Method, system and device for drug delivery and treatment

Abstract

Methods, systems, and devices for drug delivery and treatment are disclosed. The drug delivery method can be used for the treatment of periprosthetic joint infection (PJI, Periprosthetic Joint Infection) and other health conditions such as orthopedic joint infections. The drug delivery methods and devices may include a fluid delivery mechanism that may include a fluid reservoir that may be filled with a high concentration of an antibiotic formulation. The high concentration antibiotic formulation may include an antibiotic at a concentration ranging from about 10 mg / ml to about 200 mg / ml, can be dissolved in an aqueous solution, and then can be stored under refrigerated or frozen conditions. The fluid in the fluid reservoir may be administered in discrete doses by a medical device or instrument.

Description

Background Technology

[0001] For many diseases, treatments are more effective when administered with preferential action on the target anatomical region. For example, in treating periprosthetic joint infection (PJI), delivering antibiotics intramuscularly via bolus injection into the infected joint cavity is more effective than intravenous administration. However, such formulations must contain high concentrations of antibiotic drug components while maintaining physical and chemical stability for storage and administration to patients, minimizing the dosage required.

[0002] Under current treatment standards, reconstituted vancomycin solution is typically administered intravenously to patients with periprosthetic joint injury (PJI), allowing the drug to directly enter the systemic circulation. Therefore, only a small portion of the administered antibiotic reaches the periprosthetic joint cavity, potentially resulting in insufficient therapeutic concentrations at the site of infection. Another delivery method involves using antibiotic-containing prosthetic cement or materials, which can deliver high doses of antibiotics to the infected joint, but the duration of action is very short. Both methods (intravenous administration and antibiotic-loaded materials) not only risk failing to effectively clear the infection due to insufficient therapeutic concentrations but also increase the risk of antibiotic resistance in the infected pathogen, making treatment and eventual eradication of the infection even more difficult. Summary of the Invention

[0003] The exemplary embodiments described in this invention generally relate to a fluid delivery device and method for treating orthopedic joint infections, a fluid reservoir for delivering a high-concentration drug formulation to an infected joint region, and a method for preparing a high-concentration drug formulation.

[0004] A fluid delivery device may include a fluid reservoir filled with a high-concentration pharmaceutical formulation. In one exemplary embodiment, the high-concentration formulation may contain an antibiotic solute at a concentration of about 10 mg / mL to about 200 mg / mL, such as vancomycin hydrochloride, tobramycin, gentamicin, rifampin, daptomycin, ceftriaxone, linezolid, or cefazolin, wherein the antibiotic solute is dissolved in an aqueous solvent to generate the high-concentration formulation, such as about 5% glucose aqueous solution (D5W), buffered saline, about 10% ethanol aqueous solution, or physiological saline solution. In some embodiments, the high-concentration pharmaceutical formulation may contain an antimicrobial preservative, such as phenol, benzyl alcohol, phenoxyethanol, methylparaben, and propylparaben, or a combination of multiple antimicrobial preservatives. In some embodiments, the high-concentration antibiotic formulation may be stored under refrigerated or frozen conditions to maintain physical and chemical stability, for example, refrigeration conditions may be 2-5°C. Furthermore, in one exemplary embodiment, the fluid reservoir may be connected to a medical implant or other medical device, such as an infusion pump and / or catheter, for routine administration. Attached Figure Description

[0005] Example Figure 1A The operating position of an alternative embodiment of the fluid delivery device is shown.

[0006] Example Figure 1B The storage location of an alternative embodiment of the fluid delivery device is shown.

[0007] Example Figure 2 An embodiment of a fluid delivery method using a fluid delivery device is shown. Detailed Implementation

[0008] Various aspects of the present invention are disclosed in the following description with reference to specific embodiments of the invention. Alternative embodiments may be conceived without departing from the spirit or scope of the invention. Furthermore, to avoid obscuring relevant details of the invention, well-known elements in exemplary embodiments of the invention will not be described in detail or will be omitted. Further, for ease of understanding of the following description, several terms used in the invention will be explained.

[0009] As used in this invention, "exemplary" means "serving as an example, instance, or illustration." The embodiments described in this invention are not limiting, but merely exemplary. It should be understood that the embodiments described in this invention should not be construed as being more preferred or advantageous than other embodiments. Furthermore, the terms "embodiments of the invention," "embodiments," or "the invention" do not require that all embodiments of the invention include the disclosed features, advantages, or modes of operation.

[0010] In one or more exemplary embodiments, the present invention may provide a drug delivery method and apparatus.

[0011] In one exemplary embodiment, the drug delivery method and apparatus can be used to treat, for example, periprosthetic joint infection (PJI) or other orthopedic infections such as osteomyelitis, suppurative arthritis, or fracture-related infections. It should be understood that in some embodiments, the drug delivery method and apparatus can be used to treat other conditions, such as implant-related infections and other joint conditions. The drug delivery method and apparatus may include a fluid delivery mechanism for administering fluid to an infected joint via an intra-articular cavity (IA) or other part of the body. In some embodiments, the fluid delivery mechanism may include a fluid reservoir containing a syringe or cartridge. In some embodiments, the filled reservoir may contain a high concentration of antibiotic preparations. In other embodiments, the fluid reservoir may contain other fluids, such as saline or hyaluronic acid irrigation solutions, different fluids with clinical benefit, or combinations of multiple fluids, wherein the combination of multiple fluids is, for example, a mixture of saline, hyaluronic acid, local anesthetics, steroids, and antibiotics. In some embodiments, the fluid reservoir can deliver fluid to the infected area via the fluid delivery mechanism. In some embodiments, the fluid delivery mechanism may include an internal delivery mechanism, such as an infusion pump, which may be connected to an external delivery mechanism, such as a patient-worn medical implant or other medical device. In other embodiments, the fluid reservoir may otherwise deliver fluid to the infected area.

[0012] In one or more exemplary embodiments, the present invention may provide a method for preparing a high-concentration antibiotic formulation. A high-concentration antibiotic formulation for use in the fluid delivery device may comprise an antibiotic in a concentration ranging from about 10 mg / mL to about 200 mg / mL, dissolved in an aqueous solution, and in some embodiments, may be stored under refrigerated or frozen conditions. Some embodiments may include about 5% glucose aqueous solution (D5W) as a diluent. Other embodiments may include about 10% ethanol aqueous solution. Still other embodiments may include standard saline solution or buffered saline solution. In one exemplary embodiment, the high-concentration antibiotic formulation may be a vancomycin hydrochloride formulation, the concentration of which may be from about 50 mg / mL to about 100 mg / mL, and may use, for example, about 5% glucose aqueous solution (D5W) as a diluent, and may be stored under refrigerated or frozen conditions to extend shelf life, for example, to about 4 weeks or longer. In other embodiments, other antibiotics, such as tobramycin, gentamicin, rifampin, and cefazolin, may be used under similar conditions.

[0013] The present invention provides an exemplary method of using the fluid delivery device. The drug delivery method may include a fluid delivery mechanism comprising a fluid reservoir containing a high concentration of an antibiotic preparation or other drug fluid. In one exemplary embodiment, the fluid may be pre-filled. In one exemplary embodiment, the fluid reservoir may be a cartridge or syringe. The process of pre-filling the high concentration of the antibiotic preparation or other fluid into the fluid reservoir may be performed by, for example, a manufacturer or a specialty pharmacy. In a next step, the pre-filled fluid reservoir may be delivered to a healthcare professional or directly to a patient. In a next step, the patient or healthcare professional may connect the pre-filled fluid reservoir to the fluid delivery mechanism, such as a medical implant or other medical device or instrument, such as an infusion pump that can be worn by the patient.

[0014] In one exemplary embodiment, antibiotics or other solvents can be stored as lyophilized powders due to their relatively short shelf life after reconstitution into an aqueous solution. In these cases, the fluid reservoir may comprise two or more chambers with a diaphragm / barrier between them. In some embodiments, one or more chambers may contain powder, and one or more other chambers may contain diluent, the barrier being ruptured by a patient or nurse / other medical professional to allow the powder to mix with the diluent to form a pharmaceutical fluid.

[0015] In one exemplary embodiment, the fluid reservoir may be manufactured with a breakable diaphragm / barrier that separates the lyophilized powder from the diluent. In this embodiment, the fluid delivery method may include an intermediate step of mixing the lyophilized powder with the diluent to reconstitute the solution by breaking the barrier.

[0016] In the next step, fluid from the fluid delivery device may be applied to the treatment site via the fluid delivery mechanism. In the next step, a predetermined dose of fluid may be delivered by bolus administration, which should be understood as administering discrete amounts of fluid over a specific time period. The bolus dose is considered fully delivered when the fluid reservoir is emptied, the predetermined dose of fluid has been pumped, and / or a specific time period has elapsed. In some embodiments, the fluid reservoir may be replaced. In some embodiments, some or all of these steps may be repeated periodically, for example, once or twice daily, or every other day, until treatment is complete. In the final step, treatment is complete, and, for example, the fluid delivery mechanism may be removed.

[0017] like Figure 1A-Figure 1B As shown, Figure 1A-Figure 1BAn embodiment of the fluid delivery device 100 in an operating position 150 and an embodiment in a storage position 160 are shown and described. The fluid delivery device 100 may include an internal delivery mechanism 102, which may be implanted in a patient and connected to, for example, an infected joint cavity. It should be understood that, in use, the internal delivery mechanism 102 may be placed inside the patient. The internal delivery mechanism 102 may be connected to a first side of a pivot point 104, which should be understood to be located on the patient's skin surface. The pivot point 104 may be further connected to a sleeve 106, which may cover a portion of the internal delivery mechanism 102, for example, the sleeve 106 may be about 15 to 30 mm in length. It should be understood that the sleeve 106 may allow tissue to grow into the sleeve 106. A second side of the pivot point 104 may be further connected to an external delivery mechanism 108, which may be connected to a delivery module 110. It should be understood that in some embodiments, the internal delivery mechanism 102 and the external delivery mechanism 108 may be two parts of the same catheter that pass continuously through the pivot point 104, while in other embodiments, the internal delivery mechanism 102 and the external delivery mechanism 108 may be separate mechanisms that are fluid-tightly attached to both sides of the pivot point 104, respectively. The delivery module 110 may include a cap 112. When not in use, the cap 112 may protect the site and the infusion tubing connector, which in one embodiment may be a Luer lock connector. In some embodiments, the cap 112 may include a magnet and / or locking threads to secure the cap 112 to the fluid reservoir 114. The delivery module 110 may be attached or secured to the patient by, for example, an adhesive patch 116, which may be a pressure-sensitive adhesive patch. The delivery module 110 may be attached to the adhesive patch 116 by, for example, a hook-and-loop pad or a patch. The fluid reservoir 114 can also be attached or secured to the patient in a similar manner. In some embodiments, the cap 112 can be connected to the fluid reservoir 114 by a tether to prevent loss.

[0018] It should be understood that in some embodiments, the internal delivery mechanism 102 and the external delivery mechanism 108 may be a single delivery mechanism extending from the portion implanted within the patient to the portion outside the patient via the pivot point 104. In one embodiment, the delivery mechanism may be a continuous flexible tube, such as a catheter, with a diameter of about 1.0 to about 3.0 mm. The sleeve 106 may be made of a material that promotes skin and wound healing and provides adhesion to enhance closure of the surrounding skin, which should be understood to reduce the risk of infection. In some embodiments, the sleeve 106 may be made of, but is not limited to, polyester materials (such as polyester fiber) and / or metal mesh materials (such as titanium or stainless steel). In other embodiments, the sleeve 106 may also be a polymer extrusion.

[0019] The pivot point 104 ensures that the internal delivery mechanism exits the body at a small angle of curvature, preventing accidental snagging and / or kinking between the internal and external delivery mechanisms. The pivot point 104 may be further configured to maximize the exposed area of ​​the sleeve 106, facilitating cleaning and sterilization of the sleeve 106. The pivot point 104 may further include two or more suture points to secure it to the skin during implantation of the internal delivery mechanism 102. The pivot point 104 may be designed to be detachable and easily removed from the internal delivery mechanism 102 for easy removal upon completion of treatment. It should be understood that once the pivot point 104 is removed, a circumferential cutting tool can be used to cut around the sleeve 106 to cut the skin and soft tissue, and the circumferential cutting tool can be fitted over the catheter to completely remove the fluid delivery device 100.

[0020] The delivery module 110 may further include a check valve to prevent fluid backflow. The check valve reduces the outflow of compounds, saline, or bodily fluids through the infusion tubing connector from the patient during connection, removal, or disuse of the infusion tubing. In some embodiments, the delivery module 110 may have an operating position 150 and a storage position 160. In the storage position 160, the delivery module 110 is folded and secured within the fluid reservoir 114, thereby reducing the profile height of the delivery module 110 and preventing snagging or jamming when not in use. In some embodiments, the delivery module 110 may be a single-use module, while in other embodiments, the module may be a reusable and / or refillable module.

[0021] The fluid reservoir 114 can prevent fluid from flowing out of the catheter when no infusion tubing is connected, by means of, for example, the cap 112, the check valve, or both. In some embodiments, the cap 112 can provide visual or tactile feedback when properly positioned, for example by using a magnet. In some embodiments, a portion of the external delivery mechanism 108 can be further secured several centimeters from the pivot point 104 to relieve stress, and in conjunction with skin sutures, to relieve stress as the delivery mechanism enters the body.

[0022] It should be understood that the fluid delivery device 100 can be connected to an external delivery mechanism 108, and the fluid delivery device 100 can be used to treat areas within a patient's body, such as for irrigation treatments, i.e., cleaning infected joints or other areas without removing prosthetic hardware; and / or revision treatments, such as cleaning, removing, or replacing prosthetic hardware. It should also be understood that the connection between the fluid delivery device, the infusion tubing, and any external structure (e.g., the delivery module) can be a liquid-tight connection.

[0023] like Figure 2 As shown, Figure 2 An embodiment of a method for a fluid delivery system is shown, which may use, for example, the fluid delivery device 100.

[0024] In the first step 202, the fluid delivery device 100 can be implanted into the patient and sutured to the skin surface. The fluid delivery device should be positioned such that a portion of the device is implanted into the patient and another portion is located outside the patient's skin. In the next step 204, the external delivery mechanism 108 can be housed within the storage module during implantation. In the next step 206, when the patient needs medication, the fluid reservoir 114 can be connected to the delivery module 110. In the next step 208, the delivery module 110 can be connected to the external delivery mechanism 108, and the delivery module 110 can be worn by the patient during fluid delivery. In the next step 210, the delivery module 110 can be activated, and fluid from the fluid reservoir 114 can be pumped to the treatment site via the delivery mechanism. In the next step 212, once pumping is complete (i.e., the completion of pumping may occur when the fluid reservoir 114 is emptied, a predetermined amount of fluid has been pumped, and / or a specific time has elapsed), the delivery module 110 can be removed from the external delivery mechanism 108 and stored. In some embodiments, steps 206-212 may be repeated periodically (e.g., once daily, or every other day) until treatment is complete. Treatment may be completed in the final step 214, for example, after the entire course of treatment has been completed, after a specific duration (e.g., 6 weeks, 2 months), or after the initial problem (e.g., PJI) has been cured or adequately treated. In some embodiments, an examination may be performed after a specific duration to determine whether treatment should continue. It should be understood that additional surgery may be performed after treatment is completed, and the fluid delivery device 100 may be removed. The external delivery mechanism 108 may be the portion of the fluid delivery device 100 located outside the patient's skin.

[0025] The foregoing description illustrates the principles, preferred embodiments, and operation of the present invention. However, the present invention should not be construed as limited to the specific embodiments disclosed above. Those skilled in the art will be able to understand other variations of the above embodiments.

[0026] Therefore, the above embodiments should be considered illustrative rather than restrictive. Accordingly, those skilled in the art can make modifications to the embodiments without departing from the scope of protection defined by the following claims.

Claims

1. A fluid delivery device, characterized in that, include: Pre-filled fluid storage tank; A high-concentration drug fluid, wherein the high-concentration drug fluid is stored in the fluid reservoir; A delivery module that facilitates the delivery of the high-concentration drug fluid from the reservoir to the anatomical area requiring treatment via a delivery mechanism; An external delivery mechanism, which is connected to a pivot point and is located outside the patient's skin; An internal delivery mechanism that delivers the high-concentration drug fluid directly to the affected site at a bolus dose; A pivot point connecting the internal delivery mechanism and the external delivery mechanism; A sleeve made of a material that promotes skin and wound healing.

2. The fluid delivery device according to claim 1, characterized in that, The high-concentration drug solution includes: Antibiotics, wherein the concentration of the antibiotics is 10-200 mg / mL; and An aqueous solvent, wherein the aqueous solvent is used as a diluent.

3. The drug delivery device according to claim 2, characterized in that, The antibiotic is vancomycin hydrochloride at a concentration of 50-100 mg / mL; and The diluent is a 5% glucose solution.

4. The fluid delivery device according to claim 1, characterized in that, The formulation also contains an antimicrobial preservative.

5. The fluid delivery device according to claim 1, characterized in that, The pivot point is detachable and easily removed from the internal delivery mechanism.

6. The fluid delivery device according to claim 1, characterized in that, The pivot point is provided with multiple suture points, which are used to fix the pivot point to the skin.

7. The fluid delivery system according to claim 1, characterized in that, The bolus dose is administered periodically throughout the treatment.

8. The fluid delivery system according to claim 1, characterized in that, The bolus dose is administered by a medical professional.

9. A fluid delivery method, characterized in that, include: Preparation of high-concentration drug solutions; The high-concentration drug solution is stored under refrigeration or freezing conditions; Prefill the high-concentration drug fluid into the fluid reservoir; Connect the pre-filled fluid reservoir to the delivery module; The fluid is pumped to an external delivery mechanism via the delivery module; The fluid is transferred from the external delivery mechanism to the internal delivery mechanism via a pivot point; The fluid is delivered below the skin barrier via the internal delivery mechanism; The drug is delivered from the internal delivery mechanism to the affected site at a bolus dose; The sleeve, located on the internal delivery mechanism, promotes skin and wound healing.

10. The fluid delivery method according to claim 9, characterized in that, The preparation of the drug solution includes: Reconstitute the antibiotic solution to a concentration of 10-200 mg / mL; The antibiotic was diluted and dissolved using an aqueous solvent.

11. The fluid delivery method according to claim 10, characterized in that, The reconstitution of the antibiotic solution includes: diluting vancomycin hydrochloride with 5% glucose solution to a concentration of 50-100 mg / mL.

12. The fluid delivery method according to claim 9, characterized in that, The preparation of the drug solution includes the addition of an antimicrobial preservative.

13. The fluid delivery method according to claim 9, characterized in that, The pivot point is split and removed to facilitate fluid delivery.

14. The fluid delivery method according to claim 9, characterized in that, The pivot point is sutured at one or more points to fix the pivot point to the skin.

15. The fluid delivery method according to claim 9, characterized in that, The bolus dose is administered by a medical professional.

16. The fluid delivery method according to claim 9, characterized in that, The bolus dose is administered periodically throughout the treatment.

17. The fluid delivery method according to claim 9, characterized in that, The bolus dose is administered by a medical professional.

Images