KR102065016B1 - Kit for pain reduction or healing of incision site after surgical operation - Google Patents

Abstract

The present invention relates to a kit for reducing or treating incisional pain. According to the present invention, a pain relief drug or a therapeutic drug is directly stabilized by injecting a pain-removing drug or a therapeutic drug in place immediately after incisional surgery in performing a surgical operation through an incision. And kits for reducing or treating incisional pain after surgery to enable effective treatment by sustained release.

Description

Kit for PAIN REDUCTION OR HEALING OF INCISION SITE AFTER SURGICAL OPERATION}

The present invention after surgery The present invention relates to a kit for reducing or treating incisional pain, and more particularly, in stabilization and sustained release by injecting a pain-removing drug or therapeutic drug into the surgical site immediately after incision surgery. A kit for reducing or treating incisional pain that allows effective treatment by release to In another aspect, the present invention includes a kit for reducing or treating incision pain, etc., in which there is no fear of precipitation when mixed with the drug and the drug is stably sustained-released.

During surgery, the incision site is injected with pain-removing drugs such as local anesthetics for the purpose of reducing pain after surgery, and drugs such as antibiotics and anti-inflammatory drugs are injected for treatment.

However, since most pain-relieving drugs are viscous solution and usually use the washing solution during the operation of the incision site, it is difficult to accurately and stably inject the pain-relieving drug into the incision site quickly and effectively. In addition, antibiotics and anti-inflammatory drugs are not effective because of their short half-life.

Accordingly, various wound dressings based on a temperature sensitive polymer based on body temperature have been developed, and the applicant of the present invention is also applying for a patent for wound dressing including a drug (Korean Patent No. 10-1125934).

However, it is necessary to use a variety of pain elimination or therapeutic drugs that can be changed depending on the size, condition or surgical progress of the surgical site, and if necessary, two or more types of mixtures may be used. It is not possible to manufacture the wound dressing included in the compounding ratio in advance, and even if it is manufactured in advance, it is not economically desirable to purchase various types, respectively, such as purchase cost and storage cost.

Therefore, the present invention is to solve the problems caused by the injection of the drug for the reduction or treatment of conventional surgical incision pain and to accurately and stably inject into the incision site surgical to enable the rapid and effective generation of the intended drug After surgery It is an object to provide a kit for reducing or treating incisional pain.

In another aspect, the present invention is to provide a kit for reducing or treating incision pain in which the drug is stable and sustained sustained release of the drug when mixed with the drug.

The above and other objects of the present invention can be achieved by the present invention described below.

In order to achieve the above object, as a kit for reducing or treating incision pain, a prefield syringe having a structure in which a non-crosslinkable thermosensitive viscous solution used as a stabilization matrix for pain elimination or therapeutic drug is filled and opened and closed through a stopper. Including the (300), wherein the non-crosslinkable temperature-sensitive viscous solution is a poly (ethylene oxide) / poly (propylene oxide) containing a poly (ethylene oxide) block and a poly (propylene oxide) block in a ratio of 90: 105 ~ 50: 70 ) / Poly (ethylene oxide) triblock copolymer containing at least 30% by weight and residual water for injection, with a viscosity of 50 to 5,000 cps at 5 ° C, 100,000 cps at 37 ° C and a rotatable rheometer at 5 ° C. Provided is a surgical kit, characterized in that the measured adhesion is 0.8 N or more. These surgical kits have no risk of precipitation when mixed with the drug, stably release the drug stably, and omit the crosslinking step, thereby simplifying the manufacturing process and providing economic advantages.

In addition, in the kit for reducing or treating pain in the incision site, the pre-filled syringe 300 is filled with a non-crosslinkable temperature-sensitive viscous solution used as a stabilization matrix of the pain relief or therapeutic drug and opened and closed through a stopper; And a mixed solution injection guide tube (100) for injecting a mixed solution containing a pain elimination or therapeutic drug and a non-crosslinkable temperature sensitive viscous solution in close proximity to the exposed incision site, wherein the non-crosslinkable temperature sensitive viscous solution includes 30% by weight or more of poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer containing poly (ethylene oxide) and poly (propylene oxide) blocks in a ratio of 90: 105 to 50:70 And a residual amount of water for injection, having a viscosity of 50 to 5,000 cps at 5 ° C., 100,000 cps at 37 ° C., and an adhesive force of 0.8 N or more as measured by a rotatable rheometer at 5 ° C., wherein the pain relief or therapeutic drug is used. Is an aqueous drug solution, wherein the non-crosslinkable temperature sensitive viscous solution and the drug aqueous solution have a volume ratio of 1: 0.5 to 40 (drug solution: non-crosslinkable temperature sensitive viscous solution). Provide an oversurgery kit. These surgical kits also have the risk of precipitation when mixed with the drug and not only stably release the drug stably but also eliminate the crosslinking step, thereby simplifying the manufacturing process and providing economic advantages.

In addition, as a method of using a kit for reducing or treating incisional pain, the needle is fastened to the first syringe 200, and then the needle is inserted into the pain removal or therapeutic drug to be used during surgery, and the drug is filled up to the indicator line of the first syringe. Then disconnecting the connected needle; Removing the stopper of the pre-filled syringe 300 which is pre-filled with a non-crosslinkable temperature-sensitive viscous solution and provided with a straw; Connecting the prefilled syringe from which the stopper is removed to one side of the syringe connector 400; Connecting the first syringe filled with the drug and the needle separated from the other side of a syringe tube; Mixing the drug with a non-crosslinkable thermosensitive viscous solution in a prefield syringe using a piston of a prefilled syringe and a first syringe communicating with a syringe tube; And separating the pre-filled syringe filled with the mixed solution from the syringe connector after the mixing, and injecting the mixed solution into the surgical incision, wherein the non-crosslinkable thermosensitive viscous solution is poly (ethylene oxide). At least 30% by weight of poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer containing a block and a poly (propylene oxide) block in a ratio of 90: 105 to 50:70 and remaining water for injection It includes, the viscosity is 50 ~ 5,000 cps at 5 ℃, 100,000 cps at 37 ℃ and the adhesion measured by a rotatable rheometer at 5 ℃ is more than 0.8 N, the pain relief or therapeutic drug is an aqueous drug solution, The non-crosslinkable temperature sensitive viscous solution and the drug aqueous solution of the surgical kit, characterized in that the volume ratio of 1: 0.5 ~ 40 (drug solution: non-crosslinkable temperature sensitive viscous solution) There is provided a method for.

The step of injecting the mixed solution to the surgical incision and applying is, for example, after the mixing, the prefilled syringe filled with the mixed solution in the syringe connecting tube, and the mixed solution injection guide tube or needle is inserted into the prefield syringe. The solution may be applied by injecting the surgical incision into the site.

In addition, as a kit for reducing or treating incision pain, a pre-filled syringe 300 having a structure in which a non-crosslinkable temperature sensitive viscous solution used as a stabilization matrix of a pain elimination or therapeutic drug is filled and opened and closed through a stopper; A mixed solution induction conduit (100) for injecting a mixed solution containing a pain elimination or therapeutic drug and a non-crosslinkable temperature sensitive viscous solution in proximity to the exposed incision site; A first syringe 200 for filling pain relief or therapeutic drugs immediately before use to prepare the mixed solution; A syringe connector 400 for mixing a substance filled in the first syringe and the prefield syringe, respectively; And a first syringe needle 201, wherein the non-crosslinkable temperature sensitive viscous solution is a solution having a viscosity at 5 ° C. of 50 to 5,000 cps and a viscosity at 37 ° C. of 100,000 cps or more. Provide surgical kits.

Crosslinking agent when the temperature-sensitive viscous solution in the surgical kit or surgical kit and its use method comprises more than 30% by weight of the triblock copolymer, for example 30 to 40% by weight; And / or Alginic acid or alginate; It is preferable that it is non-crosslinkable, More preferably, it is a crosslinking agent; Alginic acid; And alginate; non-crosslinkable, which does not include all, in this case, there is no fear of precipitation when mixed with the drug has the effect of stably sustained release of the drug.

As another example, the present invention is a kit for reducing or treating incision pain, the pre-filled syringe 300 is filled with a temperature-sensitive viscous solution that is used as a stabilization matrix of the pain relief or therapeutic drug and opened and closed through a stopper ; And a mixed solution injection guide tube (100) for injecting a mixed solution including a pain-removing or therapeutic drug and a temperature-sensitive viscous solution in close proximity to the exposed incision site.

The surgical kit, for example, the pre-filled syringe 300 is filled with a temperature-sensitive viscous solution used as a stabilization matrix of the pain relief or therapeutic drug and opened and closed through a stopper; and close to the exposed incision site A mixed solution injection induction tube (100) for removing pain or injecting a mixed solution mixed with a therapeutic drug and a temperature-sensitive viscous solution; and a first for filling pain relief or therapeutic drugs immediately before use to prepare the mixed solution; Syringe 200; And a syringe connector 400 for mixing a substance filled in the first syringe and the prefield syringe, respectively.

The surgical kit may further include, for example, the needle 201 for the first syringe.

The surgical kit may further include, for example, the needle 202 for the prefield syringe.

The temperature sensitive viscous solution may be, for example, a solution having a viscosity at 5 ° C. of 50 to 5,000 cps or 100 to 5,000 cps, and a viscosity at 37 ° C. of 100,000 cps or more.

The temperature sensitive viscous solution may be, for example, a non-pyrogenic viscous solution consisting of polyethylene-polypropylene-polyethylene polymer, alginic acid or sodium alginate, calcium chloride and water for injection.

In the present description, the non-pyrogenic viscous solution means that there is no exotherm when the phase is changed to Sol-Gel according to the temperature. It means below ° C.

The first syringe is, for example, the needle is pre-assembled or fastened immediately before use, it may be that the needle after the pain relief drug filling is separated.

The mixed solution injection guide tube may be used by being fastened to the prefield syringe so as to inject the mixed solution mixed in the prefield syringe into the incision site, for example.

The syringe connector may be, for example, an inner diameter, ie, an inner particle diameter of the tube through which the drug passes.

The surgical kit may further include, for example, absorbing means for absorbing and removing residual moisture around the incision.

As another example, the present invention is a method for using the surgical kit in the surgical incision, the needle is fastened to the first syringe and then inserted into the needle to the pain relief or therapeutic drug to be used during surgery and the drug to the indicator line of the first syringe Separating the connected needle after the filling; Removing the stopper of the prefilled syringe, which is pre-filled with a temperature sensitive viscous solution and provided with a straw; Connecting the stoppered prefield syringe to one side of the syringe connector; Connecting the first syringe filled with the drug and the needle separated from the other side of a syringe tube; Mixing the drug with a temperature sensitive viscous solution in a prefield syringe using a piston of a prefilled syringe and a first syringe communicating with a syringe tube; And separating the prefield syringe filled with the mixed solution from the syringe connector after the mixing, and inserting the mixed solution injection guide tube or the needle into the prefield syringe to inject and apply the mixed solution to the surgical incision site. It provides a method of using a surgical kit, characterized in that.

Before injecting the mixed solution into the surgical incision site may further comprise the step of sucking and removing the washing solution used during surgery using the suction suction.

The mixing ratio of the drug solution and the temperature sensitive viscous solution mixture mixed in the prefield syringe through the syringe connector may be, for example, 1: 0.5 to 40 (drug solution: temperature sensitive viscous solution) or 1: 0.5 to 5 in volume ratio. have.

In addition, the present invention provides a kit for reducing or treating pain in the incision site, the pre-filled syringe 300 is filled with a temperature-sensitive viscous solution used as a matrix for removing the pain or therapeutic drug and opened and closed through a stopper; And a mixed solution induction conduit (100) for injecting a mixed solution including a pain-reducing or therapeutic drug and a temperature-sensitive viscous solution in close proximity to the exposed incision site, wherein the temperature-sensitive viscous solution is poly (ethylene oxide). ) 20-40% by weight of poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer and residual amount of poly (propylene oxide) block in a ratio of 90: 105-50: 70 It contains water for injection and has a viscosity of 50 to 5000 cps or 500 to 3000 cps at 5 ° C., at least 100,000 cps or 100,000 to 2,000,000 cps at 37 ° C., and an adhesion of 0.8 N or more at 5 ° C. The pain relief or therapeutic drug is an aqueous drug solution, wherein the temperature sensitive viscous solution and the drug aqueous solution have a volume ratio of 1: 0.5 to 40 (drug solution: temperature sensitive viscous solution) or 1: 0.5 to 5, Provides a surgical kit.

In addition, the present invention is a method of using a kit for reducing or treating pain in the incision, the needle is fastened to the first syringe 200, and then inserted into the needle to the pain removal or therapeutic drug to be used in the surgery to the indicator line of the first syringe Separating the connected needle after filling the drug; Removing the stopper of the pre-filled syringe 300, which is pre-filled with a temperature-sensitive viscous solution and provided with a straw; Connecting the prefilled syringe from which the stopper is removed to one side of the syringe connector 400; Connecting the first syringe filled with the drug and the needle separated from the other side of a syringe tube; Mixing the drug with a temperature sensitive viscous solution in a prefield syringe using a piston of a prefilled syringe and a first syringe communicating with a syringe tube; And separating the pre-filled syringe filled with the mixed solution from the syringe connector after the mixing, and inserting the mixed solution injection guide tube or the needle into the pre-field syringe and injecting the mixed solution into the surgical incision and applying the mixed solution. , The temperature-sensitive viscous solution is a poly (ethylene oxide) / poly (propylene oxide) block poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) tree containing a ratio of 90: 105 ~ 50:70 20 to 40% by weight of block copolymer and residual water for injection, with a viscosity of 50 to 5000 cps or 500 to 3000 cps at 5 ° C., at least 100,000 cps or 100,000 to 2,000,000 cps at 37 ° C., rotatable at 5 ° C. Adhesion measured by rheometer is 0.8 N or more, the pain relief or therapeutic drug is a drug aqueous solution, the temperature-sensitive viscous solution and the drug aqueous solution volume ratio of 1: 0.5 ~ 40 (drug Aqueous solution: temperature sensitive viscous solution) or 1: 0.5 ~ 5 provides a method of using a surgical kit.

In addition, the present invention provides a kit for reducing or treating pain in the incision site, the pre-filled syringe 300 is filled with a temperature-sensitive viscous solution used as a matrix for removing the pain or therapeutic drug and opened and closed through a stopper; A mixed solution induction conduit (100) for injecting a mixed solution including a pain-reducing or therapeutic drug and a temperature-sensitive viscous solution in proximity to the exposed incision site; A first syringe 200 for filling pain relief or therapeutic drugs immediately before use to prepare the mixed solution; A syringe connector 400 for mixing a substance filled in the first syringe and the prefield syringe, respectively; And a first syringe needle 201, wherein the temperature-sensitive viscous solution includes a poly (ethylene oxide) block and a poly (propylene oxide) block in a ratio of 90: 105 to 50:70. 20-40% by weight of poly (propylene oxide) / poly (ethylene oxide) triblock copolymer, 0.005 ~ 0.1% by weight of CaCl ₂ as crosslinking agent, 0.05-3% by weight of alginic acid or sodium alginate and water for injection, 50 to 5000 cps or 500 to 3000 cps at 5 ° C., 100,000 cps or more at 100,000 ° C. or 100,000 to 2,000,000 cps at 37 ° C., and adhesion at 0.8 ° C. or higher at 0.8 ° C. The therapeutic drug is an aqueous solution of drug. , The temperature-sensitive viscous solution and the drug aqueous solution provides a surgical kit, characterized in that the volume ratio of 1: 0.5 ~ 40 (drug solution: temperature sensitive viscous solution) or 1: 0.5 ~ 2.

In addition, the present invention is a method of using the surgical kit for the surgical incision, the first syringe needle to the first syringe after inserting the needle to the pain relief or therapeutic drug to be used during surgery to the indication line of the first syringe Separating the connected needle after filling the drug; Removing the stopper of the prefilled syringe, which is pre-filled with a temperature sensitive viscous solution and provided with a straw; Connecting the stoppered prefield syringe to one side of the syringe connector; Connecting the first syringe filled with the drug and the needle separated from the other side of a syringe tube; Mixing the drug with a temperature sensitive viscous solution in a prefield syringe using a piston of a prefilled syringe and a first syringe communicating with a syringe tube; And separating the prefilled syringe filled with the mixed solution from the syringe connector after the mixing, and inserting the mixed solution injection guide tube or the prefield syringe needle into the prefield syringe to inject the mixed solution into the surgical incision and apply the mixed solution. Including, the temperature-sensitive viscous solution is a poly (ethylene oxide) block and poly (propylene oxide) block poly (ethylene oxide) / poly (propylene oxide) / poly (containing a ratio of 90: 105 ~ 50: 70 Ethylene oxide) 20-40% by weight of triblock copolymer, CaCl ₂ as crosslinking agent, 0.005 ~ 0.1% by weight, 0.05-3% by weight of alginic acid or sodium alginate and water for injection, the viscosity is 50-5000 cps or 500 at 5 ° C. ~ 3000 cps, 100,000 ~ 2,000,000 cps at 37 ℃, the adhesion measured by a rotatable rheometer at 5 ℃ more than 0.8 N, the therapeutic drug is a drug aqueous solution, the temperature sensitive viscosity And the drug solution has a volume ratio of 1: provides the use of a surgical kit, characterized in that 0.5-2 manner: 0.5 to 40 (drug solution: the temperature responsive viscous solution) or 1.

The alginate may be, for example, a metal alginate, preferably an alkali metal alginate or an alkaline earth metal alginate, most preferably an alkali metal alginate.

In the present invention having the above-described configuration, the pain-removing drug or the therapeutic drug that is needed immediately after the incision surgery can be mixed with the temperature-sensitive viscous solution in a simple operation in the surgical operation through the incision. Surgical kits can be provided for post-surgical pain reduction (pain / pain relief) and treatment that allow effective treatment by stabilizing and sustained release by infusion. In another aspect, the present invention can provide a kit for reducing or treating the pain of the incision site where there is no fear of precipitation when mixed with the drug and the drug is stably sustained release.

1 is a photograph showing the overall configuration of a kit for reducing and treating incisional pain in accordance with the present invention.
Figure 2 is a schematic diagram showing an embodiment according to the change over time using an assembly of the surgical kit of the present invention.
Figure 3 is a graph showing the measurement results of the stability test (A) of the temperature-sensitive viscous solution contained in the pain relief drug mixture solution of the present invention over time.
Figure 4 is a graph showing the measurement results of the sustained release test of the pain relief drug in the pain relief drug mixture solution of the present invention over time.
5 is a non-use of the pain-relieving drug and the temperature-sensitive viscous solution in the rat plantar pain-induced model using the surgical kit of the present invention, the sole use of the pain-relieving drug, the use of the temperature-sensitive viscous solution alone, pain relief drug mixture A graph showing the effects of each analgesia / analgesia over time using the solution.
Figure 6 is a graph showing the measurement results of the stability test according to the cross-linking of the temperature-sensitive viscous solution (containing 30% by weight of the temperature-sensitive polymer) contained in the pain relief drug mixture solution of the present invention over time.
Figure 7 is a photograph showing the precipitation test results of the pain relief drug mixture solution (left) and the treatment drug mixture solution (right) according to an embodiment of the present invention.
Figure 8 is a graph showing the measurement results of the sustained-release test of the pain-relieving drug (ibuprofen) of the pain-relieving drug mixed solution according to an embodiment of the present invention over time.
9 and 10 are the measurement of the sustained release test when the drug (ropivacaine vs bupivacaine) and the viscous solution (crosslinkability vs. non-crosslinking) in the pain-relieving drug mixture solution according to an embodiment of the present invention Graph showing results over time.

The present invention relates to a kit for reducing or treating incisional pain, comprising: a pre-filled syringe having a structure filled with a temperature-sensitive viscous solution used as a stabilization matrix of a pain elimination or therapeutic drug and opening and closing through a stopper; And a mixed solution injection guide tube for injecting a mixed solution containing the drug and a temperature sensitive viscous solution in close proximity to the exposed incision site.

In addition, the present invention is a kit for reducing pain in the incision site, a mixed solution induction pipe for injecting a pain-removing drug mixture solution in close proximity to the exposed incision site; and to prepare the pain relief drug mixture solution immediately before use A prefilled syringe having a structure in which a temperature-sensitive viscous solution used as a stabilization matrix of the pain relief or therapeutic drug mixture solution is filled and opened and closed through a stopper; And a syringe connector having opening and closing means for mixing the respective substances filled in the first and prefield syringes.

In addition, the present invention is a method for using the above-described surgical kit in the surgical incision site, unpacking the surgical kit in a sterile place, fastening the needle to the first syringe provided with a straw, such as a local anesthetic to be used during surgery Inserting a needle into the pain relief drug and filling the pain relief drug to the indicator line of the first syringe; A second step of separating the needle connected to the first syringe filled with the pain-relieving drug and removing the stopper of the pre-filled syringe, which is pre-filled with a temperature-sensitive viscous solution and provided with a straw; Connecting a syringe tube to the prefilled syringe from which the stopper is removed, and connecting the first syringe filled with the pain-relieving drug; A fourth step of uniformly mixing the pain-relieving drug with the temperature-sensitive viscous solution in the prefield syringe while pushing the rods of the first syringe and the prefield syringe connected to each other to the syringe connector from side to side; And a fifth step of separating the syringe connection tube and connecting the mixed solution injection induction tube to the prefield syringe to sufficiently inject and apply the pain relief material mixed solution to the surgical incision site.

In the present description, the temperature-sensitive viscous solution is meant to include both cross-linkable temperature-sensitive viscous solution and non-crosslinkable temperature-sensitive viscous solution unless otherwise stated.

Hereinafter, with reference to the accompanying drawings a preferred embodiment of the kit 10 for reducing incision pain in accordance with the present invention will be described in detail. The present invention is not limited to the embodiments disclosed below, but can be implemented in various different forms, only this embodiment is to make the disclosure of the present invention complete and to those skilled in the art to fully know the scope of the invention It is provided to give.

Figure 1 shows a kit 10 (hereinafter referred to as "surgical kit of the present invention") for reducing incision pain in accordance with the present invention.

As shown in Figure 1, the surgical kit 10 of the present invention is a mixed solution injection guide tube 100, the first syringe 200, pre-filled syringe 300, syringe connector 400 and needle 201, 202).

Here, all the components included in the surgical kit 10 of the present invention are to access the incision site of a variety of surgical operations, and thus configured to be applied directly in place on the incision site after surgery.

The mixed solution induction guide tube 100 is for injecting a pain-removing drug mixed solution in close proximity to the incision site exposed during the surgical operation, and has a conduit form with open ends at both ends made of a material such as Teflon. It can be used, for example, Teflon microconduit (capillary) can be used.

One end of the mixed solution injection guide tube 100 may be inserted into the prefield syringe inlet, and the mixed solution may be discharged or injected into the other end.

The mixed solution injection guide tube 100 is, for example, the total length is 60 to 70 mm, preferably 70 ± 3.5 mm, the outer diameter is 1.6 to 1.8 mm, preferably 1.7 ± 0.085 mm, the inner diameter is 1.1 to 1.4 mm, Preferably it is 1.26 ± 0.085 mm, it is easy to handle and use within this range, and the effect of appropriately distributing the drug to the surgical site is great.

The first syringe 200 is for filling a pain-relieving drug (not shown) immediately before use to prepare the pain-relieving drug mixture solution, and the needle 201 is pre-assembled, or just before use 201 It can be used by fastening to the first syringe 200, and after filling the first syringe 200 with a pain-removing drug (not shown) to separate the needle 201. The first syringe 200 is preferably applied if it is a commercially available product equipped with a piston.

The pain-relieving drug may be a local anesthetic, opiate analgesic, non-steroidal drug for the purpose of controlling acute pain after surgery, and for example, relatively safe lopivacaine hydrochloride, ibuprofen and the like.

The therapeutic drug is not particularly limited as long as it is dissolved in water and stable in an aqueous solution and can be used as an injection. For example, the therapeutic drug may be gentamicin, ibuprofen, or the like.

The present invention may comprise a drug and / or an aqueous solution of drug in a configuration.

In the present description, if the drug is intended for both pain relief and treatment, it may be classified as either a pain relief drug or a therapeutic drug.

The prefield syringe 300 generally has a structure of opening and closing with a stopper 301 instead of a needle to be fastened.

As a specific example, the pre-filled syringe 300 has a structure that is filled with a temperature-sensitive viscous solution 302 used as a substrate of the pain-relieving drug mixed solution and opened and closed through a stopper, and is stable to autoclaving.

The reason why the temperature-sensitive viscous solution is pre-filled is because it prevents the user's mistake that may occur during the filling process and reduces convenience and product manufacturing time in the operating room.

Here, the temperature-sensitive viscous solution 302 is a substrate that plays an important role for providing stability and sustained release by changing to a gel state by the body temperature after application to the surgical incision site, ion-crosslinked alginate and temperature sensitive It is composed of poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer and has a viscosity of 100 to 5,000 cps at 5 ° C, and a small amount of copolymer having a viscosity of 100,000 cps or more at 37 ° C. to that of the formulation in water for injection and CaCl ₂ it is preferred.

The ionic crosslinked alginate in the present description may mean that alginic acid or alginate is crosslinked by a crosslinking agent such as CaCl ₂ .

Viscosity (cps) in the present description follows the method of rotational viscometer method of the Korean Pharmacopoeia 2 method, Brookfield viscometer can be measured under the condition of # 4 spindle at 5 ℃, # 7 spindle at 37 ℃,

The temperature-sensitive viscous solution 302 is, for example, a pain such as a local anesthetic for controlling acute pain after surgery at a viscosity of 50 to 5,000 cps, 100 to 5,000 cps, or 500 to 3,000 cps, preferably 500 to 1,000 cps at 5 ° C. It is easy to mix with the removal material and gels in vivo at a viscosity of 100,000 cps or higher at 37 ° C, or 100,000 to 2,000,000 cps, preferably 500,000 to 2,000,000 cps, so that the pain-relieving drug can be stably Will be released.

As another example, the temperature-sensitive viscous solution 302 has a viscosity of 50 to 3,000 cps, or 100 to 2,000 cps, preferably 100 to 1,000 cps at 5 ° C. and a pain-removing substance such as a local anesthetic for controlling acute pain after surgery. It is easy to mix and gels in vivo at a viscosity of 100,000 cps or more, or 100,000 to 5,000,000 cps, preferably 1,000,000 to 4,000,000 cps at 37 ° C, thereby stably releasing pain-relieving drug to the application site. .

The temperature sensitive viscous solution 302 may include, for example, 0.05 to 3% by weight, or 0.1 to 3% by weight, preferably 0.1 to 2% by weight, of the ion-crosslinked alginate in 100% by weight of the solution. It can provide the effect of improving the stability of the temperature-sensitive viscous solution.

The weight of the ion-crosslinked alginate herein is not particularly limited when it is understood in the art as the weight of the ion-crosslinked alginate, but, for example, a crosslinking agent corresponding to 10% of the weight of alginic acid and / or alginate to be added. It can mean the sum of the weight of the weight.

Examples of the crosslinking agent of the ion-crosslinked alginate include Li ⁺ , Na ⁺ , K ⁺ , Rb ⁺ , Cs ⁺ , Fr ⁺ , Be ²⁺ , Ra ²⁺ , B ³⁺ , Al ³⁺ , Ga ²⁺ , Mg ² Halides having at least one cation selected from ⁺ , Ca ²⁺ , Sr ²⁺ , Ba ²⁺ , preferably at least one cation selected from Mg ²⁺ , Ca ²⁺ , Sr ²⁺ , Ba ²⁺ , or chitosan One or more selected from glutaaldehyde, formalin and polylysine may be used, but is not specific thereto.

The temperature-sensitive viscous solution 302 is, for example, 20-40% by weight of 100% by weight of the solution of the temperature-sensitive poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer, or crosslinking It can be included in the range of 20 to 30% by weight or 30 to 40% by weight, in this range can provide an effect that the drug for pain removal is stable in the body.

Poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymers include poly (ethylene oxide) blocks and poly (propylene oxide) blocks, for example, in a ratio of 90: 105 to 50:70. It can be used, in this range can provide the effect of maintaining the pain-relieving drug in the body.

Other properties such as the weight average molecular weight of the poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer is poly (ethylene oxide) / poly commonly used in the art of temperature-sensitive viscous solution It does not restrict | limit especially if it corresponds to the range of a (propylene oxide) / poly (ethylene oxide) triblock copolymer.

The temperature-sensitive viscous solution 302 may include, for example, CaCl ₂ in a range of 0.005 to 0.1% by weight or 0.007 to 0.1% by weight, preferably 0.01 to 0.1% by weight, in 100% by weight of the solution. Alginic acid or alginate may provide the effect of homogeneously mixing with the poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer.

As another example, the temperature-sensitive viscous solution 302 may include CaCl ₂ in a range of 0.005 to 0.3% by weight or 0.01 to 0.3% by weight, preferably 0.01 to 0.2% by weight, in 100% by weight of the solution. The crosslinked alginic acid or alginate may provide the effect of homogeneously mixing with the poly (ethylene oxide) / poly (propylene oxide) / poly (ethylene oxide) triblock copolymer.

The temperature-sensitive viscous solution 302 may have an adhesive force of 0.8 N or more, or 0.8 N to 5 N, for example, measured using a rotary viscometer. Within this range, the pain-relieving drug may be stably maintained in the body. Can provide.

Adhesion force (N) in the present substrate can be measured under 5 ° C conditions using a rotatable rheometer.

The temperature-sensitive viscous solution 302 is biocompatible to avoid problems such as a slow recovery rate at the surgical incision or a decrease in the adhesive strength of the seal stitched to the surgical incision, and the healing of the surgical incision is normally healed. It is preferable to have.

The syringe connector 400 is for ejecting and mixing the respective substances filled in the first and prefield syringes, and the inner diameter is 12 mm or less, 10 mm or less, 1 to 10 mm, so that the viscous solution can move smoothly. Or 1.9 to 4.1 mm. The mixing ratio of the pain-relieving substance (drug) or therapeutic substance (drug) and the temperature sensitive viscous solution mixture mixed in the prefield syringe via the syringe connector is, for example, 1: 0.5 to 5 (drug solution: temperature sensitive viscous solution) It may be in a volume ratio of 1: 0.5 to 3, or a volume ratio of 1: 0.5 to 2, and may provide an effect of stably maintaining the pain-removing drug or therapeutic drug in the body within this range.

As another example, when the pH of the aqueous drug solution is 4 or more or 4 to 8, the volume ratio of the temperature-sensitive viscous solution and the drug may be 1: 0.5-5 (drug solution: temperature-sensitive viscous solution) or 1: 0.5-4, If the pH is less than 4 or more than 1 to less than 4, it may be 1: 4-40 (drug solution: thermosensitive viscous solution) or 1: 5-40, and within this range pain relief drugs or therapeutic drugs It is not released, but remains stable to release the sustained release effect.

The volume of the aqueous drug solution in the present description may be replaced with the volume of water minus the drug, depending on the convenience of measurement or treatment, as will be apparent to those skilled in the art.

In the present description, the concentration of the final drug mixture in which the aqueous drug solution and the temperature-sensitive viscous solution are mixed is not particularly limited, but is, for example, 0.1 to 1.5% by weight, 0.1 to 0.1% by weight, 0.2 to 0.8% by weight, 0.1 to 0.5% by weight or 0.2 to 0.4% by weight.

The syringe connector 400 is separated from the prefilled syringe 300 filled with the mixture through the syringe connector 400, and then the stopper of the mixed pain relief drug mixture solution (not shown) in the prefield syringe 300 ( 301) By fastening the above-described mixed solution injection guide tube 100 or the second needle 202 to the fastening site, the pain-removing drug mixed solution can be stably injected into the desired surgical incision. Through the stable injection in such a precise site is changed to a gel state by the temperature-sensitive viscous solution 302 contained in the pain relief drug mixture solution to release the pain relief drug slowly. For example, the change to the gel state is to maintain its shape stably after about 5 minutes.

And, if necessary, it is also possible to absorb and remove the residual moisture around the incision site by using a separate absorbing means (not shown), for example, cotton swabs, gauze.

Looking at the method of using the surgical kit 10 of the present invention in the surgical incision with reference to the drawings as follows.

Figure 2 is a schematic diagram showing an embodiment using a surgical kit of the present invention in accordance with changes over time.

Referring to FIG. 2, as a step S1, the package of the surgical kit 10 is unpacked at a sterilized place, and the needle 201 is fastened to the first syringe 200 provided with a straw. Then, the needle 201 is inserted into the pain-removing drug such as a local anesthetic to be used during surgery, and the pain-removing drug is filled up to the indicator line of the first syringe 200.

Step S2 is composed of a total of three steps of step S2-1, step S2-2, step S2-3. First, in step S2-1, the needle 201 connected to the first syringe 200 filled with the pain-removing drug is separated (see left), and the product-dye sold by the present applicant as the temperature-sensitive viscous solution 302 is marketed. Remove the stopper 301 of the prefilled syringe 300, which is prefilled with K gel (KFDA No. 09-826) and provided with a straw (see right).

In step S2-2, the syringe connector 400 is connected to the prefield syringe 300 from which the stopper 301 is removed, and the first syringe 200 filled with the pain-removing drug is connected. Be careful not to spill the pain-relieving drug.

In step S2-3, the pain-removing drug and the temperature-sensitive viscous solution in the prefield syringe 300 are pushed to the left and right push rods of the first syringe 200 and the prefield syringe 300 connected to each other by the syringe connector 400 Mix evenly.

Subsequently, as a step S3, the syringe connector 400 is disconnected, and then the mixed solution injection induction tube 100 or the second needle 202 is connected to the prefield syringe 300 to connect the pain-removing substance mixed solution to the surgical incision site. Inject enough to apply.

If necessary, it may include a step of sucking and removing the washing solution used in the surgery prior to the step S1 by suction suction (not shown) and confirming that sufficient hemostasis is made on the wound surface during the operation.

The stability test of the temperature-sensitive viscous solution of the present invention and the results of the release test of the pain-relieving drug in the temperature-sensitive viscous solution and the pain-relieving drug mixture are shown in FIGS. 3 and 4.

Briefly summarized the test results, as shown in Figure 3 showing the results of the in vitro stability test of the temperature-sensitive viscous solution, when used in a temperature-sensitive viscous solution compared to the temperature-sensitive polymer alone, the stability is maintained up to 7 days As shown in FIG. 4, which shows the results of the release test of the pain relief drug mixture, it was confirmed that the pain relief drug was released slowly up to 3 days (72 hours).

By using the surgical kit (10) of the present invention in the rat plantar pain induction model, the pain elimination drug and the use of the temperature-sensitive viscous solution, the use of the pain-removing drug alone, the use of the temperature-sensitive viscous solution alone, pain relief drug mixture Each analgesic / analgesic effect with the use of the solution is shown in FIG. 5.

The non-use of pain-relieving drug and temperature-sensitive viscous solution is indicated as Control, the use of temperature-sensitive viscous solution alone is indicated as DDK, and the use of pain-relieving drug alone is abbreviated Ropi. (% By weight in aqueous solution concentration) was written, and the use of the pain-relieving drug mixed solution was written as DDK / Ropi.

In the present description, the concentration% means the weight% concentration unless otherwise stated.

For reference, Ropi. 0.25% refers to a composition in which the temperature sensitive viscous solution (viscous solution) and the pain-relieving drug are mixed with ropivacaine hydrochloride (drug solution) in a volume ratio of 2: 1, and the final drug concentration is 0.25% by weight. do.

To summarize the test results, it was confirmed that the test group using the pain-relieving drug mixture solution effectively reduced the pain compared to the test group using the pain-relieving drug alone.

Therefore, according to the above evaluation results, it can be seen that the pain-relieving drug mixture solution injected by the surgical kit of the present invention is very effective in providing stabilization and sustained release effect on the surgical incision, in particular, pain-relieving drug mixture It can be confirmed that it is preferable from an economic point of view that the solution can be stably prepared whenever necessary by a simple operation.

[Additional Test Results]

The measurement results of the stability test according to the crosslinking of the temperature-sensitive viscous solution (containing 30% by weight of the temperature-sensitive polymer) contained in the pain-relieving drug or the therapeutic drug mixture solution of the present invention is shown in FIG. In the test results, when the temperature-sensitive polymer content is 25% by weight or less (not shown), the stability of the cross-linked temperature-sensitive viscous solution is considerably higher than that of the uncrosslinked temperature-sensitive viscous solution, but the temperature-sensitive polymer content is 30% by weight. When it is more than% (see Fig. 6), the stability of both the cross-linked viscous solution and the non-cross-linked viscous solution is maintained for up to 7 days it is confirmed that almost no difference.

The precipitation test results of the pain relief drug mixture solution (left) and the therapeutic drug mixture solution (right) containing the crosslinked temperature-sensitive viscous solution according to an embodiment of the present invention are shown in FIG. 7. Here, DDK Gel refers to a gel consisting of alginate crosslinked with Poloxamer. In the test results, in the case of the pain-relieving drug mixture solution, ibuprofen used as the pain-relieving drug reacts with CaCl ₂ , a crosslinking agent, to form a precipitate, and in the case of the therapeutic drug mixture solution, gentamicin used as the therapeutic drug. It was confirmed that the pH of the solution was lowered to precipitate sodium alginate. That is, no precipitation occurred when the pain-relieving or therapeutic drug mixture did not contain the crosslinking agent CaCl ₂ or alginate.

8 shows the measurement results of the sustained release test of the pain-relieving drug (ibuprofen) of the pain-relieving drug mixed solution according to one embodiment of the present invention. The sustained release test was conducted by mixing an aqueous solution of ibuprofen with a 30% by weight solution of poloxamer containing no crosslinked alginate in a volume ratio of 2: 1. In describing the test results, it was confirmed that the drug was slowly released until 3 days (72 hours) in all the pain-relieving drug mixture solution.

Measurement results of the sustained release test at the time of different types of drugs (ropibakane vs. bulk bakane) and viscous solution (crosslinkability vs. noncrosslinking) of the pain relief drug mixture solution according to an embodiment of the present invention 9 and 10. The sustained release test was conducted by mixing a 0.75% by weight aqueous drug solution with a temperature-sensitive viscous solution (crosslinked alginate and 30% by weight DDK gel vs. poloxamer 30% by weight solution containing poroxamer) in a volume ratio of 2: 1. In describing the test results at this time, the pain-relieving drug mixed solution according to the present invention is not significantly affected by the type of drug or crosslinking of the temperature-sensitive viscous solution, and all drugs are released slowly until 3 days (72 hours). It was confirmed.

In the present description, the crosslinkability means a case containing a crosslinking agent or a crosslinked alginate, and the noncrosslinking means a case not including a crosslinking agent or a crosslinked alginate.

As described above with reference to the drawings illustrated for the kit for reducing the incision pain in accordance with the present invention, the present invention is not limited by the embodiments and drawings disclosed herein, the technical spirit of the present invention Of course, various modifications may be made by those skilled in the art within the scope.

10: surgical kit 100: mixed solution induction pipe
200: first syringe 201: first needle 202: second needle
300: pre-filled syringe 301: stopper 302: temperature sensitive viscous solution
400: syringe connector with opening and closing means

Claims (15)

A kit for reducing or treating incisional pain, comprising a pre-filled syringe 300 having a structure in which a non-crosslinkable thermosensitive viscous solution used as a stabilization matrix for pain relief or treatment is filled and opened and closed through a stopper.
The non-crosslinkable temperature sensitive viscous solution is a poly (ethylene oxide) / poly (propylene oxide) / poly (propylene oxide) / poly (ethylene oxide) containing a poly (ethylene oxide) block and a poly (propylene oxide) block in a ratio of 90: 105 ~ 50:70 Triblock copolymer containing at least 30% by weight and the remaining water for injection, the viscosity is 50 ~ 5,000 cps at 5 ℃, at least 100,000 cps at 37 ℃ and the adhesive strength of 0.8 N or more measured by a rotatable rheometer at 5 ℃ Surgical operation kit, characterized in that. The method of claim 1,
The surgical kit includes a mixed solution induction conduit (100) for injecting a mixed solution of pain relief or therapeutic drug and the non-crosslinkable temperature sensitive viscous solution in proximity to the exposed incision site; and includes the pain The removing or treating drug is an aqueous drug solution, and the non-crosslinkable thermosensitive viscous solution and the drug aqueous solution have a volume ratio of 1: 0.5 to 40 (drug solution: non-crosslinkable thermosensitive viscous solution). The method of claim 1,
The surgical kit,
A pre-filled syringe 300 having a structure in which a non-crosslinkable temperature sensitive viscous solution used as a stabilization matrix of the pain elimination or therapeutic drug is opened and closed through a stopper; and a pain elimination or therapeutic drug in proximity to the exposed incision site And a mixed solution induction conduit (100) for injecting a mixed solution mixed with a non-crosslinkable temperature-sensitive viscous solution; and a first syringe (200) for filling pain relief or therapeutic drugs immediately before use to prepare the mixed solution. ; And a syringe connector (400) for mixing the substances filled in the first syringe and the prefield syringe, respectively. The method of claim 3,
The surgical kit further comprises a first needle for the syringe 201. The method of claim 1,
The surgical kit further comprises a needle for the pre-filled syringe (202). The method of claim 2,
When the pH of the aqueous drug solution is 4 or more, the volume ratio of the non-crosslinkable temperature-sensitive viscous solution and the aqueous drug solution is 1: 0.5-5 (drug solution: non-crosslinkable temperature-sensitive viscous solution), and when the pH of the aqueous drug solution is less than 4 The volume ratio of the temperature-sensitive viscous solution and the aqueous drug solution is 1: 4 to 40 (drug solution: non-crosslinkable temperature-sensitive viscous solution), the surgical surgery kit. The method of claim 3,
The first syringe is a needle is pre-assembled or fastened immediately before use, the surgical kit, characterized in that the needle is removed after pain removal or filling the therapeutic drug. The method of claim 2,
The mixed solution injection induction pipe, the surgical kit, characterized in that is used to be fastened to the prefield syringe to inject the mixed solution mixed in the prefield syringe to the incision site. The method of claim 3,
The syringe connector is a surgical kit, characterized in that the inner diameter is 12 mm or less. The method of claim 1,
Surgical kit further comprises an absorbing means for absorbing and removing residual moisture around the incision. The method of claim 2,
The non-crosslinkable temperature sensitive viscous solution and the drug aqueous solution is a surgical kit, characterized in that the volume ratio 1: 2 ~ 5 (drug solution: non-crosslinkable temperature sensitive viscous solution). The method of claim 1,
The non-crosslinkable temperature sensitive viscous solution is a surgical kit, characterized in that containing 30 to 40% by weight of the triblock copolymer. delete delete A kit for reducing or treating incisional pain,
A pre-filled syringe 300 having a structure in which a non-crosslinkable temperature sensitive viscous solution used as a stabilization matrix for pain elimination or therapeutic drug is filled and opened and closed through a stopper;
A mixed solution induction conduit (100) for injecting a mixed solution containing a pain elimination or therapeutic drug and a non-crosslinkable temperature sensitive viscous solution in proximity to the exposed incision site;
A first syringe 200 for filling pain relief or therapeutic drugs immediately before use to prepare the mixed solution; A syringe connector 400 for mixing a substance filled in the first syringe and the prefield syringe, respectively; And a first syringe needle 201;
The non-crosslinkable temperature-sensitive viscous solution is a surgical kit, characterized in that the viscosity at 5 ℃ 50 ~ 5,000 cps, the solution at 37 ℃ viscosity of 100,000 cps or more.

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