6331266B1 (en) | 1999-09-29 | 2001-12-18 | Becton Dickinson And Company | Process of making a molded device |
US20020156453A1 (en) | 1999-10-14 | 2002-10-24 | Pettis Ronald J. | Method and device for reducing therapeutic dosage |
US6569143B2 (en) | 1999-10-14 | 2003-05-27 | Becton, Dickinson And Company | Method of intradermally injecting substances |
US8465468B1 (en) | 2000-06-29 | 2013-06-18 | Becton, Dickinson And Company | Intradermal delivery of substances |
US6494865B1 (en) | 1999-10-14 | 2002-12-17 | Becton Dickinson And Company | Intradermal delivery device including a needle assembly |
US6569123B2 (en) | 1999-10-14 | 2003-05-27 | Becton, Dickinson And Company | Prefillable intradermal injector |
US20020095134A1 (en) | 1999-10-14 | 2002-07-18 | Pettis Ronald J. | Method for altering drug pharmacokinetics based on medical delivery platform |
WO2001039836A1 (en) | 1999-12-01 | 2001-06-07 | Natco Pharma Limited | A rapid acting freeze dired oral pharmaceutical composition for treating migraine |
GB9928578D0 (en) | 1999-12-03 | 2000-02-02 | Zeneca Ltd | Pharmaceutical formulations |
US6537242B1 (en) | 2000-06-06 | 2003-03-25 | Becton, Dickinson And Company | Method and apparatus for enhancing penetration of a member for the intradermal sampling or administration of a substance |
US6607513B1 (en) | 2000-06-08 | 2003-08-19 | Becton, Dickinson And Company | Device for withdrawing or administering a substance and method of manufacturing a device |
US20050181033A1 (en) | 2000-06-29 | 2005-08-18 | Dekker John P.Iii | Method for delivering interferons to the intradermal compartment |
US20050008683A1 (en) | 2000-06-29 | 2005-01-13 | Becton Dickinson And Company | Method for delivering interferons to the intradermal compartment |
US20040175360A1 (en) | 2000-06-29 | 2004-09-09 | Pettis Ronald J. | Method for altering drug pharmacokinetics based on medical delivery platform |
WO2002011669A2 (en) | 2000-08-07 | 2002-02-14 | Antigenics, Llc | Compositions comprising heat shock proteins or alpha(2)macroglobulin, antigenic molecules and saponins, and methods of use thereof |
US6591133B1 (en) | 2000-11-27 | 2003-07-08 | Microlin Llc | Apparatus and methods for fluid delivery using electroactive needles and implantable electrochemical delivery devices |
WO2002083232A1 (en) | 2001-04-13 | 2002-10-24 | Becton, Dickinson And Company | Methods and devices for administration of substances into the intradermal layer of skin for systemic absorption |
US20030073609A1 (en) | 2001-06-29 | 2003-04-17 | Pinkerton Thomas C. | Enhanced pharmacokinetic profile of intradermally delivered substances |
US20050010193A1 (en) | 2002-05-06 | 2005-01-13 | Laurent Philippe E. | Novel methods for administration of drugs and devices useful thereof |
US20050245594A1 (en) | 2001-06-29 | 2005-11-03 | Sutter Diane E | Dermal delivery of anti-pain agents and methods useful thereof |
DE10139410A1 (de) | 2001-08-17 | 2003-02-27 | Boehringer Ingelheim Pharma | Verwendung von BIBN4096 in Kombination mit anderen Arzneistoffen gegen Migräne für die Behandlung von Migräne |
WO2003041763A2 (en) | 2001-11-14 | 2003-05-22 | Medical Instill Technologies, Inc. | Intradermal delivery device and method |
AU2002348829A1 (en) | 2001-12-21 | 2003-07-09 | Dr. Reddy's Laboratories Ltd. | Novel compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them |
CA2474742C (en) | 2002-02-04 | 2012-01-17 | Becton, Dickinson And Company | Dermal access member |
CN1655834A (zh) | 2002-05-06 | 2005-08-17 | 贝克顿·迪金森公司 | 用于控制药代动力学的方法和装置 |
WO2004020014A2 (en) | 2002-08-30 | 2004-03-11 | Becton, Dickinson And Company | Method of controlling pharmacokinetics of immunomodulatory compounds |
BRPI0409984A (pt) | 2003-05-06 | 2006-05-09 | Becton Dickinson Co | processo para alterar a farmacocinética da insulina |
US20050096332A1 (en) | 2003-10-30 | 2005-05-05 | Boehringer Ingelheim International Gmbh | Use of tyrosine kinase inhibitors for the treatment of inflammatory processes |
US20050147525A1 (en) | 2004-01-06 | 2005-07-07 | Bousquet Gerald G. | Sanitized tubing termination method and assembly |
WO2005091922A2 (en) | 2004-03-03 | 2005-10-06 | Becton, Dickinson And Company | Methods and devices for improving delivery of a substance to skin |
US20050196380A1 (en) | 2004-03-08 | 2005-09-08 | Mikszta John A. | Method for delivering therapeutic proteins to the intradermal compartment |
US20050256182A1 (en) | 2004-05-11 | 2005-11-17 | Sutter Diane E | Formulations of anti-pain agents and methods of using the same |
-
2000
- 2000-06-29 US US09/606,909 patent/US8465468B1/en not_active Expired - Lifetime
-
2001
- 2001-06-29 US US09/897,753 patent/US20040073160A1/en not_active Abandoned
- 2001-06-29 WO PCT/US2001/020763 patent/WO2002002178A1/en active IP Right Grant
- 2001-06-29 EP EP07117551A patent/EP1880743A1/en not_active Withdrawn
- 2001-06-29 DK DK08101174.4T patent/DK1925333T3/da active
- 2001-06-29 KR KR1020027017785A patent/KR100870345B1/ko active IP Right Grant
- 2001-06-29 AU AU7585301A patent/AU7585301A/xx active Pending
- 2001-06-29 CN CN01811892A patent/CN1438905A/zh active Pending
- 2001-06-29 PT PT01948832T patent/PT1296740E/pt unknown
- 2001-06-29 DE DE60115897T patent/DE60115897T2/de not_active Expired - Lifetime
- 2001-06-29 EP EP01948832A patent/EP1296740B1/en not_active Revoked
- 2001-06-29 PT PT01953399T patent/PT1296742E/pt unknown
- 2001-06-29 CA CA002413798A patent/CA2413798C/en not_active Expired - Lifetime
- 2001-06-29 DE DE60134286T patent/DE60134286D1/de not_active Expired - Lifetime
- 2001-06-29 AU AU2001275853A patent/AU2001275853B2/en not_active Expired
- 2001-06-29 EP EP05021412A patent/EP1625870B1/en not_active Revoked
- 2001-06-29 PT PT05021412T patent/PT1625870E/pt unknown
- 2001-06-29 JP JP2002506800A patent/JP2004501725A/ja active Pending
- 2001-06-29 DK DK05021412T patent/DK1625870T3/da active
- 2001-06-29 DK DK01948832T patent/DK1296740T3/da active
- 2001-06-29 AT AT08101174T patent/ATE536906T1/de active
- 2001-06-29 KR KR1020027017786A patent/KR100897148B1/ko active IP Right Grant
- 2001-06-29 CA CA2413769A patent/CA2413769C/en not_active Expired - Lifetime
- 2001-06-29 BR BR0112313-0A patent/BR0112313A/pt not_active Application Discontinuation
- 2001-06-29 CN CN01811882A patent/CN1454104A/zh active Pending
- 2001-06-29 AT AT01948832T patent/ATE378087T1/de active
- 2001-06-29 MX MXPA03000134A patent/MXPA03000134A/es active IP Right Grant
- 2001-06-29 AU AU7026201A patent/AU7026201A/xx active Pending
- 2001-06-29 JP JP2002506799A patent/JP5614911B2/ja not_active Expired - Lifetime
- 2001-06-29 MX MXPA03000228A patent/MXPA03000228A/es active IP Right Grant
- 2001-06-29 AT AT05021412T patent/ATE396763T1/de active
- 2001-06-29 ES ES01953399T patent/ES2250437T3/es not_active Expired - Lifetime
- 2001-06-29 AU AU2001270262A patent/AU2001270262B2/en not_active Expired
- 2001-06-29 WO PCT/US2001/020782 patent/WO2002002179A1/en active IP Right Grant
- 2001-06-29 DK DK01953399T patent/DK1296742T3/da active
- 2001-06-29 ES ES01948832T patent/ES2292601T3/es not_active Expired - Lifetime
- 2001-06-29 EP EP01953399A patent/EP1296742B1/en not_active Revoked
- 2001-06-29 ES ES05021412T patent/ES2303169T3/es not_active Expired - Lifetime
- 2001-06-29 BR BR0112314-9A patent/BR0112314A/pt not_active Application Discontinuation
- 2001-06-29 EP EP08101174A patent/EP1925333B1/en not_active Revoked
- 2001-06-29 AT AT01953399T patent/ATE312644T1/de active
- 2001-06-29 ES ES08101174T patent/ES2374755T3/es not_active Expired - Lifetime
- 2001-06-29 DE DE60131401T patent/DE60131401T2/de not_active Expired - Lifetime
-
2004
- 2004-12-03 US US11/004,778 patent/US20050096630A1/en not_active Abandoned
- 2004-12-03 US US11/004,780 patent/US20050096632A1/en not_active Abandoned
- 2004-12-03 US US11/004,779 patent/US20050096631A1/en not_active Abandoned
-
2006
- 2006-03-08 CY CY20061100325T patent/CY1107458T1/el unknown
- 2006-08-15 AU AU2006203511A patent/AU2006203511A1/en not_active Abandoned
-
2008
- 2008-01-04 CY CY20081100016T patent/CY1107847T1/el unknown
- 2008-04-09 US US12/100,259 patent/US20080234656A1/en not_active Abandoned
- 2008-06-03 CY CY20081100581T patent/CY1108530T1/el unknown
-
2010
- 2010-04-06 AU AU2010201340A patent/AU2010201340B2/en not_active Expired
-
2011
- 2011-03-28 US US13/072,824 patent/US8708994B2/en not_active Expired - Fee Related
-
2013
- 2013-04-19 US US13/866,446 patent/US8998877B2/en not_active Expired - Fee Related
- 2013-04-19 US US13/866,381 patent/US9005182B2/en not_active Expired - Fee Related
- 2013-04-19 US US13/866,425 patent/US8986280B2/en not_active Expired - Fee Related
-
2014
- 2014-03-17 US US14/215,271 patent/US9242052B2/en not_active Expired - Fee Related
-
2015
- 2015-03-13 US US14/657,746 patent/US9339613B2/en not_active Expired - Fee Related
-
2016
- 2016-05-16 US US15/155,921 patent/US20160331911A1/en not_active Abandoned
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103687643A (zh) * | 2011-07-27 | 2014-03-26 | 久光制药株式会社 | 施放器 |
US9216252B2 (en) | 2011-07-27 | 2015-12-22 | Hisamitsu Pharmaceutical Co., Inc. | Applicator |
CN103687643B (zh) * | 2011-07-27 | 2016-04-20 | 久光制药株式会社 | 施放器 |
TWI561262B (zh) * | 2011-07-27 | 2016-12-11 | Hisamitsu Pharmaceutical Co | |
CN105073180A (zh) * | 2013-03-22 | 2015-11-18 | 3M创新有限公司 | 包括计数器组件的微针施用装置 |
CN105073180B (zh) * | 2013-03-22 | 2016-08-10 | 3M创新有限公司 | 包括计数器组件的微针施用装置 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1454104A (zh) | 具有刺入限制机构的物质真皮内输送针 | |
AU2001275853A1 (en) | Needle for intradermal delivery of substances having penetration limiting means | |
US20080015522A1 (en) | Dual Chamber Injector Integrated With Micro-Needles | |
WO2004024211A3 (en) | Method and device for painless injection of medication | |
CA2471493A1 (en) | A method and device for reducing therapeutic dosage | |
KR100896797B1 (ko) | 생물체 내 액상 물질 주입 장치 및 주입 방법 | |
CN214260361U (zh) | 可释放药物植入物的药物注入结构 | |
US20230007883A1 (en) | Injection pump needle mechanics | |
KR20220145500A (ko) | 마이크로구조체 주입 장치 및 주입 방법 | |
Vosseler | Transdermal chronopharmaceutical drug delivery: microneedles, intradermal infusion experiments and a delivery device |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |