CA2699271A1 - Needle-less parenteral introduction device - Google Patents
Needle-less parenteral introduction device Download PDFInfo
- Publication number
- CA2699271A1 CA2699271A1 CA2699271A CA2699271A CA2699271A1 CA 2699271 A1 CA2699271 A1 CA 2699271A1 CA 2699271 A CA2699271 A CA 2699271A CA 2699271 A CA2699271 A CA 2699271A CA 2699271 A1 CA2699271 A1 CA 2699271A1
- Authority
- CA
- Canada
- Prior art keywords
- medicament
- patient
- diameter
- needle
- skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- 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
-
- 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
- A61M37/0069—Devices for implanting pellets, e.g. markers or solid medicaments
Abstract
This invention provides a medicament having a sufficient structural strength to penetrate a patient's skin for administration of a medicament parenterally to the patient without the use of a needle. The medicament may be one having a diameter of from about 0.20 to about 0.80 mm and a length of from about 1 mm to about 5 cm. The medicament may contain at least about 10% active ingredient and may have a chosen strength of 8 or more lbs./mm2 in the longitudinal direction.
Description
NEEDLE-LESS PARENTERAL INTRODUCTION DEVICE
Field of the Invention The present invention relates to parenteral introduction devices and, in particular, to a device for intramuscular or subcutaneous administration of a pharmaceutically active composition.
Backaround of the Invention The parenteral route is preferred over oral ones in many occurrences. For example, when the drug to be administered would partially or totally degrade in the gastrointestinal tract, parenteral administration is preferred. Similarly, where there is need for rapid response iri emergency cases, parenteral administration is usually preferred over oral.
Thus, while parenteral administration is desirable in many applications, as it is currently practiced, it presents substantial drawbacks. Probably the biggest drawback is the discomfort which it causes the patient to whom the drug is being administered. Parenteral preparations generally contain a large volume of liquid in which tYie drug is suspended or dissolved. Ratios of active ingre:dient to carrier commonly run from 1:100 to 1:1000. Especially where the active ingredient is poorly soluble or difficult to suspend, or when it has to be administered at high doses, or in.both instances, a fairly large volume of liquid must be injected. The injection of the needle and the introduction of a fairly large volume: of liquid cause parenteral administration to be more or less painful, and at least disagreeable, for most people. Furthermore, depending on its nature, the solvent or the suspending agent may itself be a cause of pain.
A further disadvantage to administration of drugs in a liquid carrier is that the drugs are frequently not stable in the liquid. Therefore, the liquid and drug must be mixed substantially contemporaneously with injection. This can be of substantial disadvantage where, for example, many hundreds of people must be treated over a course of days in order to stem an epidemic.
Accordingly, it would be interesting to find a mode of administration avoiding the use both of a needle and of a liquid solution or suspension.
Parenterally administered solid compositions for use in the controlled release of a medicament are known and devices allowing direct injection of a medicament without need of a liquid are known such as, for example, trocars for implants of rods or pellets, and the device shown in European Patent Application No. 0292936 A3 for injection of a solid. However, trocars and the device of European Patent Application No. 0292936 A3 still require use of a needle.
mmary of the Invention The applicant has now discovered a comparatively inexpensive device for the ready administration of solid or semi-solid drugs by the parenteral route. The applicant's device avoids completely the need for a needle. The solid drug is injected directly through the skin of a patient, e.g., a human or animal, by a plunger which enters the skin only to the degree necessary to position the solid drug. The medicament is suitably made in the shape of the end of a toothpick, i.e., it has a pointed end which gradually tapers to a cylindrical portion. The medicament has sufficient structural strength so that it can penetrate through the skin into the subcutaneous layer when it is administered with the parenteral introduction device of the present invention.
Thus, the drug penetrates the skin and there is no need for the expense of discomfort of a needle to administer the drug parenterally. The present invention also includes an automatic device that can contain a number of doses of medicament which can be administered to a series of patients, one after the other.
Various embodiments of this invention provide a medicament adapted to be administered parenterally to a patient, said medicament having a diameter of from about 0.20 to about 0.80 mm and a length of from about 1 mm to about 5 cm, and said medicament having sufficient structural integrity to penetrate the skin of the patient.
Other embodiments of this invention provide a medicament adapted to be administered parenterally, said medicament comprising at least about 10% active ingredient, said medicament having a diameter of from about 0.20 to about 0.80 mm and a length of from about lmm to about 5 cm, and said medicament having a crush strength of 8 or more lbs./mm2 in the longitudinal direction.
Various embodiments of this invention provide a needle-less device capable of parenteral administration of a medicament, said device comprising a barrel member and a plunger, said barrel member having first and second ends and a bore for receipt of said medicament in solid form, said bore extending from said first end to said second end of said barrel, said plunger comprising an elongated rod of substantially the same outside diameter as the inside diameter of said bore, said rod being inserted into the bore at said second end of said barrel, - 3a -said plunger being capable of movement in said bore to push said medicament out said first end of the barrel member, through the skin of a patient when said barrel member is pressed against the skin of the patient and when the medicament is of sufficient structural strength to penetrate the skin of the patient.
Other embodiments of this invention provide a needle-less device capable of parenteral administration of a medicament, said device comprising a barrel member and a gas supply mechanism, said barrel member having first and second ends and a bore for receipt of said medicament in solid form, said bore extending from said first end to said second end of said barrel member, said gas supply mechanism comprising a reservoir, a gas supply valve, a regulator, and an operating button, said operating button being depressible to allow gas to flow from said reservoir through said valve and through said regulator and into said barrel member, said gas being capable of moving said medicament in said bore to push said medicament out said first end of the barrel member and through the skin of a patient when said barrel member is pressed against the skin of the patient and said button is depressed and when the medicament is of sufficient structural strength to penetrate the skin of the patient.
Other embodiments of this invention provide use of a medicament having a sufficient structural strength to penetrate a patient's skin for administration of a medicament parenterally to the patient without the use of a needle. The medicament may be a medicament of this invention as defined above.
Other embodiments of this invention provide the use of a device of this invention for parenteral administration of a medicament to a patient.
3b -Other features and advantages of the invention will be apparent from the drawings, detailed description, and from the claims.
Brief Description of the Drawings Fig. 1 is an exploded view of the parenteral introduction device according to the present invention;
Fig. 2 shows the parenteral introduction device of the present invention in its retracted form;
Fig. 3 shows the device of the present invention with a medicament having been parenterally introduced into a patient;
Fig. 4 shows the device of the invention with an automatic system where the plunger is replaced by a means for delivering pressurized gas; and Fig. 5 shows an alternative embodiment of the automatic device for administering seriatim shots to a number of individuals.
Detailed Description Referring first to Fig. 1, which is an exploded view of the parenteral introduction device of the present invention, there are three essential elements, namely a main barrel 10, a sleeve member 12, and a plunger member 14. The main barrel 10 has central bore 16 which extends from one end 22 to the other end 20 of the main barrel 10. A medicament 18 (see Fig. 2) is carried in this central bore 16. The main barrel 10 includes protruding ring members 24 and 26 which act as stops as will be hereinafter discussed. The sleeve member 12 is open at both its top 28 and bottom 30 ends. The sleeve member 12 includes shoulders 32 and 34 to limit travel of the sleeve as hereinafter discussed. Plunger member 14 includes a plunger rod 36 and an end cap 38. The end cap 38 has a circular plate member 40 and a toroidally shaped flange 42. The plunger rod 36 has an external diameter at least a portion of which is substantially the same as, or slightly smaller than, the internal diameter of the bore 16.
Fig. 2 shows the parenteral introduction device of Fig. 1 in assembled condition and in a condition suitable for transport and storage. Plunger member 14 is press fit onto the end 28 of sleeve 12. Sleeve 12 has been forced over main barrel 10 so that shoulder 32 has passed over ring member 24 and has come to rest against ring member 26. The sleeve member is in sliding engagement with the exterior surface of the main barrel 10.
Abutment of shoulder 32 with ring member 26 restrains the relative position of the sleeve 12 and the main barrel 10 so that the plunger 14 does not inadvertently dislodge the medicament 18 and push it through the said one end 22 of the main barrel 10. Ring member 24 prevents the unintentional separation of sleeve 12 from main barrel 10 since it will engage shoulder 32 before the sleeve 12 and the main barrel 10 are separated.=
A seal 44 of biologically compatible material, such as cellulose or gelatin, may be applied to the end 22 of the main barrel 10 in order to maintain the sterility of the medicament 18 until the time it is administered. Alternatively, or additionally, the entire - ~ -mechanism can be stored in a sterile environment such as a foil or ce:llophane pack (not shown).
Turning now to Fig. 3, there is shown the device in use. The said one end 22 of the main barrel 10 has been placed against the skin 48 of the patient to be treated, in such a way as to apply a tension on the zone where the me:dicament is to be injected. The plunger 14 and the sleeve 12, which travel together, have been urged down the main barrel 10 by applying pressure on the end lo cap 38 of plunger 14 until shoulder 34 comes into contact with the ring member 24. The plunger rod 36 has traversed the length of the bore 16 of the main barrel 10 and has pushed the medicament 18 through the skin 48 of the patient and into the subcutaneous layer 46. Shoulder 34 of sleeve 12 in combination with ring member 24 of main barrel 10 has limited the extent of travel of the plunger rod 36 in the main barrel 10. It is preferred that the rod 36 of plunger member 14 stop no more than 2 mm below ttie: said one end 22 of the main barrel 10 and it is most pref`erred that the plunger member not extend at all beyond the said one end 22 of the main barrel 10.
In Fig. 4, there is shown an alternative embodiment of the present invention. In the alternative embodiment, the plunger 14 is replaced by a means for providing gas pressure from a reservoir 52 and through a valve 54. The medicament 18 travels through barrel 56 under pressure of the gas. Barrel 56 can be replaced for each new irijection. When an injection is to be made, button 58 iss depressed. This allows pressure to flow from reservoir 52 through valve 54 and regulator 60. The gas then forces the medicament 18 through the barrel 56 and into the: patient (not shown). In the automatic device, this force is always the same because the amount of pressure exerted on the medicament is controlled by the regulator 60. Thus, the force of the injection is independent of any force applied by the operator.
In Fig. 5, there is disclosed an alternative embodiment of the automatic injector of Fig. 4. In this alternate embodiment, means are provided for injection of a plurality of doses to successive individuals using only a single injection device. This embodiment is illustrated in Fig. 5 where there is a magazine 62 which has a plurality of bores 64 with a medicament 18 fitted into each bore 64. As in the device of Fig. 4, gas pressure forces one of the medicaments 18 into a patient when button 58 is depressed. After delivery of the first medicament, the magazine 62 is moved to the left so that the next adjacent bore 64 and its associated medicament 18 are positioned above the barrel 56. The button 58 can be depressed to create a new gas pressure and to inject this next medicament 18 into the next patient, and thereafter, the rest of the medicaments 18 can similarly be administered seriatim to a series of individuals.
Movement of the magazine can be effected manually or can be done automatically in a known manner.
All of the components of the device may suitably be made of plastic material, but it is preferred that the automatic device be made of metal, notably stainless steel. For the manual device, the plunger 36 can be made of metal, but it can also be made of plastic if its cross-section is increased sufficiently. Even where the plunger 36 is made of steel, it may be less expensive to make than the usual syringe since=the device of the present invention does not require a stainless steel needle, the making of which requires quite a bit of precision. The main barrel 10 is preferably made with a nose cone shape at end 22. The main barrel can be made as a single piece, or, alternatively, the space between the outside wall 50 of the main barrel and wall of the central bore 16 can be hollow. The sleeve 12 is preferably made of transparent material so that the plunger rod 36 can be viewed therethrough, thus providing visual assurance that it is in its operative position.
The medicament 18 is preferably made of the shape of one end of a toothpick so that it can easily penetrate the skin and enter the subcutaneous layer. As is well known, one end of a toothpick has a point which tapers back to a cylindrical portion. The medicament is referred to as solid; however, it may be either solid or semi-solid so long as it has sufficient structural integrity to penetrate the skin without breaking apart.
It has beeri found that a medicament having a crush strength of at least about 8 killipoise in the longitudinal direction is sufficiently strong, and lesser crush strengths are also usable, especially for administratiLon to children, who have more tender skin than adultsõ
The amount of carrier in the medicament 18 depends on the drug and on the desired mode of action. As a general rule, the amount of active ingredient in the medicament is at least about 50%. With suitable medicaments which will have sufficient structural strength, the amount of medicament in the present invention can be up to 100%. The medicament may be prepared by conventional techniques such as compression, thermofusion, or extrusion. Compression suitably consists of a tabletting process in which a toothpick-shaped microtablet is formed. Thermofusion suitably consists of mixing and melting of the active ingredients and a carrier, if desired. The melted product is then molded into the toothpick-shaped medicament. Extrusion suitably consists of mixing the active ingredients and carrier, if desired, with a liquid to form a semisolid paste. The paste is then forced through a small diameter opening to form a rod. The needle-like tip can be formed prior to or after drying of the semisolid rods.
The size of the medicament 18 may be up to 2 mm in diameter but is preferably from about 0.2 to 0.8 mm, and most preferably from about 0.25 to 0.5 mm,-in diameter for the cylindrical portion of the medicament, and about 1 mm to about 3 cm in length. The size will depend, of course, on the dose to be administered and the level of active ingredient present as compared to the amount of carrier.
The inside diameter of the bore 16 is preferably about 5-10% larger than the diameter of the medicament 18. This helps to ensure that the medicament does not get "hung up" or striated by minor imperfections, such as burrs, which may be introduced into the bore 16 during manufacture. At the same time, the diameter is limited to cause frictional engagement so that the medicament is less likely to be inadvertently dislodged from the bore prior to activation of the device. An oil can be added to the bore to increase the tendency of the medicament to remain in the bore; an oil will also assist in penetration through the skin.
The diameter of the medicament is not at all arbitrary; it has been found that the introduction of a pin with a diameter of about 2 mm or less is substantially painless. Such is not the case for larger diameters, and larger diameter medicaments may general only be administered via a trocar.
The active ingredient can be a peptide or a protein. Examples of such peptides include growth hormone releasing peptide (GHRP), luteinizing hormone-releasing hormone (LHRH), somatostatin, bombesin, gastrin releasing peptide (GRP), calcitonin, bradykinin, galanin, melanocyte stimulating hormone (MSH), growth hormone releasing factor (GRF), amylin, tachykinins, secretin, parathyroid hormone (PTH), enkephalin, endothelin, calcitonin g-ene releasing peptide (CGRP), neuromedins, parathyroid hormone related protein (PTHrP), glucagon, neurotensin, adrenocorticotrophic hormone (ACTH), peptide YY (PYY), glucagon releasing peptide (GLP), factor VIII, vasoactive intestinal peptide (VIP), pituitary adenylated cyclase activating peptide (PACAP), motilin, substance P, neuropeptide: Y (NPY), TSH, and analogs and fragments thereof. Other active ingredients include insulin, adrenaline, xylocaine, morphine, a glucocorticoid (e.g., dexamethasone), atropine, a cytostatic compound, estrogen, androgen, interleukins, digitoxin, biotin, testosterone, heparin, cyclosporin, penicillin, vitamins, antiplatelet: activating factor agents (e.g., ginkgolides), or diazepam.
In order to provide instant delivery of the active ingredient, the carrier should be water soluble.
Examples of water soluble carriers include hyaluronic acid, cellulose, e.g., hydroxypropylmethyl cellulose (HPMC), carboxymethyl cellulose (CMC), and hydroxyethyl cellulose (HEC), polyalcohols, e.g., mannitol, sugars, e.g., dextrose, mannose, and glucose, gelatin, polyvinylpyrrolidone, and starches. The carrier can also be water insoluble, but biodegradable to provide sustained delivery. Examples of suitable carriers include water insoluble polyesters of L-lactic acid, D-lactic acid, DL-lactic acid, L-lactide, D-lactide, DL-lactide, glycolide, glycolic acid, capralactone, and any optically active isomers, racemates, or copolymers thereof.
The following are illustrative examples of the parenteral Etdministration of drugs in solid form as compared to the conventional liquid form, and are intended to show that the two means of administration have similar pharmaceutical efficacy.
A test was conducted with Insulin Human Recombinant (IHR) and Insulin Bovine Pancreas (IBP). IHR
is pure water soluble insulin; IBP is zinc insulin, water insoluble and prepared usually using 16% glycerol. IHR
and IBP represent about 26 Insulin Units (IU) per mg.
Different doses of insulin were compared with a conventional injectable formulation. In an in vivo test of hypoglycemic effect on rats, all these formulations were found as effective in terms of intensity and rapidity of action.
Insulin can be delivered as a dry solid and acts exactly like the usual parenteral formulation for bolus injection. The quantities needed with the device of the present invention are small enough to be administered in solid form as a 2 mm long cylinder with a 0.45 mm diameter. Patients can readily perform virtually painless introduction of solid insulin with the device of the present invention. This form of insulin is also stable for a longer time at room temperature and less expensive than the usual liquid form.
A formulation of a somatostatin analogue, D-Nal-cyclo [Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH2 was made into injectable tablets by associating the dry material with gelatin and polyvinylpyrrolidone (PVP, 5-10%). The tablets were injected and compared to conventional solutions in terms of pharmacokinetic profiles. The methods gave substantially the same pharmacological results.
A synthetic anti-PAF, 4,7,8,10-tetrahydro-l-methyl-6-(2-chlorphenyl)-9-(4-methoxyphenyl-thiocarbamoyl)-pyrido-[4',3'-4,5] thieno [3,2-f]-1,2,4-triazolo [4,5-a] 1,4-diazepine, and a natural anti-PAF, ginkgolide B., were compared to conventional administration. The synthetic anti-PAF cannot conventionally be used parenterally because of its insolubility. Nevertheless, a very good correlation between pharmacological effect and blood concentration has been observed. Ginkgolide B is slightly soluble.
For the same dose of product in solution form (pH 8.75), the effect was the same after initial injection but lasted only 2 hours with the solution whereas the effect lo lasted 24 hours with the solid dry formulation.
A prolonged formulation of decapeptyl (1 month) was made by a molding process with a molding machine into a shape of 0.8 mm diameter and=some cm long..
Polylactidecoglycolide (PLGA, 80%) was used. The pharmacokinetically controlled delivery was equivalent to that of an implant or microspheres and the solid form was perfectly injectable subcutaneously or intravenously when the device was used in different species (rabbit, dog, rat, and pig).
Other Embodiments It will be understood that the claims are intended to cover all. changes and modifications of the preferred embodiments of the invention herein chosen for the purpose of illustration which do not constitute a departure from the spirit and scope of the invention.
Field of the Invention The present invention relates to parenteral introduction devices and, in particular, to a device for intramuscular or subcutaneous administration of a pharmaceutically active composition.
Backaround of the Invention The parenteral route is preferred over oral ones in many occurrences. For example, when the drug to be administered would partially or totally degrade in the gastrointestinal tract, parenteral administration is preferred. Similarly, where there is need for rapid response iri emergency cases, parenteral administration is usually preferred over oral.
Thus, while parenteral administration is desirable in many applications, as it is currently practiced, it presents substantial drawbacks. Probably the biggest drawback is the discomfort which it causes the patient to whom the drug is being administered. Parenteral preparations generally contain a large volume of liquid in which tYie drug is suspended or dissolved. Ratios of active ingre:dient to carrier commonly run from 1:100 to 1:1000. Especially where the active ingredient is poorly soluble or difficult to suspend, or when it has to be administered at high doses, or in.both instances, a fairly large volume of liquid must be injected. The injection of the needle and the introduction of a fairly large volume: of liquid cause parenteral administration to be more or less painful, and at least disagreeable, for most people. Furthermore, depending on its nature, the solvent or the suspending agent may itself be a cause of pain.
A further disadvantage to administration of drugs in a liquid carrier is that the drugs are frequently not stable in the liquid. Therefore, the liquid and drug must be mixed substantially contemporaneously with injection. This can be of substantial disadvantage where, for example, many hundreds of people must be treated over a course of days in order to stem an epidemic.
Accordingly, it would be interesting to find a mode of administration avoiding the use both of a needle and of a liquid solution or suspension.
Parenterally administered solid compositions for use in the controlled release of a medicament are known and devices allowing direct injection of a medicament without need of a liquid are known such as, for example, trocars for implants of rods or pellets, and the device shown in European Patent Application No. 0292936 A3 for injection of a solid. However, trocars and the device of European Patent Application No. 0292936 A3 still require use of a needle.
mmary of the Invention The applicant has now discovered a comparatively inexpensive device for the ready administration of solid or semi-solid drugs by the parenteral route. The applicant's device avoids completely the need for a needle. The solid drug is injected directly through the skin of a patient, e.g., a human or animal, by a plunger which enters the skin only to the degree necessary to position the solid drug. The medicament is suitably made in the shape of the end of a toothpick, i.e., it has a pointed end which gradually tapers to a cylindrical portion. The medicament has sufficient structural strength so that it can penetrate through the skin into the subcutaneous layer when it is administered with the parenteral introduction device of the present invention.
Thus, the drug penetrates the skin and there is no need for the expense of discomfort of a needle to administer the drug parenterally. The present invention also includes an automatic device that can contain a number of doses of medicament which can be administered to a series of patients, one after the other.
Various embodiments of this invention provide a medicament adapted to be administered parenterally to a patient, said medicament having a diameter of from about 0.20 to about 0.80 mm and a length of from about 1 mm to about 5 cm, and said medicament having sufficient structural integrity to penetrate the skin of the patient.
Other embodiments of this invention provide a medicament adapted to be administered parenterally, said medicament comprising at least about 10% active ingredient, said medicament having a diameter of from about 0.20 to about 0.80 mm and a length of from about lmm to about 5 cm, and said medicament having a crush strength of 8 or more lbs./mm2 in the longitudinal direction.
Various embodiments of this invention provide a needle-less device capable of parenteral administration of a medicament, said device comprising a barrel member and a plunger, said barrel member having first and second ends and a bore for receipt of said medicament in solid form, said bore extending from said first end to said second end of said barrel, said plunger comprising an elongated rod of substantially the same outside diameter as the inside diameter of said bore, said rod being inserted into the bore at said second end of said barrel, - 3a -said plunger being capable of movement in said bore to push said medicament out said first end of the barrel member, through the skin of a patient when said barrel member is pressed against the skin of the patient and when the medicament is of sufficient structural strength to penetrate the skin of the patient.
Other embodiments of this invention provide a needle-less device capable of parenteral administration of a medicament, said device comprising a barrel member and a gas supply mechanism, said barrel member having first and second ends and a bore for receipt of said medicament in solid form, said bore extending from said first end to said second end of said barrel member, said gas supply mechanism comprising a reservoir, a gas supply valve, a regulator, and an operating button, said operating button being depressible to allow gas to flow from said reservoir through said valve and through said regulator and into said barrel member, said gas being capable of moving said medicament in said bore to push said medicament out said first end of the barrel member and through the skin of a patient when said barrel member is pressed against the skin of the patient and said button is depressed and when the medicament is of sufficient structural strength to penetrate the skin of the patient.
Other embodiments of this invention provide use of a medicament having a sufficient structural strength to penetrate a patient's skin for administration of a medicament parenterally to the patient without the use of a needle. The medicament may be a medicament of this invention as defined above.
Other embodiments of this invention provide the use of a device of this invention for parenteral administration of a medicament to a patient.
3b -Other features and advantages of the invention will be apparent from the drawings, detailed description, and from the claims.
Brief Description of the Drawings Fig. 1 is an exploded view of the parenteral introduction device according to the present invention;
Fig. 2 shows the parenteral introduction device of the present invention in its retracted form;
Fig. 3 shows the device of the present invention with a medicament having been parenterally introduced into a patient;
Fig. 4 shows the device of the invention with an automatic system where the plunger is replaced by a means for delivering pressurized gas; and Fig. 5 shows an alternative embodiment of the automatic device for administering seriatim shots to a number of individuals.
Detailed Description Referring first to Fig. 1, which is an exploded view of the parenteral introduction device of the present invention, there are three essential elements, namely a main barrel 10, a sleeve member 12, and a plunger member 14. The main barrel 10 has central bore 16 which extends from one end 22 to the other end 20 of the main barrel 10. A medicament 18 (see Fig. 2) is carried in this central bore 16. The main barrel 10 includes protruding ring members 24 and 26 which act as stops as will be hereinafter discussed. The sleeve member 12 is open at both its top 28 and bottom 30 ends. The sleeve member 12 includes shoulders 32 and 34 to limit travel of the sleeve as hereinafter discussed. Plunger member 14 includes a plunger rod 36 and an end cap 38. The end cap 38 has a circular plate member 40 and a toroidally shaped flange 42. The plunger rod 36 has an external diameter at least a portion of which is substantially the same as, or slightly smaller than, the internal diameter of the bore 16.
Fig. 2 shows the parenteral introduction device of Fig. 1 in assembled condition and in a condition suitable for transport and storage. Plunger member 14 is press fit onto the end 28 of sleeve 12. Sleeve 12 has been forced over main barrel 10 so that shoulder 32 has passed over ring member 24 and has come to rest against ring member 26. The sleeve member is in sliding engagement with the exterior surface of the main barrel 10.
Abutment of shoulder 32 with ring member 26 restrains the relative position of the sleeve 12 and the main barrel 10 so that the plunger 14 does not inadvertently dislodge the medicament 18 and push it through the said one end 22 of the main barrel 10. Ring member 24 prevents the unintentional separation of sleeve 12 from main barrel 10 since it will engage shoulder 32 before the sleeve 12 and the main barrel 10 are separated.=
A seal 44 of biologically compatible material, such as cellulose or gelatin, may be applied to the end 22 of the main barrel 10 in order to maintain the sterility of the medicament 18 until the time it is administered. Alternatively, or additionally, the entire - ~ -mechanism can be stored in a sterile environment such as a foil or ce:llophane pack (not shown).
Turning now to Fig. 3, there is shown the device in use. The said one end 22 of the main barrel 10 has been placed against the skin 48 of the patient to be treated, in such a way as to apply a tension on the zone where the me:dicament is to be injected. The plunger 14 and the sleeve 12, which travel together, have been urged down the main barrel 10 by applying pressure on the end lo cap 38 of plunger 14 until shoulder 34 comes into contact with the ring member 24. The plunger rod 36 has traversed the length of the bore 16 of the main barrel 10 and has pushed the medicament 18 through the skin 48 of the patient and into the subcutaneous layer 46. Shoulder 34 of sleeve 12 in combination with ring member 24 of main barrel 10 has limited the extent of travel of the plunger rod 36 in the main barrel 10. It is preferred that the rod 36 of plunger member 14 stop no more than 2 mm below ttie: said one end 22 of the main barrel 10 and it is most pref`erred that the plunger member not extend at all beyond the said one end 22 of the main barrel 10.
In Fig. 4, there is shown an alternative embodiment of the present invention. In the alternative embodiment, the plunger 14 is replaced by a means for providing gas pressure from a reservoir 52 and through a valve 54. The medicament 18 travels through barrel 56 under pressure of the gas. Barrel 56 can be replaced for each new irijection. When an injection is to be made, button 58 iss depressed. This allows pressure to flow from reservoir 52 through valve 54 and regulator 60. The gas then forces the medicament 18 through the barrel 56 and into the: patient (not shown). In the automatic device, this force is always the same because the amount of pressure exerted on the medicament is controlled by the regulator 60. Thus, the force of the injection is independent of any force applied by the operator.
In Fig. 5, there is disclosed an alternative embodiment of the automatic injector of Fig. 4. In this alternate embodiment, means are provided for injection of a plurality of doses to successive individuals using only a single injection device. This embodiment is illustrated in Fig. 5 where there is a magazine 62 which has a plurality of bores 64 with a medicament 18 fitted into each bore 64. As in the device of Fig. 4, gas pressure forces one of the medicaments 18 into a patient when button 58 is depressed. After delivery of the first medicament, the magazine 62 is moved to the left so that the next adjacent bore 64 and its associated medicament 18 are positioned above the barrel 56. The button 58 can be depressed to create a new gas pressure and to inject this next medicament 18 into the next patient, and thereafter, the rest of the medicaments 18 can similarly be administered seriatim to a series of individuals.
Movement of the magazine can be effected manually or can be done automatically in a known manner.
All of the components of the device may suitably be made of plastic material, but it is preferred that the automatic device be made of metal, notably stainless steel. For the manual device, the plunger 36 can be made of metal, but it can also be made of plastic if its cross-section is increased sufficiently. Even where the plunger 36 is made of steel, it may be less expensive to make than the usual syringe since=the device of the present invention does not require a stainless steel needle, the making of which requires quite a bit of precision. The main barrel 10 is preferably made with a nose cone shape at end 22. The main barrel can be made as a single piece, or, alternatively, the space between the outside wall 50 of the main barrel and wall of the central bore 16 can be hollow. The sleeve 12 is preferably made of transparent material so that the plunger rod 36 can be viewed therethrough, thus providing visual assurance that it is in its operative position.
The medicament 18 is preferably made of the shape of one end of a toothpick so that it can easily penetrate the skin and enter the subcutaneous layer. As is well known, one end of a toothpick has a point which tapers back to a cylindrical portion. The medicament is referred to as solid; however, it may be either solid or semi-solid so long as it has sufficient structural integrity to penetrate the skin without breaking apart.
It has beeri found that a medicament having a crush strength of at least about 8 killipoise in the longitudinal direction is sufficiently strong, and lesser crush strengths are also usable, especially for administratiLon to children, who have more tender skin than adultsõ
The amount of carrier in the medicament 18 depends on the drug and on the desired mode of action. As a general rule, the amount of active ingredient in the medicament is at least about 50%. With suitable medicaments which will have sufficient structural strength, the amount of medicament in the present invention can be up to 100%. The medicament may be prepared by conventional techniques such as compression, thermofusion, or extrusion. Compression suitably consists of a tabletting process in which a toothpick-shaped microtablet is formed. Thermofusion suitably consists of mixing and melting of the active ingredients and a carrier, if desired. The melted product is then molded into the toothpick-shaped medicament. Extrusion suitably consists of mixing the active ingredients and carrier, if desired, with a liquid to form a semisolid paste. The paste is then forced through a small diameter opening to form a rod. The needle-like tip can be formed prior to or after drying of the semisolid rods.
The size of the medicament 18 may be up to 2 mm in diameter but is preferably from about 0.2 to 0.8 mm, and most preferably from about 0.25 to 0.5 mm,-in diameter for the cylindrical portion of the medicament, and about 1 mm to about 3 cm in length. The size will depend, of course, on the dose to be administered and the level of active ingredient present as compared to the amount of carrier.
The inside diameter of the bore 16 is preferably about 5-10% larger than the diameter of the medicament 18. This helps to ensure that the medicament does not get "hung up" or striated by minor imperfections, such as burrs, which may be introduced into the bore 16 during manufacture. At the same time, the diameter is limited to cause frictional engagement so that the medicament is less likely to be inadvertently dislodged from the bore prior to activation of the device. An oil can be added to the bore to increase the tendency of the medicament to remain in the bore; an oil will also assist in penetration through the skin.
The diameter of the medicament is not at all arbitrary; it has been found that the introduction of a pin with a diameter of about 2 mm or less is substantially painless. Such is not the case for larger diameters, and larger diameter medicaments may general only be administered via a trocar.
The active ingredient can be a peptide or a protein. Examples of such peptides include growth hormone releasing peptide (GHRP), luteinizing hormone-releasing hormone (LHRH), somatostatin, bombesin, gastrin releasing peptide (GRP), calcitonin, bradykinin, galanin, melanocyte stimulating hormone (MSH), growth hormone releasing factor (GRF), amylin, tachykinins, secretin, parathyroid hormone (PTH), enkephalin, endothelin, calcitonin g-ene releasing peptide (CGRP), neuromedins, parathyroid hormone related protein (PTHrP), glucagon, neurotensin, adrenocorticotrophic hormone (ACTH), peptide YY (PYY), glucagon releasing peptide (GLP), factor VIII, vasoactive intestinal peptide (VIP), pituitary adenylated cyclase activating peptide (PACAP), motilin, substance P, neuropeptide: Y (NPY), TSH, and analogs and fragments thereof. Other active ingredients include insulin, adrenaline, xylocaine, morphine, a glucocorticoid (e.g., dexamethasone), atropine, a cytostatic compound, estrogen, androgen, interleukins, digitoxin, biotin, testosterone, heparin, cyclosporin, penicillin, vitamins, antiplatelet: activating factor agents (e.g., ginkgolides), or diazepam.
In order to provide instant delivery of the active ingredient, the carrier should be water soluble.
Examples of water soluble carriers include hyaluronic acid, cellulose, e.g., hydroxypropylmethyl cellulose (HPMC), carboxymethyl cellulose (CMC), and hydroxyethyl cellulose (HEC), polyalcohols, e.g., mannitol, sugars, e.g., dextrose, mannose, and glucose, gelatin, polyvinylpyrrolidone, and starches. The carrier can also be water insoluble, but biodegradable to provide sustained delivery. Examples of suitable carriers include water insoluble polyesters of L-lactic acid, D-lactic acid, DL-lactic acid, L-lactide, D-lactide, DL-lactide, glycolide, glycolic acid, capralactone, and any optically active isomers, racemates, or copolymers thereof.
The following are illustrative examples of the parenteral Etdministration of drugs in solid form as compared to the conventional liquid form, and are intended to show that the two means of administration have similar pharmaceutical efficacy.
A test was conducted with Insulin Human Recombinant (IHR) and Insulin Bovine Pancreas (IBP). IHR
is pure water soluble insulin; IBP is zinc insulin, water insoluble and prepared usually using 16% glycerol. IHR
and IBP represent about 26 Insulin Units (IU) per mg.
Different doses of insulin were compared with a conventional injectable formulation. In an in vivo test of hypoglycemic effect on rats, all these formulations were found as effective in terms of intensity and rapidity of action.
Insulin can be delivered as a dry solid and acts exactly like the usual parenteral formulation for bolus injection. The quantities needed with the device of the present invention are small enough to be administered in solid form as a 2 mm long cylinder with a 0.45 mm diameter. Patients can readily perform virtually painless introduction of solid insulin with the device of the present invention. This form of insulin is also stable for a longer time at room temperature and less expensive than the usual liquid form.
A formulation of a somatostatin analogue, D-Nal-cyclo [Cys-Tyr-D-Trp-Lys-Val-Cys]-Thr-NH2 was made into injectable tablets by associating the dry material with gelatin and polyvinylpyrrolidone (PVP, 5-10%). The tablets were injected and compared to conventional solutions in terms of pharmacokinetic profiles. The methods gave substantially the same pharmacological results.
A synthetic anti-PAF, 4,7,8,10-tetrahydro-l-methyl-6-(2-chlorphenyl)-9-(4-methoxyphenyl-thiocarbamoyl)-pyrido-[4',3'-4,5] thieno [3,2-f]-1,2,4-triazolo [4,5-a] 1,4-diazepine, and a natural anti-PAF, ginkgolide B., were compared to conventional administration. The synthetic anti-PAF cannot conventionally be used parenterally because of its insolubility. Nevertheless, a very good correlation between pharmacological effect and blood concentration has been observed. Ginkgolide B is slightly soluble.
For the same dose of product in solution form (pH 8.75), the effect was the same after initial injection but lasted only 2 hours with the solution whereas the effect lo lasted 24 hours with the solid dry formulation.
A prolonged formulation of decapeptyl (1 month) was made by a molding process with a molding machine into a shape of 0.8 mm diameter and=some cm long..
Polylactidecoglycolide (PLGA, 80%) was used. The pharmacokinetically controlled delivery was equivalent to that of an implant or microspheres and the solid form was perfectly injectable subcutaneously or intravenously when the device was used in different species (rabbit, dog, rat, and pig).
Other Embodiments It will be understood that the claims are intended to cover all. changes and modifications of the preferred embodiments of the invention herein chosen for the purpose of illustration which do not constitute a departure from the spirit and scope of the invention.
Claims (9)
1. A medicament adapted to be administered parenterally to a patient, said medicament having a diameter of from about 0.20 to about 0.80 mm and a length of from about 1 mm to about 5 cm, and said medicament having sufficient structural integrity to penetrate skin of the patient.
2. The medicament of claim 1, wherein the medicament has a crush strength of 8 or more lbs/mm2 in longitudinal direction.
3. A medicament adapted to be administered parenterally, said medicament comprising at least about 10%
active ingredient, said medicament having a diameter of from about 0.20 to about 0.80 mm and a length of from about 1mm to about 5 cm, and said medicament having a crush strength of 8 or more lbs/mm2 in longitudinal direction.
active ingredient, said medicament having a diameter of from about 0.20 to about 0.80 mm and a length of from about 1mm to about 5 cm, and said medicament having a crush strength of 8 or more lbs/mm2 in longitudinal direction.
4. The medicament of claim 1, 2 or 3, wherein the diameter of said medicament is from about 0.25 to about 0.50 mm.
5. The medicament of any one of claims 1 to 4, wherein said medicament has the shape of a toothpick with a frustoconical point at one end thereof.
6. The medicament of any one of claims 1 to 4, having the shape of one end of a toothpick and includes a tip with a cone based on a cylindrical portion and wherein said tip is for alignment towards a site of said parenteral administration.
7. The medicament of any one of claims 1 to 6, wherein said medicament comprises substantially 100% active ingredient.
8. Use of a medicament having a sufficient structural strength to penetrate a patient's skin for administration of a medicament parenterally to the patient without the use of a needle.
9. The use of claim 8, wherein the medicament is as defined in any one of claims 1 to 7.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/304,274 US5542920A (en) | 1994-09-12 | 1994-09-12 | Needle-less parenteral introduction device |
US08/304,274 | 1994-09-12 | ||
CA2199516A CA2199516C (en) | 1994-09-12 | 1995-09-12 | Needle-less parenteral introduction device |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2199516A Division CA2199516C (en) | 1994-09-12 | 1995-09-12 | Needle-less parenteral introduction device |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2699271A1 true CA2699271A1 (en) | 1996-03-21 |
CA2699271C CA2699271C (en) | 2013-10-22 |
Family
ID=23175806
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2699271A Expired - Lifetime CA2699271C (en) | 1994-09-12 | 1995-09-12 | Needle-less parenteral introduction device |
CA2199516A Expired - Lifetime CA2199516C (en) | 1994-09-12 | 1995-09-12 | Needle-less parenteral introduction device |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2199516A Expired - Lifetime CA2199516C (en) | 1994-09-12 | 1995-09-12 | Needle-less parenteral introduction device |
Country Status (12)
Country | Link |
---|---|
US (4) | US5542920A (en) |
EP (1) | EP0782465B1 (en) |
JP (2) | JPH10505526A (en) |
KR (2) | KR100261580B1 (en) |
AT (1) | ATE173941T1 (en) |
AU (1) | AU705266B2 (en) |
BR (1) | BR9508830A (en) |
CA (2) | CA2699271C (en) |
DE (1) | DE69506428T2 (en) |
DK (1) | DK0782465T3 (en) |
ES (1) | ES2125657T3 (en) |
WO (1) | WO1996008289A1 (en) |
Families Citing this family (90)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5458596A (en) | 1994-05-06 | 1995-10-17 | Dorsal Orthopedic Corporation | Method and apparatus for controlled contraction of soft tissue |
US5595973A (en) * | 1994-09-12 | 1997-01-21 | Biomeasure Incorporated | Protection of hemopoietic cells during chemotherapy or radiotherapy |
US5542920A (en) * | 1994-09-12 | 1996-08-06 | Delab | Needle-less parenteral introduction device |
US6461353B1 (en) | 1995-02-17 | 2002-10-08 | Oratec Interventions, Inc. | Orthopedic apparatus for controlled contraction of collagen tissue |
US6283960B1 (en) | 1995-10-24 | 2001-09-04 | Oratec Interventions, Inc. | Apparatus for delivery of energy to a surgical site |
US6007570A (en) | 1996-08-13 | 1999-12-28 | Oratec Interventions, Inc. | Apparatus with functional element for performing function upon intervertebral discs |
US6122549A (en) | 1996-08-13 | 2000-09-19 | Oratec Interventions, Inc. | Apparatus for treating intervertebral discs with resistive energy |
US5823994A (en) * | 1996-03-15 | 1998-10-20 | Oratec Interventions, Inc. | Method and apparatus for soft tissue fixation |
US6832997B2 (en) | 2001-06-06 | 2004-12-21 | Oratec Interventions, Inc. | Electromagnetic energy delivery intervertebral disc treatment devices |
US6126682A (en) | 1996-08-13 | 2000-10-03 | Oratec Interventions, Inc. | Method for treating annular fissures in intervertebral discs |
WO1999047058A2 (en) | 1998-03-19 | 1999-09-23 | Oratec Interventions, Inc. | Catheter for delivery of energy to a surgical site |
US6733496B2 (en) | 2001-06-06 | 2004-05-11 | Oratec Interventions, Inc. | Intervertebral disc device employing flexible probe |
US6726685B2 (en) | 2001-06-06 | 2004-04-27 | Oratec Interventions, Inc. | Intervertebral disc device employing looped probe |
US6645203B2 (en) | 1997-02-12 | 2003-11-11 | Oratec Interventions, Inc. | Surgical instrument with off-axis electrode |
US6068628A (en) | 1996-08-20 | 2000-05-30 | Oratec Interventions, Inc. | Apparatus for treating chondromalacia |
US20020111603A1 (en) * | 1996-12-02 | 2002-08-15 | Societe De Conseils De Recherches Et D'application | Device for local administration of solid or semi-solid formulations and delayed-release formulations for proposal parental administration and preparation process |
FR2756493B1 (en) * | 1996-12-02 | 2001-04-13 | Delab | DEVICE FOR LOCAL ADMINISTRATION OF SOLID OR SEMI-SOLID FORMULATIONS |
JP2001511048A (en) | 1997-02-12 | 2001-08-07 | オーレイテック インターヴェンションズ インコーポレイテッド | Electrode for electrosurgical removal of tissue and method of manufacturing the same |
EP1006908A2 (en) | 1997-02-12 | 2000-06-14 | Oratec Interventions, Inc. | Concave probe for arthroscopic surgery |
US5954716A (en) | 1997-02-19 | 1999-09-21 | Oratec Interventions, Inc | Method for modifying the length of a ligament |
US6214001B1 (en) | 1997-09-19 | 2001-04-10 | Oratec Interventions, Inc. | Electrocauterizing tool for orthopedic shave devices |
US6007533A (en) | 1997-09-19 | 1999-12-28 | Oratec Interventions, Inc. | Electrocauterizing tip for orthopedic shave devices |
US6004320A (en) | 1997-09-19 | 1999-12-21 | Oratec Interventions, Inc. | Clip on electrocauterizing sheath for orthopedic shave devices |
US6176857B1 (en) | 1997-10-22 | 2001-01-23 | Oratec Interventions, Inc. | Method and apparatus for applying thermal energy to tissue asymmetrically |
KR100246044B1 (en) * | 1998-02-20 | 2000-03-15 | 성재갑 | Administration device |
AU3957400A (en) | 1999-04-16 | 2000-11-02 | Novo Nordisk A/S | Dry, mouldable drug formulation |
JP2002541920A (en) * | 1999-04-16 | 2002-12-10 | ノボ ノルディスク アクティーゼルスカブ | Solid medicine storage and insertion cassette |
US6485453B1 (en) | 1999-04-16 | 2002-11-26 | Novo Nordisk A/S | Cassette for storing and insertion of solid medicine |
DE60010919T2 (en) * | 1999-10-13 | 2005-06-09 | Novo Nordisk A/S | METHOD FOR THE PRODUCTION OF MEDICAL FORM BODIES |
EP1313425B1 (en) * | 2000-07-14 | 2007-03-07 | Novo Nordisk A/S | Method of moulding a pharmaceutical composition in a packaging material |
DE10110513A1 (en) * | 2001-01-29 | 2002-12-12 | Ulrich Werth | Implant and method and device for inserting the implant into living tissue |
US6695839B2 (en) | 2001-02-08 | 2004-02-24 | Oratec Interventions, Inc. | Method and apparatus for treatment of disrupted articular cartilage |
US6638276B2 (en) | 2001-06-06 | 2003-10-28 | Oratec Interventions, Inc. | Intervertebral disc device employing prebent sheath |
US7615234B2 (en) * | 2001-09-11 | 2009-11-10 | Glide Pharmaceutical Technologies Limited | Drug delivery technology |
GB2391480B (en) * | 2002-08-05 | 2007-02-28 | Caretek Medical Ltd | Drug delivery system |
GB2379390B (en) | 2001-09-11 | 2005-01-26 | Caretek Medical Ltd | A novel drug delivery technology |
US8454997B2 (en) | 2001-12-18 | 2013-06-04 | Novo Nordisk A/S | Solid dose micro implant |
US7470250B2 (en) * | 2002-03-22 | 2008-12-30 | Novo Nordisk A/S | Apparatus for automatic insertion of a solid medicine |
WO2003103751A1 (en) * | 2002-06-10 | 2003-12-18 | Akzo Nobel N.V. | Needle-less injector |
EP1534376B1 (en) * | 2002-06-25 | 2016-08-31 | Theraject, Inc. | Rapidly dissolving micro-perforator for drug delivery and other applications |
ATE419794T1 (en) * | 2002-08-01 | 2009-01-15 | Abbott Lab Vascular Entpr Ltd | INJECTION DEVICE FOR SEALING PUNCTURE WOUNDS |
US6899717B2 (en) * | 2002-09-18 | 2005-05-31 | Allergan, Inc. | Methods and apparatus for delivery of ocular implants |
US7468065B2 (en) | 2002-09-18 | 2008-12-23 | Allergan, Inc. | Apparatus for delivery of ocular implants |
KR20050047118A (en) * | 2002-09-18 | 2005-05-19 | 알러간, 인코포레이티드 | Methods and apparatus for delivery of ocular implants |
IL157981A (en) | 2003-09-17 | 2014-01-30 | Elcam Medical Agricultural Cooperative Ass Ltd | Auto-injector |
US7361182B2 (en) * | 2003-12-19 | 2008-04-22 | Lightnix, Inc. | Medical lancet |
IL160891A0 (en) | 2004-03-16 | 2004-08-31 | Auto-mix needle | |
US7815941B2 (en) | 2004-05-12 | 2010-10-19 | Baxter Healthcare S.A. | Nucleic acid microspheres, production and delivery thereof |
CN103432079A (en) | 2004-05-12 | 2013-12-11 | 巴克斯特国际公司 | Oligonucleotide-containing microspheres, their use for the manufacture of a medicament for treating diabetes type 1 |
JP4960252B2 (en) | 2004-11-22 | 2012-06-27 | インテリジェクト,インコーポレイテッド | Device, system and method for drug delivery |
US10737028B2 (en) | 2004-11-22 | 2020-08-11 | Kaleo, Inc. | Devices, systems and methods for medicament delivery |
US11590286B2 (en) | 2004-11-22 | 2023-02-28 | Kaleo, Inc. | Devices, systems and methods for medicament delivery |
US7648483B2 (en) | 2004-11-22 | 2010-01-19 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
EP1666084A1 (en) * | 2004-12-01 | 2006-06-07 | Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S) SAS | Injection device for a pharmaceutical active ingredient |
WO2006058426A1 (en) | 2004-12-01 | 2006-06-08 | Wlt Distributors Inc. | Needle-free injector |
EP1666085A1 (en) * | 2004-12-01 | 2006-06-07 | Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S) SAS | Injection device for a solid implant |
AU2006209421A1 (en) | 2005-01-31 | 2006-08-03 | Bioserentach Co., Ltd. | Transdermal absorption preparation, sheet holding transdermal absorption preparation and transdermal absorption preparation holder |
GB2422784A (en) * | 2005-02-07 | 2006-08-09 | Caretek Medical Ltd | Disposable assembly comprising a needle or stylet |
US7533490B2 (en) * | 2005-06-30 | 2009-05-19 | Innovated Agricultural Concepts, Llc | Method for creating a verified food source |
US8668676B2 (en) * | 2006-06-19 | 2014-03-11 | Allergan, Inc. | Apparatus and methods for implanting particulate ocular implants |
US9039761B2 (en) | 2006-08-04 | 2015-05-26 | Allergan, Inc. | Ocular implant delivery assemblies with distal caps |
GB2446780A (en) * | 2007-02-22 | 2008-08-27 | Glide Pharmaceutical Technolog | An elongate parenteral injection body having an injection point of angle 10 to 40 degrees. |
AU2014253541B2 (en) * | 2007-02-22 | 2016-07-28 | Glide Pharmaceutical Technologies Limited | Solid pharmaceutical and vaccine dose |
NZ583832A (en) * | 2007-09-07 | 2012-08-31 | Quadra Logic Tech Inc | Implant insertion tool with a tissue stop configuired to engage tissue |
CA2705239C (en) | 2007-11-08 | 2018-09-25 | Alimera Sciences, Inc. | Ocular implantation device |
WO2009069112A1 (en) | 2007-11-28 | 2009-06-04 | Janisys Limited | A delivery device for administering an active substance to a subject |
DE102008005938A1 (en) * | 2008-01-24 | 2009-07-30 | Arzneimittel Gmbh Apotheker Vetter & Co. Ravensburg | Pre-filled syringe for use in ophthalmology field, has piston rod with end coupled with stopper and opposite end, and aseptic secondary package e.g. cylindrical casing, with inner area provided for accommodation of syringe |
ES2551940T3 (en) * | 2008-02-18 | 2015-11-24 | Azurebio, S.L. | Devices for administering medications and vaccines in the form of injectable needles |
US8309132B2 (en) * | 2008-05-16 | 2012-11-13 | Bezwada Biomedical, Llc | Bioabsorbable polyesteramides and uses thereof |
US8545554B2 (en) * | 2009-01-16 | 2013-10-01 | Allergan, Inc. | Intraocular injector |
JP5969212B2 (en) * | 2009-02-10 | 2016-08-17 | シヴィダ・ユーエス・インコーポレイテッドPsivida Us,Inc. | Ophthalmic trocar assembly |
US10286150B2 (en) * | 2009-03-31 | 2019-05-14 | Michael Harms | Dose button for a drug delivery device and method for manufacturing a dose button |
ES2362525B8 (en) | 2009-10-08 | 2013-01-03 | Azurebio, S.L. | Medication formulation in the form of penetrating percutaneous needles. |
WO2011057031A1 (en) * | 2009-11-04 | 2011-05-12 | Triune Ip Llc | Remote manipulation apparatus and system |
US20110213317A1 (en) * | 2010-03-01 | 2011-09-01 | Chen David E-Bin | Cannula for intraocular surgery |
US9084849B2 (en) * | 2011-01-26 | 2015-07-21 | Kaleo, Inc. | Medicament delivery devices for administration of a medicament within a prefilled syringe |
US9233238B2 (en) * | 2011-02-23 | 2016-01-12 | Ams Research Corporation | Drug releasing pelvic treatment system and method |
US9522235B2 (en) | 2012-05-22 | 2016-12-20 | Kaleo, Inc. | Devices and methods for delivering medicaments from a multi-chamber container |
US10391291B2 (en) * | 2012-10-02 | 2019-08-27 | Robert F. Wallace | Implant insertion system |
JP2017528227A (en) | 2014-09-11 | 2017-09-28 | ピーシビダ ユーエス,インコーポレイテッド | Injection equipment |
CA2980004C (en) | 2015-03-24 | 2023-10-10 | Kaleo, Inc. | Devices and methods for delivering a lyophilized medicament |
WO2017004345A1 (en) | 2015-06-30 | 2017-01-05 | Kaleo, Inc. | Auto-injectors for administration of a medicament within a prefilled syringe |
GB2545880A (en) | 2015-10-20 | 2017-07-05 | Glide Pharmaceutical Tech Ltd | Solid formulation |
USD851755S1 (en) | 2015-10-22 | 2019-06-18 | Eyepoint Pharmaceuticals Us, Inc. | Ocular inserter |
JP2018039761A (en) * | 2016-09-08 | 2018-03-15 | コスメディ製薬株式会社 | Double-needles type microneedle |
CA3046228A1 (en) | 2016-12-23 | 2018-06-28 | Kaleo, Inc. | Medicament delivery device and methods for delivering drugs to infants and children |
US10888693B2 (en) | 2017-08-22 | 2021-01-12 | Warsaw Orthopedic, Inc. | Drug pellet injector needle and method |
EP3603650A1 (en) | 2018-08-01 | 2020-02-05 | Edix O Sarl | Injectable and prolonged action compositions for use in the treatment of diseases of the nail and/or to accelerate nail growth |
WO2020025683A1 (en) | 2018-08-01 | 2020-02-06 | Edix-O Sarl | Injectable prolonged-action compositions for use in the treatment of nail disease and/or for promoting nail growth |
CA3145580A1 (en) | 2019-08-09 | 2021-02-18 | Kaleo, Inc. | Devices and methods for delivery of substances within a prefilled syringe |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB191400091A (en) * | 1914-01-01 | 1914-05-07 | John Beaumont Hotham | Improved Means for Intermittently Establishing an Electric Circuit for Indicating or Recording the Level of Liquids or for other purposes. |
US2630804A (en) * | 1948-02-24 | 1953-03-10 | Ortho Pharma Corp | Single dose cavity dispenser |
GB698275A (en) * | 1950-01-16 | 1953-10-14 | Schering Ag | Improvements in surgical injection devices |
US2589388A (en) * | 1951-03-12 | 1952-03-18 | Cora H Hunter | Suppository injector |
US3072121A (en) * | 1956-07-24 | 1963-01-08 | Nat Tuberculosis Ass | Pellet injector |
US3572335A (en) * | 1969-01-10 | 1971-03-23 | Ralph R Robinson | Cervical implant method and device |
US4060083A (en) * | 1976-04-01 | 1977-11-29 | Hanson Raymond L | Pill gun |
US4326524A (en) * | 1980-09-30 | 1982-04-27 | Minnesota Mining And Manufacturing Company | Solid dose ballistic projectile |
GB2091554B (en) * | 1981-01-13 | 1984-09-12 | Mitsui Toatsu Chemicals | Rod like moulded drug |
US4697575A (en) * | 1984-11-21 | 1987-10-06 | Henry Ford Hospital | Delivery system for interstitial radiation therapy including substantially non-deflecting elongated member |
US4820267A (en) * | 1985-02-19 | 1989-04-11 | Endocon, Inc. | Cartridge injector for pellet medicaments |
US4871094A (en) * | 1986-12-31 | 1989-10-03 | Alcon Laboratories, Inc. | Means and method for dispensing substances |
US4994028A (en) * | 1987-03-18 | 1991-02-19 | Endocon, Inc. | Injector for inplanting multiple pellet medicaments |
CA1296231C (en) * | 1987-05-26 | 1992-02-25 | Keiji Fujioka | Device for administering solid preparations |
US4808166A (en) * | 1987-10-08 | 1989-02-28 | James Davidov | Anal medication applicator |
NL8901124A (en) * | 1989-05-03 | 1990-12-03 | Nedap Nv | Closed implanting instrument - accommodates sterile injection needle and implant before use |
WO1992008508A1 (en) * | 1990-11-09 | 1992-05-29 | Sy-Quest International Limited | Needleless hypodermic jet injector device |
NL9101489A (en) * | 1991-09-03 | 1993-04-01 | Texas Instruments Holland | INJECTOR FOR IMMEDIATELY IMPLANTING AN OBJECT IN A LIVING BEING. |
NL9200581A (en) * | 1992-03-30 | 1993-10-18 | Akuaba B V | IMPLANT DEVICE. |
NL9200844A (en) * | 1992-05-13 | 1993-12-01 | De Wijdeven Gijsbertus G P Van | DEVICE AND METHOD FOR INJECTING WITH A SOLID SUBSTANCE. |
US5304119A (en) * | 1993-06-24 | 1994-04-19 | Monsanto Company | Instrument for injecting implants through animal hide |
US5399162A (en) * | 1994-02-23 | 1995-03-21 | Cselle; Edward | Automatic balling gun |
US5542920A (en) * | 1994-09-12 | 1996-08-06 | Delab | Needle-less parenteral introduction device |
-
1994
- 1994-09-12 US US08/304,274 patent/US5542920A/en not_active Expired - Lifetime
-
1995
- 1995-09-12 US US08/793,955 patent/US6120786A/en not_active Expired - Lifetime
- 1995-09-12 WO PCT/IB1995/000841 patent/WO1996008289A1/en not_active Application Discontinuation
- 1995-09-12 JP JP8510048A patent/JPH10505526A/en not_active Ceased
- 1995-09-12 DK DK95932142T patent/DK0782465T3/en active
- 1995-09-12 ES ES95932142T patent/ES2125657T3/en not_active Expired - Lifetime
- 1995-09-12 BR BR9508830A patent/BR9508830A/en not_active Application Discontinuation
- 1995-09-12 AT AT95932142T patent/ATE173941T1/en active
- 1995-09-12 AU AU35315/95A patent/AU705266B2/en not_active Expired
- 1995-09-12 DE DE69506428T patent/DE69506428T2/en not_active Expired - Lifetime
- 1995-09-12 CA CA2699271A patent/CA2699271C/en not_active Expired - Lifetime
- 1995-09-12 KR KR1019970701597A patent/KR100261580B1/en not_active IP Right Cessation
- 1995-09-12 EP EP95932142A patent/EP0782465B1/en not_active Expired - Lifetime
- 1995-09-12 CA CA2199516A patent/CA2199516C/en not_active Expired - Lifetime
-
1999
- 1999-06-22 US US09/337,929 patent/US6117443A/en not_active Expired - Lifetime
-
2000
- 2000-02-11 KR KR1020000006510A patent/KR100359587B1/en not_active IP Right Cessation
-
2002
- 2002-12-13 US US10/318,935 patent/US6896893B2/en not_active Expired - Fee Related
-
2006
- 2006-07-10 JP JP2006189108A patent/JP2006320736A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
DK0782465T3 (en) | 1999-08-16 |
ES2125657T3 (en) | 1999-03-01 |
US20030082216A1 (en) | 2003-05-01 |
DE69506428T2 (en) | 1999-06-02 |
US6117443A (en) | 2000-09-12 |
US6896893B2 (en) | 2005-05-24 |
CA2699271C (en) | 2013-10-22 |
AU3531595A (en) | 1996-03-29 |
BR9508830A (en) | 1998-11-03 |
US5542920A (en) | 1996-08-06 |
EP0782465A1 (en) | 1997-07-09 |
KR100261580B1 (en) | 2000-07-15 |
EP0782465B1 (en) | 1998-12-02 |
JPH10505526A (en) | 1998-06-02 |
WO1996008289A1 (en) | 1996-03-21 |
CA2199516A1 (en) | 1996-03-21 |
ATE173941T1 (en) | 1998-12-15 |
AU705266B2 (en) | 1999-05-20 |
DE69506428D1 (en) | 1999-01-14 |
JP2006320736A (en) | 2006-11-30 |
KR100359587B1 (en) | 2002-11-07 |
CA2199516C (en) | 2010-06-08 |
US6120786A (en) | 2000-09-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2699271C (en) | Needle-less parenteral introduction device | |
US6544545B1 (en) | Needle-less parenteral introduction device | |
EP0783342B1 (en) | Safety injection device | |
EP1498150B1 (en) | Device for delivery of solid drug compositions | |
AU713066B2 (en) | Sustained release of peptides from pharmaceutical compositions | |
EP0778785B1 (en) | Methods and apparatus for the delivery of solid drug compositions | |
TWI715520B (en) | Pharmaceutical composition for a sustained release of lanreotide | |
US20180021556A1 (en) | Painless drug implanter | |
AU745055B2 (en) | Parenterally administered medicament | |
CN1163578A (en) | Needle-less parenteral introduction device | |
CN110177587A (en) | Drug delivery device and system |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
EEER | Examination request |
Effective date: 20100409 |
|
MKEX | Expiry |
Effective date: 20150914 |