JPH0566153B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a housing for injecting a specific drug or therapeutic agent (hereinafter collectively referred to as a drug) into the body. More particularly, the present invention relates to a housing adapted to a patient's body device for delivering small amounts of medication over an extended period of time.

The present invention is disclosed in U.S. Patent No. 4340048 and No.
No. 4,474,575 relates to a body-worn pump.

As described in the above-mentioned patents, there are now small and compact complete devices that can be worn inside or outside the body and deliver precisely controlled amounts of various activators over extended periods of time. There is a demand for a pump with a These devices are covered by US Patent Nos. 4320757; 4320757; 4282872;
No. 3,731,681; This represents a major advance over the typical subcutaneous medication delivered into the body via any of the following syringes. This soft drug is absorbed into the body and distributed throughout the body, although the process differs depending on each patient's physiological mechanism. Therefore, three doses separated by a long period of time, such as 24 hours or more, in highly potent activators such as insulin, interferon, or other chemotherapeutic agents.
It is now recognized that it is preferable to inject the activator at a continuous slow rate over the same period of time rather than four or more injections. Furthermore, the body's requirements for active agents such as insulin vary depending on the conditions. Throughout the day, a typical diabetic patient
Although a continuous or basal amount of insulin is required, additional insulin is required after a meal to compensate for the physiological changes caused by the meal. Therefore, it is preferred to provide a continuous infusion pump with a continuous flow pulse dosing device.

The infusion pump disclosed in the aforementioned patent is compact, reliable, and compact compared to other conventional devices.
It is a significant technological improvement as it is reliable and relatively inexpensive. In considering such devices, we have determined that the human and mechanical engineering factors of infusion pumps are
confirmed that it must be carefully considered to be acceptable to patients. These factors are a wide range of considerations.
“Patient Reaction to Long−” by Pickup etc.
term Out−patient treatment with
Continuous Subcutaneous Insulin Infusion”
Br.Med.J.Vol282, pp.766-768, March, 1981,
As discussed in , the psychological impact of wearing a pump regarding the size of the pump and the patient's interpersonal relationship generated completely opposite criticism. Other factors that must be addressed to obtain patient acceptance and approval are ease of operation, minimal adjustment for start-up and donning, ease of concealment, comfort, inexpensiveness, maintenance-free design, and attractiveness in use. Appearance, compact size and e.g. filled, empty, pump working. This is to check the status of the equipment, such as whether it is stopped or not.

The present invention provides a compact, lightweight drug that is capable of dispensing water-soluble and water-insoluble drugs at a continuous rate, continuously with intermittent pulsation, or only with intermittent pulsation. A body-worn pump assembly is provided that is trouble-free, stable, comfortable, easy to operate, and can be verified. These pump assemblies consist of a unique housing and a unique arrangement of the pump portions in combination with a housing and cannula.

Accordingly, it is an object of the present invention to provide a housing for a body-worn pump assembly.

Another object of the present invention is to provide a body-worn pump assembly suitable for administering a predetermined amount of activator over an extended period of time.

Another object of the invention is to provide a body-worn pump assembly capable of continuous and pulse delivery.

It is a further object of the present invention to provide a body-worn pump assembly capable of pulsed dispensing of activator.

Furthermore, it is an object of the present invention to provide a simple and inexpensive pump housing and pump assembly that is capable of delivering both water-soluble and water-insoluble activators.

A further object of the present invention is to provide a body-worn pump whose operating status can be visually confirmed.

Furthermore, it is an object of the invention to provide a complete and automatic pump assembly device.

It is a further object of the present invention to provide a pump assembly having a cannula extending from the housing to the part of the body to which the pump assembly is attached.

It is a further object of the present invention to provide a pump assembly having a cannula extending from the housing at an angle that minimizes discomfort during installation and retention.

It is a further object of the present invention to provide a pump assembly for delivering an activating agent to a region of the body remote from the point of attachment of the pump assembly.

It is a further object of the present invention to provide a pump assembly having a pre-filled modular chemical reservoir.

A further object of the invention is to provide a pump assembly having a reservoir that must be filled during or before use.

A first invention provides a housing for delivering a small amount of medicine to a human body by (a) the housing having an upper surface and a side surface, the side surfaces being inclined outward from the upper surface; (b) an osmotic or absorption pump is provided within the housing, (c) a chamber is formed between the pump and the top surface of the housing, and (d) a drug to be injected into the chamber. (e) a passage is provided diagonally from said chamber, and an injection needle is provided at the body-proximate end of said passage for injecting diagonally to said body; and (f) within said housing. A housing characterized in that it includes a source of working fluid present and in contact with said pump.

A second invention is a housing for delivering a small amount of medicine to a human body, which is attached to a human body, (a) the housing has a top surface and a side surface, and the side surface is inclined outward from the top surface. (b) an osmotic or absorption pump is provided within the housing; (c) a chamber is formed between the pump and the top surface of the housing; and (d) a drug to be injected into the chamber. (e) a passageway is provided diagonally from said chamber, and an injection needle is provided at an end adjacent the body of said passageway for injecting at an angle to said body; and (f) is present in said housing. and a source of working fluid in contact with the pump; and (g) a second passageway extending from the chamber, from which medicament fills the chamber.

A third invention provides a housing for delivering a small amount of medicine to a human body, wherein (a) the housing has a top surface and a side surface, and the side surface slopes outward from the top surface. (b) an osmotic or absorption pump is provided within the housing; (c) a chamber is formed between the pump and the top surface of the housing; and (d) a drug to be injected into the chamber. (e) a passageway is provided diagonally from said chamber, and an injection needle is provided at an end adjacent the body of said passageway for injecting at an angle to said body; and (f) is present in said housing. and a source of working fluid in contact with the pump; (g) an inflatable, liquid-impermeable diaphragm disposed in the housing and dividing the housing into an upper portion and a lower portion; (h) the pump comprises: an outlet on the side of the diaphragm, and (i) a tight seal between the diaphragm, the pump and the housing, thereby directing liquid exiting the pump into the volume between the pump and the diaphragm; Relating to a housing characterized by containing:

A fourth invention provides a housing for delivering a small amount of medicine to a human body, wherein (a) the housing has a top surface and a side surface, and the side surface slopes outward from the top surface. (b) an osmotic or absorption pump is provided within the housing; (c) a chamber is formed between the pump and the top surface of the housing; and (d) a drug to be injected into the chamber. (e) a passageway is provided diagonally from said chamber, and an injection needle is provided at an end adjacent the body of said passageway for injecting at an angle to said body; and (f) is present in said housing. and (g) a source of working fluid in contact with the pump, and (g) a device for injecting a medicament into the chamber at any time.

These and other objects of the invention will become readily apparent from the following description of the invention in conjunction with the accompanying drawings.

In this specification, "working fluid" means "a fluid containing water", and "working fluid source" means "a storage part for a fluid containing water".

1 and 2, the pump assembly device 1 includes a ring-shaped adhesive 6 (omitted in FIG. 1 for simplicity) attached to a body part 5, such as the abdomen or the thigh. Fixed by The pump assembly comprises an upper wall 2 having an upper surface 3 and a side surface 4 which slopes outward from the upper surface and extends to the lower end of an annular base surface 7.
Consists of. The outer surface of the side surface 4 provides a wider slope than the top surface 3, which improves stability, adhesion and prevents inadvertent movement after application to the skin.
provides adhesion, resulting in a vector towards the skin, further acts as a thermal insulator, and
Increases the heat transfer surface of the skin and improves the thermal stability of the pump. The top wall 2 is made of a transparent material, such as polymethyl methacrylate, polycarbonate, polysulfone, PVC, medium to high density polyethylene,
Alternatively, it is suitably made from other transparent or translucent, highly modular polymers that are heat resistant, chemically inert, and capable of withstanding sterilization conditions. The transparency of the upper surface 3 allows the operating state of the pump to be visually confirmed, as will be described in detail later. In one embodiment of the invention, the top surface 3 includes a needle for introduction or filling of a pulse generator for insertion into the hole in the top surface for sealing and for providing a constant continuous flow as designed for the pump. An optional septum 8 adapted for puncturing and resealing is provided.

Inside the upper wall 2, a ring-shaped shoulder 9 is attached to the inside of the upper surface 3, and a replacement part 1 is mounted on the shoulder 9.
0 and a liquid suction pump 11 are placed on it. Both have a spring flange 1 on a compression ring 13 which is tightly engaged with the upper wall 2 at an annular groove 14.
It is fixed by 2. The spring flange is biased to pressurize the liquid suction pump 11, and tightly seals between the pump 11, the expansion membrane 10, and the shoulder 9. Expandable membrane 10
are made from relatively low module, impermeable materials such as styrene-butadiene block copolymers, natural rubber, latex rubber, silicone bars, isoprene rubber, polyurethane rubber, or mixtures thereof.

As shown in more detail in FIG.
A reinforcing device 27 such as a cross-shaped spider adapted to support and strengthen the liquid suction pump 11 is attached to the pump 3. During operation, the pump 1
1 and the inflatable membrane 10 to prevent it from being bent downwards. The spring flange 12 is placed in independently movable segments (12a, b, c and d), and the reinforcing device 27 is either made integrally with the part 13 or placed between the segments (12a, b, c and d). It is placed in the groove that has been created.

Several suction pumps are known in the literature, such as those described in the aforementioned patents, and are suitable for use herein. However, basic osmotic pumps are preferred due to their simplicity and low cost. The basic osmotic pump consists of an osmotically active, water-soluble substance, such as a common salt, and is described in U.S. Patent No. 15 by The Euwes et al.
It is contained within a rigid semi-permeable membrane 16 having one or more outlets 17 as described in 3845770 or 3916899. The maximum diameter of outlet 17 is not critical and may even be as large as the total top area, although this is not practical in manufacturing, since the liquid discharged through outlet 17 does not leave the system. The source of fluid to be absorbed by the osmotic pump 11 is within the volume defined by the compression ring 13 and is retained within the pump assembly and preferably removed from the skin by an impermeable, preferably flexible backing 19. A simple separated hydrogel 18 is preferred.

The operation of the osmotic pump shown in FIG. 2 will be explained. 18 is a working fluid made of, for example, hydrogel. The osmotic pump 11 is surrounded by a semipermeable membrane, in which a solute is enclosed. A hole 17 is provided in the semipermeable membrane. An impermeable intumescent membrane 10 is provided on the upper surface of the upper semipermeable membrane. A drug to be injected into the human body is injected into the chamber 25. Second
When the device shown in the figure is attached to the human body, water in the hydrogel (working fluid) is absorbed into the pump 1 by penetrating development.
Move to 1. A solution of the solute is then formed within the pump 11. Water is continuously transferred to the pump by osmotic development, and the volume of the solution in the pump increases, entering between the inflatable membrane 10 and the upper semipermeable membrane through the holes 17, and the inflatable membrane 10 swells upward. As the inflatable membrane swells, the drug in the chamber 25 is inserted into the human body.

The energy source for the osmotic pump comes from the osmotic pressure between the water in the hydrogel and the solute in the pump 11. The injection rate of the drug into the human body is the pump of water in the hydrogel.
Depends on the speed of transition to 1. In an essentially osmotic pump, a solution is accumulated between the inflatable membrane and the upper semipermeable membrane to the extent that the solution is formed within the pump 11.
In more complex osmotic pumps, other fluids are also discharged from the pump. In both cases, the flow rate of the pump is determined by the surface area of the semipermeable membrane, the osmotic pressure across the membrane, and the permeability of the solvent (water) through the membrane. All of these above parameters are determined by standard physical-chemical principles and are reproducible in normal manufacturing operations, and during the migration of the solvent (water) from the hydrogel according to the osmosis phenomenon, held constant.

A passage 20 and a second passage 2 are provided on the side surface 4 of the upper wall 2.
1 is attached to the base surface 7 of the wall.
The liquid is moved from the vicinity to a small chamber 25 created between the displacement wall 10 and the inside of the transparent top surface 3. One of these channels 20 is equipped with a cannula for the transfer of liquid to a remote location or a needle 22 suitable for puncturing the skin preferably at an angle of 10 to 30°, particularly preferably at an angle of 15°. The second passageway 22 is fitted with a perforated and reclosed septum 23 secured by a well-fitted fill port plug 24 for filling the displacement chamber 25 with medication. There is. The interface between the inner surface of the top surface 3 and the inner surface of the side light 4 is provided with a cross section 26 in order to eliminate the possibility of air being trapped in the corners and to facilitate complete removal of all contents in the displacement chamber 25, as described below. It is preferable to give it a rounded appearance as shown in the figure. As shown in Figures 1 and 2, although the appearance of the housing is asymmetrical, the device is symmetrical, with all sides of the device at the same angle to the horizontal plane and sloped legs on the sides. It has

It is noteworthy that embodiments utilizing septum 8 can be fabricated without passageway 21, using self-sealing septum 8 to load the device as described below.

The outline shown in FIGS. 1 and 2 has several features. The chamber 25 containing the substance to be delivered in the first place is located in the upper part of the assembly device and its contents are directly visible through the transparent top surface 3. The sides are sloped outward to provide a stable platform for the body alone and in combination with the underside of the compression cylinder 13. Furthermore, in addition to having a larger effective capacity than a cylindrical housing of the same base diameter, the sloped sides also have the advantage of being able to convert side impacts into housing forces with a downward component. I have it too. This feature allows the needle to be inserted into the skin at an angle, and
It can enhance comfort during patient use and reduce the possibility of inadvertent dislodgement of the pump or needle.

Since the flow rate of an osmotic pump varies to some degree with temperature, this ramp configuration helps maintain a relatively constant temperature close to body temperature. The large base area also improves heat transfer from the skin, and the hydrogel (working fluid) and other pump components act as a heat sink to maintain thermal balance. Additionally, the sloped sides provide a large surface area for bonding, leaving only the slightly exposed top surface exposed as the primary route for heat loss. It is insulated. If desired, the adhesive can have a centrally transparent surface, which further minimizes heat loss in environments where the pump is worn on a bare body surface instead of hidden under clothing. can be covered.
However, while the pump assembly design of the present invention facilitates direct insertion of the needle into the patient's skin at that location on the pump, it will be appreciated that the cannula may be more easily connected to inject medication.

The pump of the present invention is preferably used for dispensing up to about 5 ml of liquid activator (drug) per day. This dose is typical for drugs such as insulin, interferon, various polypeptides, and antitumor agents that are generally administered subcutaneously through the skin. This design allows for a very small and compact pump that can be used for multiple days or even weeks of administration rather than just one day. 5ml per day
The amount is delivered at a flow rate of slightly more than 0.2 ml per hour, which is within the capability of the original osmotic pump described above. Therefore, for example,
In one embodiment, the displacement chamber 25, which is approximately 2.77 cm in diameter and 0.30 cm deep, has a volume of approximately 1.6 cc and has a U-
This would be a three day dose of 100 insulin.

To use the apparatus of FIGS. 1 and 2,
Generally, the parts of the assembly device 1 are first partially assembled and sent to a pharmacist in a sterile state. type of drug,
A number of versions can be made with different flow rates determined by the drug dosage and the particular design of the suction pump or osmotic pump 11. Partially assembled device includes needle 22, fill port plug 24 and septum 23 (and if necessary 8)
It consists of an upper wall 2 having a diameter of 100 mm, to which other parts shown in FIG. 2, which are sterilely packaged, are pre-assembled.

Osmotic pumps of different sizes with different output volumes would be adjustable by the pharmacist to achieve the desired flow rate of any drug. Furthermore, the flow rate can be adjusted by changing the permeability of the liquid component of the hydrogel (working fluid), by creating another liquid permeable membrane in series with the osmotic pump, or by adding an impermeable layer in series to partially block the osmotic pump. The pharmacist places the swellable inflatable membrane 10 on the shoulder 9, incorporates a suitable osmotic pump 11 and additional diaphragms if necessary, and then tightens the assembly with a snap ring 13.

Then, a liquid activator composition (drug) of an appropriate concentration to be dispensed is filled into the drug reservoir through the septum 23 using a sterile needle. The absence of air is confirmed visually through the transparent top surface 3 and by a constant flow of liquid from the needle 20. Replacement small room 25
The chemical therein is completely isolated from the surrounding atmosphere by the seal created by the pressure exerted by the spring flange 12 on the inflatable membrane 10, the osmotic pump 11 and the shoulder 9.

The system, together with the adhesive 6, the impermeable backing film 19 and, for example, a tube of hydrogel, is then delivered to the patient or his doctor. Hydrogel 18 if used
is filled between the snap ring 13 and the surface of the pump 11, and a backing film 19 is fixed to its base, preferably by applying an adhesive thereon.

While the pump is being filled, prepare the injection site in the usual manner. Fill time is typically about 3 to 8 minutes depending on liquid, penetrant, and film thickness. The actual time is the time required for the liquid component 18 to diffuse through the semipermeable membrane wall 16 and dissolve the osmotic agent into the pump 11. The saturated solution produced in the pump 11 constantly flows out from the outlet 17 and passes through the displacement membrane 11.
Steady state is reached when chamber 25 is entered regularly and its contents are displaced through passageway 20 and cannula or needle 22. After confirming that liquid is steadily flowing out of the needle, the needle is inserted under the skin and adhesive 6 is used to secure the needle.

The use of an adhesive overlay 6 on the base of the device is such that the overlay protects and covers the injection site, reducing the possibility of subsequent infection and acting as an insulator. This is desirable. Furthermore, this overlay is a local disinfectant,
Acts as a carrier for antibiotics or local anesthetics, reducing the possibility of infection or discomfort.

The installation procedure by the patient is almost the same as the procedure for injecting insulin by the patient, which is generally performed by the patient. Because a single pump insertion can deliver insulin continuously in the same amount of time required for multiple pulse injections,
The advantages of this system are clear. Furthermore, when a pulse dosing device is used in combination with a pump assembly, this pulse dosing can be accomplished by supplementing the continuous pump's basal delivery without the need to create additional puncture holes for each pulse. It can be done. Furthermore, the assembly device is of a size that can be worn under clothing and does not detract from the appearance, making it easier for users to accept it subjectively. The needle angle is preferably between 10° and 30° (particularly preferably 15°) or smaller or larger angles, which are more acceptable to patients by minimizing discomfort during insertion and continuous use. This was found empirically.

Although the embodiments described above seek to fill the pump assembly through the second passageway 21, the second passageway 21 can be omitted and the substance to be administered can be mounted modularly. Therefore, for example, the first
As can be seen in FIGS. 1 and 12 (same parts corresponding to FIGS. 1 and 2), the substance to be administered is placed in an osmotic pump that is precalibrated to obtain any desired flow rate. Installed in pre-packaged form. The modular system consists of a prefabricated container 90 made from the same impermeable, low-module, elastomeric material used to make the displacement membrane 10. The container 90 is sized to fit tightly into the upper compartment 25 inside the top wall 2. The preferred embodiment of the container 90 is equipped with a thick annular welt 91 in series with the passageway 20 in the top wall 2. This welt is adapted to act as a septum that can be resealed to fill the container 90 and subsequently remove the filling therefrom. Furthermore, the container 90 is preferably provided with an annularly extending lip 92 suitable for fixing on the shoulder 9 in the same manner as the displacement membrane 10 in order to provide a tight liquid seal against the shoulder 9. To operate the pump assembly, a double-ended hollow needle 99 is inserted into the outlet port 20 with an inner end of sufficient length to puncture the welt 91 and provide a fluid path from the interior of the container 90 to the exterior of the pump. . In this embodiment, prepackaged drug containers and suitable osmotic pumps are supplied to the pharmacist in sterile condition and then assembled in the appropriate combination. It is supplied to the user with a double-ended needle which is inserted into the passageway at the same time as the working fluid 18 is added to create the device for the operation described above.

4, 5, 6 and 7, used alone for human pulse dosing or mounted together with a pump housing according to the invention to provide human pulse dosing to supplement basal delivery. made or created. A rotary syringe is shown.
As shown in FIGS. 4, 5 and 6, the rotary syringe 6
0 includes a cap 61, preferably at least the upper part of which is made of a transparent material, a base part 62 also made of a transparent material, and a snap ring 63 adapted to maintain a rotational relationship between the cap 61 and the base 62. It consists of Fourth
In the figure, the cap 61 and base 62 are
The internal structure of the cap 61 and base 62 are made of transparent material so that they can be viewed through the transparent top 64 of the cap 61. cap 6
The sides 65 of 1 are sloped outwardly from the top surface 64 and are knurled at 66 to facilitate rotation of the cap relative to the base. The base of the cap 61 extends to an annular flange 67, the top surface of which is flat and adapted to rest on a co-located annular flange 68 made at the outer edge of the base 62. Inside the top surface 64,
A circular elastic gasket 69 is attached. Preferably, the gasket is substantially coextensive with top surface 64 and of sufficient thickness to provide a tight seal between the interior of cap 61 and top surface 70 of base 62. The resilient plug 71 depends on the gasket 69, either forming part of it or tightly adhering thereto. The plug 71 is shaped to seal against the base surface and the sides of the storage tank 72 partitioned by an annular recess formed on the upper surface of the base 62 by machining, molding, or the like. The end of the reservoir 72 is adapted to seal the outside of the plug 71 and its inner and outer walls are such that, upon rotation of the cap 61, the piston 71 seals from the position shown in FIG. 3 to the outlet port 74.
a semi-circular wall having a center so as to move to the opposite side of the reservoir, thereby displacing the liquid contents of the reservoir 72 via a passageway 74 created in the body 62 and further through a needle or other liquid conduit 75. It is separated by. Additionally, an inlet 76 is mounted at the opposite end of the reservoir at a distance of at least the diameter of the base of the plug 71 for filling the reservoir through a resealable septum 77. Needle 75 is secured to passageway 74 by threads, a friction fit, or other suitable means, and in some embodiments, for example, septum 8 is attached to the top of the pump assembly of FIG.
are placed in series with.

The sides 78 of the cap 61 and the outer side walls 79 of the base 62 are superimposed and parallel so that the cap 61 fits over the base 62 and the side walls 78 and 79. A plurality of preferably regularly spaced pawls 80 are preferably formed across the interior sidewalls, and are preferably spaced apart from the cap 62 relative to the base 62.
A number of pawl teeth 81 formed on the external side wall are interlocked to create a pawl mechanism that allows the rotation of the device to occur only in a certain direction. In the embodiment shown, this is in a clockwise direction such that piston 71 rotates from the position shown in FIG. It drives them out. To assemble the device, first
Place the cap 61 on the base 62 and attach the flange 67.
After aligning the flange 68 with the snap spring 63
Gently place the cap 61 on top of the ring tongue 8.
2 is fixed by engaging with the annular groove 83 on the outer periphery of the base. The snap ring 63 connects the gasket 69 in the top of the cap 61 to the storage tank 7.
The cap 61 is adapted to hold the cap 61 on the base 62 with sufficient pressure to create a tight liquid seal between the tops of the base 62 so that no liquid in the cap 2 leaks from the reservoir other than through the outlet 74. Dow Corning 60 Medical allows for easier rotation of the cap 61 without binding to the base.
Either a suitable medical grade lubricant such as Fluid is used or the material used to manufacture the gasket 69 is selected to have the desired sliding properties. The scale of the rotary syringe is determined by appropriately selecting the size and spacing of the teeth 81 so that a single notch rotation of the cap releases a predetermined amount of liquid. For ease of use, the cap 61 and base 62 are provided with suitable markings, such as an arrow 84 molded or printed on the cap 61, or an indicia 85 printed or molded around the periphery of the upper surface of the base. is visible through the transparent top of the cap 61 so that the user can check the consumed and remaining amount of drug in the syringe.
When mounting the rotary syringe on the pump assembly, adhesive is coated on the bottom of the base 62 to secure the pulse dosing device and prevent the pump assembly from rotating when the cap 61 is rotated.
In use, the desired substance to be administered is added to the reservoir by inserting a suitable needle into the septum 77, filling the reservoir until a constant stream of liquid is expelled from the needle 75 and air is removed from the chamber. After the addition is complete, the needle 75 is then inserted into the septum 8 of the device as shown in FIG. 1 or 2, and the entire assembled device is applied to the skin as described above. If pulse dosing is desired on top of the continuous flow emitted by the pump, the user simply rotates cap 61 until the desired dose has been dispensed.

Although the rotary syringe is shown as a separate part of the pump assembly in Figures 4, 5, and 6, the rotary syringe is also formed as part of the pump assembly of the present invention. This can easily be made, for example, as shown in FIGS. 7 and 8, where the base part 62 of FIGS. 4, 5 and 6 is made as part of a housing as shown in FIG.
7 and 8, the same appended numerals as in the previous figures refer to the same parts and indicate other embodiments of the pump assembly 1. In FIGS. The assembly device 1 consists of a top wall 86 which is different from the top wall 2 shown in FIGS. 1 and 2, for example. That is, instead of an inlet and a passage only a passage 20 is provided, and furthermore the base 6 of the rotary syringe 60 is provided instead of the upper surface of the upper wall terminating in the transparent flat 3 as shown in FIG.
It has a shape corresponding to 2. Therefore, the upper wall 8
A ring-shaped shoulder 68, a ring-shaped snap spring groove 83, and a semicircular concave storage tank 72 are attached to the upper part of the tank 6. The storage tank 72 has a passage 74 extending from one end thereof, and serves as a liquid passage to the upper part of the replacement chamber 25. A cap 87, which corresponds to cap 61 in FIG. In this embodiment, the cap 87 has a port 88 located on the plug 71 and slopes into the chamber 72 to guide the filling needle through the top and side of the plug 71.
connected to. Plug 71 is made of a self-sealing elastomeric material to function as a displacement piston and a resealable diaphragm. On the other hand, fill passage 21 with a resealable fill septum and ports 23 and 24 is made to communicate directly with reservoir 72 just before piston 71, thereby bypassing reservoir 25. The storage tank 25 is connected to the storage tank 72 through a passage 74 . The pawl teeth and internal mechanisms of the pawl, such as the markings shown in FIGS. 3-5, are used for the same functions as in FIGS. 3-5. The explanation of the latter in FIG. 6 is omitted. In the embodiment shown, both the pulse generator and the main drug reservoir are filled by passing the needle through port 88. This fills not only reservoir 72 but also the displacement chamber through port 74.

A pulse generator is used to temporarily administer a certain amount of a drug, rather than continuously administering a small amount of the drug. That is, a drug is introduced into the chamber by a pulse generator, and the introduced drug is administered to the patient's body through an injection needle.

9 and 10, a pulsed dose delivery device is shown for use in combination with the pump housing of the present invention. Such a pulse dosing device 30 includes:
A base 31 with a number of notches of the same or different size and, in this embodiment, of sufficient length to penetrate the base and into the diaphragm of the top of the pump housing as shown in FIGS. 1 and 2. Fluid delivery grooves 33 are connected to each notch to move fluid to a passageway 34, shown as a small gauge needle 35.
It consists of A replacement part 36 is placed on top of the base 31 and is provided with a number of protrusions of the same size and position as the notches 32 of the base 31. The replacement part 36 is glued or sealed to the base 30 so that liquid from the reservoir confined between the notch 32 and the protrusion 37 flows only through the groove 33 and into the passageway 34. The replacement part is protrusion 37
37a in the recess of the notch 32, permanently opposing and exactly matching the inner surface of the notch 32, and directing the contents of the reservoir through the passage 33 from the needle 35 to the upper wall 2.
Preferably, it is permanently deformed so as to move it into the replacement chamber 25 of. The pulse dispensing device 30 is preferably fitted with a cap 38 which is tightly engaged with the side of the base 31, for example.
The lower part of the base is attached to the housing 2 using adhesive 39.
Preferably, it is permanently adhered to the top of the. Preferably, all parts of the pulse dosing device are transparent so that the operating status of the displacement chamber of the pump assembly device can be visually observed and the operation confirmed during dosing. Furthermore, it is clear that this pulse dosing device will become part of the housing in the same way as the rotary syringe of FIG. It is noteworthy that this dispensing device 30 is generally the only one described herein. Although we have described a specific pulse dosing device that can be used with the pump assembly of the present invention, it will be readily appreciated that other continuous flow pulse dosing devices may also be used. Thus, for example, a hypodermic needle could be inserted into the septum 8 for pulse dosing, or the septum 8 could be replaced by a displacement piston assembly device as described in US Pat. No. 4,340,048. Additionally, other pulsed dose generators may be used as part of the housing assembly.

FIG. 13 shows the present invention which uses an osmotic pump to create and pressurize the substance to be administered, rather than utilizing a displacement element to expel the drug from a reservoir under the influence of a working fluid generated by a suction pump. Another aspect of is shown. Figure 1 or 2
The same housing used in the illustrated embodiment can be used in this embodiment of the invention. For convenience, the same elements used in Figures 1 and 2 are utilized in Figure 2;
Replacement part 10 and pump 11 have been replaced by spatial element 56 and suction pump 55. Although any suction pump mechanism can be used to create pump 55, the simplest and preferred mechanism for water-soluble drug delivery is the one described above.
It consists of an osmotic pump with a chemical that is an osmotic agent as described in the Tteeuwes et al. patent. Although drugs of low solubility or insolubility can be administered from other types of suction pumps known in the literature, their compositions in the present invention are more conveniently administered from the embodiments of FIGS. 1 and 2. Ru. In the embodiment of FIG. 13, the pump 55
is a water-soluble membrane, all known in the literature, consisting of a semi-permeable membrane 57 and having an outlet orifice 58, mixed with other osmotically active substances sufficient to administer the contents of the pump 55 upon exposure to water. Osmotically active compositions such as drugs or water-insoluble drugs are included.
In this embodiment, the pump 55 is located in the portion of the vessel that forms the displacement chamber 25 of FIGS. 1 and 2. To minimize device space and start-up time, the pump 55 is sized to fit into the top wall 2 on a curved surface between the top surface 3 and the side surface. To ensure a tight seal, a hollow spacer element 56 is used, the lower part of which contacts the spring 12 and is made to form a seal between the shoulder 9 and the leaf spring part 12. In operation, the hydrogel is filled in the center of the spacer part 56 and in the lower part of the container and fixed by the backing 19. In this aspect of the invention, each part 2, 13, 56 and 55
After it is assembled, it is sent to the doctor or patient. Upon insertion, the container is filled with hydrogel 18 and a bucking component is used. After setting up the device, the upper volume of pump 5 is filled to create a steady flow from needle 22. In this embodiment, the start-up time is longer because the small volume of space above the pump 55 must initially be filled before a steady flow is obtained. If the volume of space is deemed too large, a solid chemical resistant plastic may be placed in the top of pump 55 to provide a passageway for liquid transfer between outlets 58 and 20. After confirming steady flow, needle 22 is inserted into the skin and adhered as described above. Although a spacer element 56, as shown in FIG. 13, is used in the housing assembly apparatus for various aspects of the invention, it should be recognized that this spacer element is not critical to the invention. Therefore, displacement membrane 16 can be omitted and pump 55 can be used in the same manner as pump 11 of FIG. According to this method, it is preferable to modify the internal shape of the housing to minimize the spatial volume.

Example: The capacity of the rotary syringe is 0.75ml, and the capacity of the membrane agent storage tank is 0.75ml.
A pump assembly as shown in Figures 7 and 8 was constructed for administering insulin of 1.5 ml. The osmotic pump consisted of a 2.94 cm diameter, 0.15 cm thick tablet coated with 0.038 cm of Eastman Kodak cellulose acetate E398-10, with a 0.4 cm diameter orifice on the top surface. The core of the tablet is 65% (by weight) NaCl, 20%
Polyox WRPA3154 consists of polyethylene oxide and 15% polyethylene glycol 20,000. The displacement membrane was made from a 0.03 cm thick styrene butadiene copolymer elastomer sheet. The housing is made from high-impact polycarbonate with a maximum base diameter of 6.35 cm, a top surface diameter of 2.86 cm, and a height of approximately 1.45 cm.
The A30 gauge needle was set at a 15° angle to the base.
Hydrogel was used as the starting fluid source, and the continuous flow rate of the device was approximately 10 μ/hr. with a maximum duration of 150 hours.
With each successive click (pulse) of the rotary syringe
It was 20μ0 pulse. Using U-100 insulin, this system delivered 2 U of insulin per pulse with a continuous delivery rate of 1 u/hr.

Although this pump has been described as being suitable for delivering fluid into the body at the location of the device, the needle may be inserted into a catheter for delivering the administered fluid to a location remote from where the pump is attached. Alternatively, it is obvious that it can be replaced by a canyule. The cannula connects one end to the outlet port and the other end to the other as in a normal Y-set so that the medication delivered from the pump can be supplemented with other medications. It is connected to a needle that is connected to a device or inserted directly into the body.
Alternatively, the outlet of the pump assembly can be connected, for example, to a nasopharyngeal tube for administering small doses of medication to the gastrointestinal tract, or to a Foley catheter for delivery to the bladder. Therefore, the particular purpose for which a delivery activator is used is
Although not critical to the invention, it is also possible to deliver the activating agent to a remote location for whatever purpose is desired, as well as direct administration into the body.

Although the present invention has been described in terms of individual aspects,
Many modifications will occur to those skilled in the art without departing from the scope of the invention, which is limited by the claims.

In the present invention, any pump other than an osmotic pump can be used as the liquid suction pump. For example, in the embodiment shown in FIG. Absorption pumps using water-swellable polymers such as ethylene oxide can also be used in the present invention. In the absorption pump, water in the hydrogel passes through the microporous membrane into the water-swellable polymer, and the swelling membrane swells due to water pressure, forcing the drug in the chamber 25 into the body. This absorption pump works without osmosis,
The pumping rate is then controlled by the rate of diffusion of water into the water-swollen polymer and the porosity and thickness of the microporous membrane.

The embodiments of the present invention are as follows.

1. In a housing that is attached to the human body to deliver a small amount of a specific drug or therapeutic agent (drug) to the human body, (a) the housing has a top surface and a side surface that is sloped outward from the top surface; (b) ) an osmotic pump or an absorption pump is provided within the housing; (c) a chamber is formed between the pump and the interior of the top surface of the housing; (d) a drug to be injected is present within the chamber; ) the chamber is provided with an oblique passageway and an infusion needle provided at an oblique body-proximal end of the passageway; and (f) a source of working fluid residing within the housing and in contact with the pump. A housing characterized by:

2. The housing of item 1 above, wherein the injection needle is at an angle of 10 to 30 degrees with respect to the surface of the body.

3. The housing of item 2 above, wherein the angle is approximately 15°.

4. The housing according to item 1 above, wherein at least a portion of the housing is transparent.

5. The housing according to item 1 above, wherein the intersection of the top surface and the side surface is rounded.

6. In a housing that is attached to the human body to deliver a small amount of a specific drug or therapeutic agent (drug) to the human body, (a) the housing has a top surface and a side surface that is sloped outward from the top surface; (b) ) an osmotic pump or an absorption pump is provided within the housing; (c) a chamber is formed between the pump and the interior of the top surface of the housing; (d) a drug to be injected is present within the chamber; ) said chamber is provided with an oblique passageway and an infusion needle provided at an oblique body-proximal end of said passageway; (f) a source of working fluid residing within said housing and in contact with said pump; g) a second passageway extending from said chamber;
A housing characterized in that the housing comprises: a passageway through which a drug is filled into the chamber.

7. The housing of claim 5, wherein the second passageway extends through the top surface of the housing.

8. The housing of claim 5, wherein said second passageway terminates at a portion of said side surface adjacent an adjacent end of the body.

9(a) an inflatable, liquid-impermeable diaphragm disposed in the housing and dividing the housing into an upper part and a lower part; (b) the pump has an outlet on the diaphragm side; and (c) The housing according to item 1 above, which is a combination of the diaphragm, the pump, and the housing, and a sealing part that provides a tight liquid seal between the pump and the housing, and confines the liquid flowing out of the pump into the volume between the pump and the diaphragm. Equipment including.

10. The device of claim 9, further comprising the pumping working fluid in the housing and wherein upon activation the pump defines a boundary between the pump and the diaphragm by contact with the pump surface. .

11. The apparatus of claim 10, further comprising a transferred boiling liquid confined in the upper portion of the housing.

12. The device of claim 11, wherein the liquid to be transferred is contained in a configurable liquid-impermeable bag contained within the housing.

13. The device of item 12 above, wherein the septum is integrated with the bag.

14. The device according to item 12 or 13, further comprising a liquid transfer component for transferring liquid between the interior of the bag and the passageway.

15. The device according to item 10 above, further comprising reinforcing parts to increase the hardness of the suction pump.

16. The device of claim 9, further comprising (a) a component for producing a fluid pulse (occasional filling of the chamber with drug) bounded in the upper portion of the housing.

17. Apparatus according to claim 16, wherein at least a part of the part for producing a liquid pulse is made as part of the housing.

18. A device according to claim 16, wherein said part for producing a liquid pulse is a separate unit from said housing and has an outlet for transferring liquid to the top of said container.

19 No. 16 above, wherein the pulse generator is a rotary syringe.
Equipment listed.

20 The bag includes a circumferentially extending self-sealing welt positioned to cover the end of the passageway adjacent to the interior top surface of the container, whereby the needle is inserted into the welt. 15. The apparatus of claim 14, wherein the bag is filled and emptied by opening the bag.

21. The device of claim 20, wherein the liquid transfer component includes a hollow component connected to the passageway, the inner end of which extends through the bag at the welt.

22 A hermetic, configurable, liquid-impermeable bag having a base surface and a self-sealing welt extending around the bag substantially parallel to the base surface and spaced apart from the base surface. Section equipment.

23. The apparatus of claim 22, further including a peripheral flange being part of the base surface and extending radially outwardly from the base surface.

24. A device according to claim 22 or 23, further comprising a liquid volume filling said bag.

25. The pump assembly of claim 23, wherein at least an upper surface of the housing above the container is transparent.

26. The device of claim 1, having a membrane in a chamber in the upper part of the housing.

27 In a device that is worn on a human body to deliver a small amount of a specific drug or therapeutic agent to the human body, the device includes: (a) the housing has a top surface and a side surface that slopes outward from the top surface; b) an osmotic pump or an absorption pump is provided within the housing; (c) a chamber is formed between the pump and the interior of the top surface of the housing; (d) a drug to be injected is present within the chamber; e) said chamber is provided with an oblique passageway and an infusion needle provided obliquely at the body-proximal end of said passageway; and (f) a source of working fluid residing within said housing and in contact with said pump. A housing device comprising:

28 In a device that is worn on a human body to deliver a small amount of a specific drug or therapeutic agent to the human body, the device includes: (a) the housing has a top surface and a side surface that slopes outward from the top surface; b) an osmotic pump or an absorption pump is provided within the housing; (c) a chamber is formed between the pump and the interior of the top surface of the housing; (d) a drug to be injected is present within the chamber; e) said chamber is provided with an oblique passageway, the body-proximal end of said passageway being provided with an infusion needle obliquely; and (f) a source of working fluid residing within said housing and in contact with said pump; (g) a fluid pulse generating member in communication with the chamber; and (h) a drug to be injected residing within the fluid pulse generating chamber and the fluid pulse generating member.

29. The device according to paragraph 28 above, wherein the pulse generator is a rotary syringe.

30 The rotary syringe includes first and second relatively rotatable members, the first member having an arcuate groove in a surface thereof, and the second member sealingly within the groove. and having alternating piston elements adapted to be received by the grooves and forming a fluid reception with said grooves, said piston elements being adapted to be received when the two members are rotated relative to each other.
30. The device of claim 29, including an external member applied across from a first end to a second end of the arcuate groove and providing fluid communication between the second end of the groove and the chamber. .

31. The apparatus of claim 30, wherein one of the rotatable members is formed at the outer top surface.

32. Said means for generating a fluid pulse comprises: (a) at least one container of a medicinal liquid having a wall portion formed from a permanently deformable blister arranged to substantially completely displace the contents of said housing; , and (b) said twenty-eighth part including external means for providing fluid communication between said housing and said compartment.
Apparatus described in section.

[Brief explanation of drawings]

FIG. 1 is an overall view of a pump assembly device according to the present invention. FIG. 2 is a cross-sectional view of FIG. 1 taken along line 2-2. 3 is a plan view of the components of the embodiment of FIG. 2; FIG. FIG. 4 is a top view of a rotary syringe pulse medication for use in conjunction with a pump assembly according to the present invention. FIG. 5 is a side view of the installation of FIG. 3; FIG. 6 is a side, exploded view of the apparatus of FIGS. 4 and 5 with parts separated. FIG. 7 is a plan view of another embodiment of the invention in which the pulse generator forms part of a pump assembly. FIG. 8 is a cross-sectional view of the embodiment of FIG. FIG. 9 is a top view of another pulse dosing article for use in conjunction with the pump assembly of the present invention. FIG. 10 is a sectional view taken along line 10-10 in FIG. 9. FIG. 11 is an overall prefilled dosage product according to the present invention. FIG. 12 is a cross-sectional view of an embodiment of the pump assembly of the present invention utilizing the dispenser of FIG. 11; 13th
12 is a cross-sectional view of another embodiment of a pump assembly utilizing the dosing device of FIG. 12 in accordance with the present invention.

Claims (1)

[Scope of Claims] 1. A housing to be attached to a human body for delivering a small amount of a specific drug or therapeutic agent (or drug) to the human body, (a) the housing has an upper surface and a side surface, and the side surface is (b) an osmotic or absorption pump is provided within the housing; (c) a chamber is formed between the pump and the top surface of the housing; (d) a medicament to be injected within said chamber; (e) a passage is provided diagonally from said chamber, and an injection needle is provided at an end of said passageway adjacent to the body for injecting diagonally to said body; and (f) a source of working fluid within the housing and adjacent the pump. 2. The housing of claim 1, wherein the injection needle is at an angle of 10 to 30 degrees with respect to the surface of the body. 3. The housing of claim 2, wherein said angle is approximately 15 degrees. 4. The housing according to claim 1, wherein at least a portion of the housing is transparent. 5. In a housing that is attached to a human body and is used to deliver a small amount of a specific drug or therapeutic agent (or drug) to the human body, (a) the housing has a top surface and a side surface, and the side surface is inclined outward from the top surface. (b) an osmotic or absorption pump is provided within said housing; (c) a chamber is formed between said pump and the top surface of said housing; and (d) an osmotic or absorption pump is provided within said chamber. a medicament is present; (e) a passageway is provided diagonally from said chamber, and an injection needle is provided at the body-proximate end of said passageway for injecting diagonally to said body; and (f) within said housing. a source of working fluid present and adjacent to the pump; and (g) a second passageway extending from the chamber, from which medicament fills the chamber. housing. 6. In a housing that is attached to the human body to deliver a small amount of a specific drug or therapeutic agent (or drug) to the human body, (a) the housing has a top surface and a side surface, and the side surface is inclined outward from the top surface. (b) an osmotic or absorption pump is provided within said housing; (c) a chamber is formed between said pump and the top surface of said housing; and (d) an osmotic or absorption pump is provided within said chamber. a medicament is present; (e) a passageway is provided diagonally from said chamber, and an injection needle is provided at the body-proximate end of said passageway for injecting diagonally to said body; and (f) within said housing. a source of working fluid present and adjacent to the pump; (g) an inflatable, liquid-impermeable diaphragm disposed within the housing and separating the housing into an upper portion and a lower portion; (h) the pump; has an outlet on the side of the diaphragm, and (i) is tightly sealed between the diaphragm, the pump, and the housing, thereby directing liquid exiting the pump to the volume between the pump and the diaphragm. A housing characterized in that it is enclosed and includes. 7 In a housing that is attached to the human body and for delivering a small amount of a specific drug or therapeutic agent (or drug) to the human body, (a) the housing has a top surface and a side surface, and the side surface is inclined outward from the top surface. (b) an osmotic or absorption pump is provided within said housing; (c) a chamber is formed between said pump and the top surface of said housing; and (d) an osmotic or absorption pump is provided within said chamber. a medicament is present; (e) a passageway is provided diagonally from said chamber, and an injection needle is provided at the body-proximate end of said passageway for injecting diagonally to said body; and (f) within said housing. a source of working fluid present and adjacent to said pump; and (g) a device (pulse generator) for injecting medicament into said chamber from time to time. 8. The housing of claim 7, wherein the pulse generator is attached to the housing. 9. The housing of claim 7, wherein the pulse generator is not attached to the housing and is coupled to the housing when injecting the drug into the chamber. 10. The housing of claim 9, wherein the pulse generator is a rotary syringe. 11. The rotary syringe includes two relatively rotatable members, one member having an arcuate groove in its face, and the other member being sealingly received within the groove. and having alternating piston elements suitable for moving the groove from the first end to the second end of the arcuate groove when the two members are rotated relative to each other and forming a fluid receiving portion with the groove. 11. The housing of claim 10, including an external member applied across the channel and providing fluid communication between the second end of the channel and the chamber. 12. The housing of claim 11, wherein the housing is formed at the outer top surface of one of the rotatable members.