Patent Description:
During a surgical procedure, an incision site is injected with a pain relief drug such as a local anesthetic for the purpose of relieving postoperative pain and is injected with drugs such as antibiotics and anti-inflammatory drugs for therapeutic purposes.

However, since most pain-relieving drugs are non-viscous solutions and a washing solution is usually used during incisional surgery, it is difficult to quickly and effectively produce the intended drug effect quickly and effectively by accurately and stably injecting the pain relief drug into a target incision site. In addition, the antibiotics and anti-inflammatory drugs are not effective due to their short half-life.

Accordingly, various wound dressings based on body temperature-responsive polymers have been developed, and the applicant of the present invention also has filed a patent application related to a drug-containing wound dressing (<CIT>).

<CIT> discloses a composition for the treatment of surgical incisions comprising: a drug, <NUM>-<NUM> wt% of poloxamer <NUM>, the composition has a viscosity at room temperature of from <NUM>,<NUM> to <NUM>,<NUM>,<NUM> mPa. The composition is applied through a syringe with a needle.

However, various pain relief drugs or treatment drugs may be required depending on the size or condition of an incision site or on the progress of surgery, and if necessary, a mixture of two or more thereof needs to be used. However, a wound dressing obtained by mixing all kinds of drugs together at various mixing ratios in view of this fact cannot be prepared in advance, and even if this wound dressing is prepared in advance, purchasing each of various kinds of drugs is economically undesirable in terms of purchase costs, storage costs, etc..

Therefore, it is an object of the present invention to provide a kit for treating or relieving postoperative incision site pain, which may overcome conventional problems occurring when injecting drugs for treating or relieving surgical incision site pain and may quickly and effectively produce the intended drug effect by accurately and stably injecting a drug into a target incision site.

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

To achieve the above object, the present invention provides a surgical kit as defined in claim <NUM>. a first syringe <NUM> configured to be filled with the pain relief or treatment drug immediately before use so as to prepare the mixture solution; and a syringe connector <NUM> configured to mix the substances filled in the first syringe and the prefilled syringe, respectively.

In one embodiment, the surgical kit may further include a syringe needle <NUM> for the first syringe.

In one embodiment, the surgical kit may further include a syringe needle <NUM> for the prefilled syringe.

In one embodiment, the temperature-responsive viscous solution may be a non-pyrogenic viscous solution including the polyethylene-polypropylene-polyethylene polymer, alginic acid sodium alginate, calcium chloride, and water for injection.

In the present description, the term "non-pyrogenic viscous solution" means that there is no heat generation during temperature-dependent so-gel phase transition. As a specific example, the term means that the temperature change during the phase transition is <NUM> or less, <NUM> or less, or <NUM> or less.

In one embodiment, the first syringe may be preassembled with a syringe needle or connected with the syringe needle immediately before use, and the syringe needle may be separated from the first syringe after being filled with the pain relief drug.

In one embodiment, the mixture solution injection guide tube may be connected to the prefilled syringe such that the mixture solution in the prefilled syringe may be injected into the incision site.

In one embodiment, the syringe connector may have an inner diameter of <NUM> or less, through which the drug passes.

In one embodiment, the surgical kit may further include an absorption means for absorbing and removing water remaining around the incision site.

The surgical kit according to the present invention can be used in a method including the steps of: connecting a syringe needle to a first syringe, inserting the syringe needle into the pain relief or treatment drug to be used during surgery, filling the drug into the first syringe up to a marked line, and then separating the connected syringe needle; removing a stopper from the prefilled syringe prefilled with the temperature-responsive viscous solution and equipped with a piston; connecting the prefilled syringe, from which the stopper was removed, to one side of a syringe connector; connecting the first syringe, which contains the drug filled therein and from which the syringe needle was separated, to the other side of the syringe connector; mixing the drug with the temperature-responsive viscous solution in the prefilled syringe by using the piston of each of the first syringe and the prefilled syringe, which communicate with each other by the syringe connector; and after the mixing, separating the prefilled syringe, filled with the mixture solution, from the syringe connector, inserting the mixture solution injection guide tube or a syringe needle into the prefilled syringe, and applying the mixture solution to the surgical incision site by injecting the mixture solution into the surgical incision site.

The method may further include, before injecting the mixture solution into the surgical incision site, a step of sucking and removing a washing solution used during the surgery by a suction means.

The surgical kit for use in treating or relieving incision site pain, may also include a first syringe <NUM> configured to be filled with the pain relief or treatment drug immediately before use so as to prepare the mixture solution; and a syringe connector <NUM> configured to mix the substances filled in the first syringe and the prefilled syringe, respectively, wherein the temperature-responsive viscous solution additionally includes <NUM> to <NUM> wt% of Cacl<NUM> as a crosslinking agent.

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

The present invention configured as described above may provide a kit for treating and reducing (relieving/killing) postoperative incision site pain, which makes it possible to mix a necessary pain relief drug or treatment drug with a temperature-responsive viscous solution by a simple procedure in situ after incisional surgery during an incisional surgical procedure, and makes effective treatment possible by injecting the drug-c containing mixture into a surgical site and stably and slowly releasing the drug.

The present invention provides a surgical kit for treating or relieving incision site pain as defined in claim <NUM>.

The kit for relieving incision site pain may also comprise: a first syringe configured to be filled with a pain relief drug immediately before use so as to prepare the pain relief drug-containing mixture solution; and a syringe connector configured to mix the substances filled in the first syringe and the prefilled syringe, respectively, the syringe connector having an opening/closing means.

Hereinafter, preferred embodiments of a kit <NUM> for alleviating incision site pain according to the present invention will be described in detail with reference to the accompanying drawings.

<FIG> illustrates a kit <NUM> for relieving incision site pain according to the present invention (hereinafter referred to as the surgical kit of the present invention").

As illustrated in <FIG>, the surgical kit <NUM> of the present invention includes a mixture solution injection guide tube <NUM>, a first syringe <NUM>, a prefilled syringe <NUM>, a syringe connector <NUM>, and syringe needles <NUM> and <NUM>.

Here, all the components included in the surgical kit <NUM> of the present invention may access incision sites during various surgical procedures, and thus are configured such that they may be applied to incision sites in situ after surgical operations.

The mixture solution injection guide tube <NUM> serves to inject a pain relief drug-containing mixture solution in close proximity to an exposed incision site during a surgical operation. It may be composed of a both-end-open type tube made of a flexible material such as Teflon. For example, it may be composed of a Teflon capillary tube.

The mixture solution injection guide tube <NUM> may be configured such that one end thereof may be inserted into the inlet of the prefilled syringe and the mixture solution may be discharged or injected through the other end.

The mixture solution injection guide tube <NUM> has, for example, a total length of <NUM> to <NUM>, preferably <NUM> ± <NUM>, an outer diameter of <NUM> to <NUM>, preferably <NUM> ± <NUM>, and an inner diameter of <NUM> to <NUM>, preferably <NUM> ± <NUM>. Within these ranges, the mixture solution injection guide tube is easy to handle and convenient to use, and the effect of appropriately distributing the drug in the surgical site is great.

The first syringe <NUM> is configured to be filled with a pain relief drug (not shown) immediately before use so as to prepare the pain relief drug-containing mixture solution. The first syringe <NUM> may be preassembled with a syringe needle <NUM> before use, or may be connected with the syringe needle <NUM> immediately before use. After the first syringe <NUM> is filled with a pain relief drug (not shown), the syringe needle <NUM> is separated therefrom. As the first syringe <NUM>, any commercially available product equipped with a piston is preferably used.

As the pain relief drug, a local anesthetic, an opiate analgesic, a nonsteroidal drug are used for the purpose of controlling postoperative acute pain. For example, ropivacaine hydrochloride, ibuprofen or the like may be used which is relatively safe.

The pain relief drug selected from a local anesthetic, an opiate analgesic, a nonsteroidal drug, is not particularly limited as long as it dissolves in water, is stable in an aqueous solution, and may be used as an injection. For example, it may be ibuprofen.

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

The prefilled syringe <NUM> preferably has a structure which is opened and closed by a stopper <NUM>, instead of a syringe needle which is generally connected.

As a specific example, the prefilled syringe <NUM> is filled with a temperature-responsive viscous solution <NUM> acting as a matrix for the pain relief drug-containing mixture solution, has a structure which is opened and closed by a stopper, and is stable to autoclaving.

Here, the reason why the temperature-responsive viscous solution is pre-filled is to prevent the user's mistakes from occurring during the filling process, provide convenience during use in an operating room, and shorten the product production time.

In this regard, the temperature-responsive viscous solution <NUM> is a matrix which is changed to a gel state by the body temperature after application to a surgical incision site and plays an important role in providing stability and sustained-release properties. The temperature-responsive viscous solution is composed of an ionically crosslinked alginate and a temperature-responsive poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer. It is preferably composed of a mixture further comprising a trace amount of CaCl<NUM>, and water for injection.

In the present description, the term "ionically crosslinked alginate" may refer to an alginic acid or alginate crosslinked by, for example, a crosslinking agent such as CaCl<NUM>.

In the present description, viscosity (cps) is measured with a Brookfield viscometer under conditions of #<NUM> spindle at <NUM> and #<NUM> spindle at <NUM> in accordance with method <NUM> (rotational viscometer method) described in the Korean Pharmacopoeia.

At <NUM>, the temperature-responsive viscous solution <NUM> has a viscosity of <NUM> to <NUM>,<NUM> cps (<NUM> cps corresponds to <NUM> mPA·s), <NUM> to <NUM>,<NUM> cps, or <NUM> to <NUM>,<NUM> cps, preferably <NUM> to <NUM>,<NUM> cps, and is easily mixed with a pain relief agent such as a local anesthetic for controlling postoperative acute pain. The temperature-responsive viscous solution is gelled in vivo, and allows the pain relief drug to be stably and slowly released to a target site.

As another example, at <NUM>, the temperature-responsive viscous solution <NUM> has a viscosity of <NUM> to <NUM>,<NUM> cps, or <NUM> to <NUM>,<NUM> cps, preferably <NUM> to <NUM>,<NUM> cps, and is easily mixed with a pain relief agent such as a local anesthetic for controlling postoperative acute pain.

The temperature-responsive viscous solution contains an ionically crosslinked alginate in an amount of <NUM> to <NUM> wt%, or <NUM> to <NUM> wt%, preferably <NUM> to <NUM> wt%, based on <NUM> wt% of the solution. Within this range, the effect of improving the stability of the temperature-responsive viscous solution may be provided.

A crosslinking agent for the ionically crosslinked alginate may be, for example, one or more selected from among a halide having one or more cations selected from among Li+, Na+, K+, Rb+, Cs+, Fr+, Be<NUM>+, Ra<NUM>+, B<NUM>-, Al<NUM>+, Ga<NUM>+, Mg<NUM>+, Ca<NUM>+, Sr<NUM>+ and Ba<NUM>+, preferably one or more cations selected from among Mg<NUM>+, Ca<NUM>+, Sr<NUM>+ and Ba<NUM>+, or chitosan, glutaraldehyde, formalin, and poly-L-lysine, but is not limited.

The temperature-responsive viscous solution <NUM> contains the temperature-responsive poly (ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer in an amount of <NUM> to <NUM> wt%. Within this range, the effect of stably maintaining the pain relief drug in vivo may be provided.

The poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer includes a poly(ethylene oxide) block and a poly(propylene oxide) block at a ratio of <NUM> : <NUM> to <NUM> : <NUM>. Within this range, the effect of stably maintaining the pain relief drug in vivo may be provided.

Other properties of the poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer, such as weight-average molecular weight, are not particularly limited as long as they correspond to the properties of poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymers which may generally be used in the technical field related to temperature-responsive viscous solutions.

The temperature-responsive viscous solution <NUM> may contain CaCl<NUM> in an amount of <NUM> to <NUM> wt% or <NUM> to <NUM> wt%, preferably <NUM> to <NUM> wt%, based on <NUM> wt% of the solution. Within this range, the effect of uniformly mixing the crosslinked alginate with the poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer may be provided.

As another example, the temperature-responsive viscous solution <NUM> may contain CaCl<NUM> in an amount of <NUM> to <NUM> wt% or <NUM> to <NUM> wt%, preferably <NUM> to <NUM> wt%, based on <NUM> wt% of the solution. Within this range, the effect of uniformly mixing the crosslinked alginate with the poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer may be provided.

The temperature-responsive viscous solution <NUM> has a stickiness of <NUM> N or higher, or <NUM> N to <NUM> N. Within this range, the effect of stably maintaining the pain relief drug in vivo may be provided. The stickiness (N) is measured using a rotational rheometer at <NUM>.

The temperature-responsive viscous solution <NUM> is biocompatible to avoid problems such as a slow recovery rate of a surgical incision site or a decrease in the adhesive strength of a suture suturing the incision site, and preferably has the property of allowing the surgical incision site to be normally healed.

The syringe connector <NUM> serves to discharge and mix the respective substances filled in the first and prefilled syringes, and preferably has an inner diameter of <NUM> or less, <NUM> or less, <NUM> to <NUM>, or <NUM> to <NUM>, so as to enable the viscous solution to smoothly move therein. The mixing ratio between the pain relief substance (drug) or the treatment substance (drug) and the temperature-responsive viscous solution, which are mixed and introduced into the prefilled syringe through the syringe connector, may be a volume ratio of <NUM>:<NUM> to <NUM> (aqueous drug solution : temperature-responsive viscous solution) or <NUM>:<NUM> to <NUM>. Within this range, the effect of stably maintaining the pain relief drug or the treatment drug in vivo may be provided. When the pH of the drug aqueous solution is <NUM> or more or <NUM> to <NUM>, the volume ratio between the temperature-responsive viscous solution and the drug is <NUM>:<NUM> to <NUM> (aqueous drug solution : temperature-responsive viscous solution), and when the pH is pH is less than <NUM> or <NUM> to <NUM>, the volume ratio is <NUM>:<NUM> to <NUM> (aqueous drug solution : temperature-responsive viscous solution). Within this range, the pain relief drug or the treatment drug is not released quickly in vivo, is stably maintained in vivo, and is slowly released.

In the embodiments according to the invention the concentration of a final drug mixture containing the aqueous drug solution and the temperature-responsive viscous solution is <NUM> to <NUM> wt%, or <NUM> to <NUM> wt%.

From the prefilled syringe <NUM> filled with the mixture through the syringe connector <NUM>, the syringe connector <NUM> is separated. Then, to the part connected with the stopper <NUM> for the pain relief drug-containing mixture solution (not shown) in the prefilled syringe <NUM>, the above-described mixture solution injection guide tube <NUM> or second syringe needle <NUM> is connected instead of the stopper, whereby the pain relief drug-containing mixture solution can be stably injected into a target surgical incision site. Through this accurate and stable injection of the mixture solution into the target incision site, the pain relief drug-containing mixture solution is changed to a gel state by the temperature-responsive viscous solution <NUM> contained therein and slowly releases the pain relief drug. For example, the gel state stably maintains its shape after about <NUM> minutes.

In addition, if necessary, it is also possible to absorb and remove water remaining around the incision site by using a separate absorbing means (not shown), for example, cotton swabs or gauze.

A method of using the surgical kit <NUM> of the present invention for a surgical incision site will now be described with reference to the accompanying drawings.

<FIG> is a schematic view showing an embodiment in which the surgical kit of the present invention is assembled and used, in a time-dependent manner.

Referring to <FIG>, in step S1, in a sterilized place, the package of the surgical kit <NUM> is removed, and the syringe needle <NUM> is connected to the first syringe <NUM> equipped with a piston. Then, the needle <NUM> is inserted into the pain relief drug such as a local anesthetic to be used during surgery, and the pain relief drug is filled into the first syringe <NUM> up to the marked line.

Step S2 consists of a total of three steps: step S2-<NUM>, step S2-<NUM>, and step S2-<NUM>. First, in step S2-<NUM>, the syringe needle <NUM> connected to the first syringe <NUM> filled with the pain relief drug is separated (see the left side), followed by removal of the stopper <NUM> from the prefilled syringe <NUM> prefilled with the temperature-responsive viscous solution (the product DDK gel (Korea Food and Drug Administration Approval No. <NUM>-<NUM>) marketed by the applicant of the present invention) and equipped with a piston (see the right side).

In step S2-<NUM>, the syringe connector <NUM> is connected to the prefilled syringe <NUM> from which the stopper <NUM> was removed, and the first syringe <NUM> filled with the pain relief drug is connected to the prefilled syringe. At this time, care must be taken not to allow the pain relief drug to flow down.

In step S2-<NUM>, the pain relief drug is uniformly mixed with the temperature-responsive viscous solution in the prefilled syringe <NUM> while the pistons of the first syringe <NUM> and the prefilled syringe <NUM> connected to each other by the syringe connector <NUM> are pushed from side to side.

Next, in step S3, the syringe connector <NUM> is separated, and then the mixture solution injection guide tube <NUM> or the second syringe needle <NUM> is connected to the prefilled syringe <NUM>, and the pain relief drug-containing mixture solution is sufficiently injected into a surgical incision site and applied.

If necessary, the method may include, before step S1, a step of sucking and removing the washing solution used in surgery by a suction means (not shown) and confirming that sufficient hemostasis of the wound surface was made during the surgery.

In the following, only examples in which compositions obtained by mixing components as defined in claim <NUM> are according to the claims.

<FIG> show the results of a stability test for the temperature-responsive viscous solution and a release test for the pain relief drug of the mixture of the temperature-responsive viscous solution and the pain relief drug.

The test results are summarized as follows. As shown in <FIG> showing the results of an in vitro stability test for the temperature-responsive viscous solution, it was confirmed that when the temperature-responsive viscous solution was used, the stability thereof was maintained up to <NUM> days, unlike a temperature-responsive polymer. As shown in <FIG> showing the results of a release test for the pain relief drug-containing mixture, it was confirmed that the pain relief drug was released slowly up to <NUM> days (<NUM> hours).

<FIG> shows the pain-reducing/pain-relieving effects on rat paw pain-induced models, obtained when the pain relief drug and the temperature-responsive viscous solution were not used, when the pain relief drug was used alone, when the temperature-responsive viscous solution was used alone, and when the pain relief drug-containing mixture solution was used.

In the figure, the non-use of the pain relief drug and the temperature-responsive viscous solution is marked as control; the use of the temperature-responsive viscous solution alone is marked as DDK; the use of the pain relief drug alone is marked as Ropi. (which is the abbreviation of the substance used) with concentration % (wt% concentration in aqueous solution); and the use of the pain relief drug-containing mixture solution is marked as DDK/Ropi. with concentration %.

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

For reference, Ropi. <NUM>% means a composition containing the temperature-responsive viscous solution (viscous aqueous solution) and the pain relief drug (ropivacaine hydrochloride injection; aqueous drug solution), mixed with each other at a volume ratio of <NUM>:<NUM>, and means that the final drug concentration is <NUM> wt%.

Summarizing the test results, it was confirmed that the pain of the test group treated with the pain relief drug-containing mixture solution was effectively reduced compared to that of the test group treated with the pain relief drug alone.

Therefore, according to the above-described evaluation results, it can be seen that the pain relief drug-containing mixture solution injected by the surgical kit of the present invention is very effective in providing stable and slow release of the drug in the surgical incision site. In particular, it can be confirmed that the pain relief drug-containing drug mixture solution can be stably prepared by a simple procedure whenever needed, and thus the surgical kit is preferable from an economic point of view.

<FIG> shows the results of a stability test performed depending on whether the temperature-responsive viscous solution (containing <NUM> wt% of a temperature-responsive polymer) contained in the pain relief drug- or treatment drug-containing mixture solution was crosslinked. From the test results, it was confirmed that when the content of the temperature-responsive polymer was <NUM> wt% or less (not shown), the stability of the crosslinked temperature-responsive viscous solution was considerably higher than that of the non-crosslinked temperature-responsive viscous solution, but when the content of the temperature-responsive polymer was <NUM> wt% or more (see <FIG>), the stabilities of the crosslinked temperature-responsive viscous solution and the non-crosslinked temperature-responsive viscous solution were all maintained up to <NUM> days, and thus did not substantially differ from each other.

<FIG> shows the results for a precipitation test for a pain relief drug-containing mixture solution (left) and a treatment drug-containing mixture solution (right), which contain a crosslinked temperature-responsive viscous solution. In <FIG>, DDK Gel means a gel composed of poloxamer and crosslinked alginate. From the test results, it was confirmed that in the case of the pain relief drug-containing mixture solution, ibupropene used as the pain relief drug formed a precipitate by reaction with the crosslinking agent CaCl<NUM>, and in the case of the treatment drug-containing mixture solution, the pH of the solution was lowered by gentamicin used as the treatment drug, and thus sodium alginate was precipitated. Namely, when the pain relief drug- or treatment drug-containing mixture solution did not contain the crosslinking CaCl<NUM> or alginate, no precipitate occurred.

<FIG> shows the results of a slow-release test for the pain relief drug (ibuprofen) of the pain relief drug-containing mixture solution. In the slow-release test, an aqueous ibuprofen solution was mixed with a <NUM> wt% solution of poloxamer, containing no crosslinked alginate, at a volume ratio of <NUM>:<NUM>. From the test results, it was confirmed that, in the case of the pain relief drug-containing mixture solution, the drug was released slowly up to <NUM> days (<NUM> hours).

<FIG> show the results of a slow-release test performed while changing the kinds of drug (ropivacaine vs. bupivacaine) and viscous solution (crosslinked vs. non-crosslinked) in the pain relief drug-containing mixture solution. the slow-release test, a <NUM> wt% aqueous solution of the drug was mixed with the temperature-responsive viscous solution (crosslinked alginate, <NUM> wt% poloxamer-containing DDK gel vs. <NUM> wt% poloxamer solution) at a volume ratio of <NUM>:<NUM>. From the test results, it was confirmed that the pain relief drug-containing mixture solution was not significantly influenced by the kind of drug or whether or not the temperature-responsive viscous solution was crosslinked, and all the drugs were released slowly up to <NUM> days (<NUM> hours).

In the present disclosure, the term "crosslinked" means that a crosslinking agent or crosslinked alginate is contained, and the term "non-crosslinked" means that a crosslinking agent or crosslinked alginate is not contained.

Claim 1:
A surgical kit for use in treating or relieving pain at an exposed incision site, comprising:
a prefilled syringe <NUM> filled with a temperature-responsive viscous solution acting as a stabilization matrix for a pain relief or treatment drug, the prefilled syringe having a structure which is opened and closed by a stopper; and a mixture solution injection guide tube <NUM> configured to inject a mixture solution containing the pain relief or treatment drug and the temperature-responsive viscous solution in close proximity to the exposed incision site,
wherein the temperature-responsive viscous solution comprises <NUM> to <NUM> wt% of a poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer containing a poly(ethylene oxide) block and the poly(propylene oxide) block at a ratio of <NUM>:<NUM> to <NUM>:<NUM>, and the balance of water for injection, and has a viscosity of <NUM> to <NUM>,<NUM> cps at <NUM>, a viscosity of <NUM>,<NUM>,<NUM> to <NUM>,<NUM>,<NUM> cps (<NUM> cps corresponds to <NUM> mPA·s) at <NUM>, and a stickiness of <NUM> N or higher measured using a rotational rheometer at <NUM>, wherein the pain relief or treatment drug is used as an aqueous drug solution, and
wherein:
when the pH of the aqueous drug solution is <NUM>-<NUM>, the volume ratio between aqueous drug solution and temperature-sensitive viscous solution is <NUM>:<NUM> to <NUM> (aqueous drug solution: temperature-responsive viscous solution), and
when the pH of the aqueous drug solution is <NUM> to less than <NUM>, the volume ratio between the aqueous drug solution and temperature sensitive viscous solution is <NUM>:<NUM> to <NUM> (aqueous drug solution: temperature-responsive viscous solution), and
wherein the temperature-responsive viscous solution contains an ionically crosslinked alginate in an amount of <NUM> to <NUM> wt% of the temperature-responsive viscous solution, and
wherein the drug is a pain relief drug selected from a local anesthetic, an opiate analgesic, a nonsteroidal drug, and
wherein the aqueous drug solution and the temperature-responsive viscous solution are combined to give a final drug mixture with a concentration in the range of <NUM> to <NUM> wt%; and wherein viscosity is measured with a Brookfield viscometer under conditions of #<NUM> spindle at <NUM> and #<NUM> spindle at <NUM> in accordance with method <NUM> (rotational viscometer method) described in the Korean Pharmacopoeia.