KR20170025011A - Pharmaceutical composition for sustained release of pain-relieving drugs and a device for administration thereof - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for sustained release of a pain relief medicament and a dosing device for administration thereof, and more particularly to a first composition comprising a fibrinogen coagulation promoting factor; And a second composition comprising a fibrinogen solution, wherein at least one of the first composition and the second composition comprises a pain relief drug carried on a biodegradable polymer, And to an administration device for administration thereof.
The pharmaceutical composition according to the present invention can be used not only for the direct injection of the surgical site before the surgical site, but also for the surgical site during the surgical procedure, . In addition, since the pharmaceutical composition according to the present invention can extensively extend the duration of drug efficacy according to the single injection, it is possible not only to increase patient compliance, but also to ultimately reduce drug costs. Furthermore, since the pharmaceutical composition according to the present invention can introduce various water-soluble or lipid-soluble drug species, it is desirable to develop a sustained-release pharmaceutical preparation for various uses such as anti-inflammatory, anticancer, It is possible.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pharmaceutical composition for sustained release of a pain relieving drug,

The present invention relates to a pharmaceutical composition for sustained release of a pain relief medicament and an administration device for administration thereof.

After surgical operations such as lung cancer surgery, the patient continues to have severe pain in the nervous system at the operation site and chronic pain continues to be maintained over a long period of time even after the pain caused by surgery is alleviated. Therefore, as a treatment for postoperative acute pain, a method of relieving the pain of a patient by attaching a drug storage device through which a painkiller is continuously discharged is attached through a surgical procedure is widely used. However, there is a problem that such a device has an external drug storage device, which limits the activity of the patient, and there is a risk of additional infection. In addition, after the treatment for relieving acute pain is completed, the patient is discharged after removing the drug storage device, but it is reported that the patient feels a great pain even after discharge. Therefore, for patients who complain of long-term pain even after discharge, follow-up measures such as prescribing analgesics are taken, but this causes problems of drug abuse and furthermore, the duration of the pain continues for several months depending on the patient The sensitivity to the drug is lowered, which may cause side effects to the patient's body.

In addition to the drug injection device for acute pain relief, there is also a method of injecting a one-shot pain-suppressing drug to suppress local pain of a patient, which has been widely used for medical use because of its rapidity of drug efficacy. However, the duration of drug efficacy of such a one-shot pain inhibiting drug is only 2 hours to 9 hours, and thus there is a problem that long-term pain suppressing effect can not be expected. Accordingly, there is a demand for development of a new pain medicine that has a long-lasting effect.

With regard to pain relief or anesthetic compositions, Korean Patent Laid-Open Publication No. 2013-0136595 discloses a continuous topical anesthetic composition comprising a sugar ester such as SAIB, which comprises an anesthetic composition containing a non-polymeric carrier material and an anesthetic component , ≪ / RTI > which relates to a composition that allows sustained local anesthesia without excessive drug release initially. Korean Patent Laid-Open Publication No. 1998-0020587 discloses a sustained-release local anesthetic agent and a method for producing the same. The main ingredient is composed of 25 to 75% by weight of a local anesthetic agent and 25 to 75% by weight of a biodegradable polymer, and dexamethasone Or a pharmaceutically acceptable salt thereof.

However, in the case of the previously reported pain relief or anesthetic composition, its duration is not long, and therefore it is not suitable for application to the post-surgical healing process accompanied by extreme long-term pain, There is a problem in that it is not easy to induce a rapid and effective pain relief effect due to the fact that it is not a formulation directly applied to a site.

Patent Document 1: Korean Patent Laid-Open Publication No. 2013-0136595 Patent Document 2: Korean Patent Laid-Open Publication No. 1998-0020587

Accordingly, in order to solve the problems of the prior art, the present invention can overcome the short drug efficacy period of the conventional drug treatment method for delivering a drug for pain relief and enable long-term drug delivery directly to the affected part of the patient , A pharmaceutical composition for sustained release of pain relief medicines.

In order to solve the above problems,

A first composition comprising a fibrinogen coagulation promoting factor; And

A second composition comprising a fibrinogen solution

Wherein at least one of the first composition and the second composition comprises a pain relieving drug carried on a biodegradable polymer. The present invention also provides a pharmaceutical composition for sustained release of a pain relieving drug.

According to one embodiment of the present invention, the biodegradable polymer is selected from the group consisting of poly (lactic-co-glycolic acid) (PLGA), polyvinyl alcohol, polyethylene glycol, poly (caprolactone) (Glycolic acid), poly (hydroxyalkanoate), poly (3-hydroxybutyrate), copolymers thereof, and mixtures thereof.

According to another embodiment of the present invention, the pain relief medicament is selected from the group consisting of bupivacaine, lidocaine, tetracaine, epinephrine, acetylsalicylic acid, paracetamol, morphine, pethidine, naloxone and mixtures thereof Lt; / RTI >

According to another embodiment of the present invention, the fibrinogen coagulation promoting factor may be selected from the group consisting of thrombin, a blood coagulation promoting enzyme and a mixture thereof.

According to another embodiment of the present invention, the first composition or the second composition may further comprise the pain relief medication.

According to another embodiment of the present invention, the pain relief medicament may be carried in an amount of 1 to 40 parts by weight based on 100 parts by weight of the biodegradable polymer.

According to another embodiment of the present invention, the second composition may be contained in an amount of 70 to 130 parts by weight based on 100 parts by weight of the first composition.

According to another embodiment of the present invention, the pain relieving drug may be contained in an amount of 5 to 50 parts by weight based on 100 parts by weight of the first composition or the second composition.

According to another embodiment of the present invention, the pharmaceutical composition is separately accommodated in the first composition and the second composition before being applied to the pain area of the patient, and simultaneously applied to the pain area of the patient at the time of application And mixed.

The present invention also provides an administration device for administering the pharmaceutical composition according to the present invention,

A first receiving portion for receiving the first composition;

A second receiving portion for receiving the second composition;

A pressing means provided at one end of each of the first accommodating portion and the second accommodating portion for simultaneously extruding the first composition and the second composition from the first accommodating portion and the second accommodating portion, respectively;

A mixing tube for mixing the first composition and the second composition coextruded from the first accommodating portion and the second accommodating portion; And

And an administration part for administering the mixed composition transferred from the mixing tube to the pain site of the patient.

The pharmaceutical composition according to the present invention can be used not only for the direct injection of the surgical site before the surgical site, but also for the surgical site during the surgical procedure, . In addition, since the pharmaceutical composition according to the present invention can extensively extend the duration of drug efficacy according to the single injection, it is possible not only to increase patient compliance, but also to ultimately reduce drug costs. Furthermore, since the pharmaceutical composition according to the present invention can introduce various water-soluble or lipid-soluble drug species, it is desirable to develop a sustained-release pharmaceutical preparation for various uses such as anti-inflammatory, anticancer, It is possible.

FIG. 1A is a schematic view illustrating a process in which a pain relieving drug loaded on a biodegradable polymer is released from a biodegradable polymer-pain relief drug complex as a biodegradable polymer is decomposed over time, FIG. 1B is a view Lt; RTI ID = 0.0 > drug release < / RTI > by secondary drug release from the fibrin clot.
Figure 2 is a schematic view of a dosing device according to the invention.
FIGS. 3A to 3C are graphs showing SEM photographs (3a and 3b) of microparticles composed of a biodegradable polymer carrying a bulky buccane in the preparation of the composition according to the present invention, and microparticles composed of a biodegradable polymer carrying lidocaine SEM picture (3c).
4A and 4B are graphs showing the drug release characteristics (4a) of the microparticles of the biodegradable polymer carrying the volatile saccharide (4a) and the drug release characteristics of the microparticles of the biodegradable polymer carrying the lidocaine (4b).
5a and 5b are graphs showing the drug release characteristics (5a) of a pharmaceutical composition comprising microcapsules of microbubbles loaded with a volumetric bacillus and the biodegradable polymer carrying lidocaine (5b) of a pharmaceutical composition comprising microparticles.

Hereinafter, the present invention will be described in more detail with reference to the drawings and examples.

The present invention relates to a biodegradable polymer, a pain relieving drug, a fibrinogen, and a fibrinogen, in order to release a pain relieving drug stably in a patient's pain area by supporting a pain relieving drug in a biodegradable polymer, Utilize the interaction between the coagulation promoting factors.

Therefore, in the present invention,

A first composition comprising a fibrinogen coagulation promoting factor; And

A second composition comprising a fibrinogen solution

Wherein at least one of the first composition and the second composition comprises a pain relieving drug carried on a biodegradable polymer. The present invention also provides a pharmaceutical composition for sustained release of a pain relieving drug.

The pharmaceutical composition according to the present invention is separately contained in the first composition and the second composition before being applied to the pain area of the patient, and is mixed and mixed with the pain area of the patient at the time of application. This is because, when the fibrinogen coagulation promoting factor contained in the first composition and the fibrinogen solution contained in the second composition are mixed with each other, the fibrin protein forms and coagulates, so that the coagulation of the composition according to the present invention is applied to the pain area of the patient This is because it should not be started before. Therefore, the fibrinogen coagulation promoting factor in the first composition, which is separately contained in a separate receptor before being applied to the pain area of the patient, and the fibrinogen in the second composition are mixed with each other after the application to the pain area of the patient, Lt; / RTI > Meanwhile, examples of the fibrinogen coagulation promoting factor include thrombin, various hemocoagulase, or a mixture thereof.

In the pharmaceutical composition of the present invention, the biodegradable polymer may be a poly (lactic-co-glycolic acid) (PLGA), polyvinyl alcohol, polyethylene glycol, (Hydroxy acid), poly (hydroxyalkanoate), poly (3-hydroxybutyrate), copolymers thereof, and mixtures thereof, and the pain relieving drugs carried thereon may be selected from the group consisting of bupivacaine, lidocaine, tetra May be selected from the group consisting of catechol, epinephrine, acetylsalicylic acid, paracetamol, morphine, pethidine, naloxone, and mixtures thereof. Particularly, when PLGA is used as a biodegradable polymer, since PLGA is a polymer in which a hydrophilic component and a hydrophobic component are present together, it is possible to effectively support a pain relief drug regardless of whether the drug to be supported is hydrophilic or hydrophobic .

In the present invention, since the pain relief drug is primarily supported on the biodegradable polymer as described above, the primary drug release effect can be obtained. Figure 1a is over a pain relief drug supported on the biodegradable polymer of time the biodegradable polymer is a biodegradable polymer according to the decomposed - When was schematically showing a process of exiting the pain relief drug complex, with reference to Figure 1a, T ₀ As the time elapses from the time point to the time point T ₃ , the biodegradable polymer is decomposed to decrease the diameter, thereby slowly releasing the pain-relieving drug trapped in the biodegradable polymer-drug complex. Furthermore, as shown in Fig. 1b, in the complex according to the present invention, the pain relieving drug is primarily released from the micro-sized particles, and after the primary drug release is thus made, the fibrin clot Thereby acting as a shielding film for preventing rapid drug release, and as a result, a further improved drug release delay effect can be achieved.

The biodegradable polymer-pain relief drug complex is prepared by dissolving the biodegradable polymer and the pain relief drug simultaneously in an organic solvent such as methylene chloride, mixing and stirring the aqueous solution with a predetermined amount of the surfactant dissolved therein, Evaporation of the solvent components and separation of the resulting micro-sized complexes by centrifugation. At this time, the content of the pain relieving drug carried on the biodegradable polymer not only affects the pain relieving degree of the patient but also affects the sustained release of the drug. In the present invention, the pain relieving drug is the biodegradable polymer Preferably 1 to 40 parts by weight, based on 100 parts by weight of the composition. When the content of the pain relieving drug is less than 1 part by weight, sufficient pain relief can not be attained. When the content of the pain relieving drug is more than 40 parts by weight, sufficient side effect can not be obtained.

Such pain-relieving drugs may be further contained in addition to the pain-relieving drugs carried on the biodegradable polymer, depending on the use of the pharmaceutical composition according to the present invention. That is, the pain relief drug carried on the biodegradable polymer exists in the form of a biodegradable polymer-pain relief drug complex, and is gradually released along with the degradation of the biodegradable polymer. However, in the case of the additional pain relief drug, The pain of the pain can quickly alleviate. Thus, depending on the degree of pain and the treatment plan for the patient, an additional pain relief medication may be further included. In this case, the content of the additional pain relief medicament may be 5 to 50 parts by weight based on 100 parts by weight of the first composition or the second composition.

Furthermore, the secondary drug release effect of the pharmaceutical composition according to the present invention can be improved by the combination of the fibrinogen coagulation promoting factor contained in the first composition and the fibrinogen solution contained in the second composition, have. That is, the first composition and the second composition are mixed when administered to a wound area of a patient, whereby the fibrinogen coagulation promoting factor and the fibrinogen solution react with each other to form fibrin fibrin, and the fibrin formed is a pain- The effect of delaying the release of the drug is further exerted. Therefore, the pharmaceutical composition according to the present invention can provide a secondary drug release effect by fibrin, in addition to a primary drug release effect by the biodegradable polymer-pain relief drug complex, Lt; / RTI >

On the other hand, the relative content of the first composition and the second composition also affects the properties such as the drug release profile, and preferably the second composition comprises 70 parts by weight to 130 parts by weight When the content of the second composition is less than 70 parts by weight, the fibrin clot quickly coagulates due to the action of a relatively large amount of thrombin. This is because the mixture is introduced into the affected part at the connection part of the injector injection part There is a problem that the syringe injection part may be clogged because it causes agglutination before, and when the amount is more than 130 parts by weight, the content of thrombin to the fibrinogen in the mixing process is so small that the coagulation time delay and the effect of releasing the drug due to incomplete fibrin aggregation formation And the like.

In addition, the pharmaceutical composition according to the present invention can be administered in an appropriate amount depending on the body weight, age, pain level, etc. of the patient. For example, the pain relief medication contained in the pharmaceutical composition For example, a dose of 2 mg / kg or less may be applied based on the volume of the solution.

As described above, the pharmaceutical composition according to the present invention requires that the first composition and the second composition are separated and accommodated before being applied to the pain area of the patient, Bars, specially designed dosing devices are used for this purpose. Therefore, an apparatus for administering a pharmaceutical composition according to the present invention,

A first receiving portion for receiving the first composition;

A second receiving portion for receiving the second composition;

A pressing means provided at one end of each of the first accommodating portion and the second accommodating portion for simultaneously extruding the first composition and the second composition from the first accommodating portion and the second accommodating portion, respectively;

A mixing tube for mixing the first composition and the second composition coextruded from the first accommodating portion and the second accommodating portion; And

And an administration part for administering the mixed composition transferred from the mixing tube to the pain site of the patient.

2 shows a schematic view of a dosing device according to the present invention. Referring to FIG. 2, the dosing device according to the present invention comprises a first receiving part 210 for receiving a first composition and a second receiving part 210 for receiving a second composition 2 accommodating portion 220. The one end of each of the first and second accommodating portions 210 and 220 is provided with a pressing means 230 for pressing and extruding the compositions contained in the respective accommodating portions. The first and second compositions contained in the first and second accommodating portions 210 and 220 are extruded in the direction of the outlet of the accommodation portion when the pressing means 230 is pressed when the applicator is applied to the wound area of the patient, 1 and a mixing tube 240 for mixing the second composition are connected. Next, the composition mixed in the mixing tube 240 is administered to the injured area of the patient through the injection unit 250 such as an injection needle, and after the administration, the fibrinogen coagulation promoting factor in the first composition and the The fibrinogen solution reacts to form fibrin.

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are intended to assist the understanding of the present invention and should not be construed as limiting the scope of the present invention.

Example

Preparation of Biodegradable Polymer-Pain Relief Drug Complex

500 mg of poly (lactic-co-glycolic acid) (PLGA), a biocompatible polymer, and 300 mg of bupivacaine, a pain relieving drug supported on the biocompatible polymer, were simultaneously dissolved in 12 g of methylene chloride (MC) The dissolved solution was mixed with 100 g of deionized water in which 1 g of polyvinyl alcohol (PVA) had been dissolved and stirred at 400 rpm for 1 hour. At this time, the MC used for PLGA dissolution was evaporated using a vacuum pump at the same time as stirring. After the stirring was completed, the resulting microparticles were separated using a filter having a constant pore size of 250 mu m and then centrifuged. The obtained microparticles were washed with deionized water four to five times to remove PVA, and the process of obtaining again using a centrifuge was repeated. Finally, residual water was completely removed using a freeze dryer to obtain 570 mg of a dry powder.

On the other hand, 8 kinds of microparticles having different contents of volumetric baccain per 1 mg of microparticles were prepared as shown in Table 1 by varying the amounts of PLGA and bupivicaine and changing the process conditions.

turn PLGA composition
(PLA: PGA) Bupivacaine / PLGA (mg / mg) Bupivacaine content
(占 퐂 / 1 mg microparticles) One 50:50 10/500 12.4 2 50:50 20/500 36.3 3 50:50 50/500 110.9 4 50:50 100/500 183.6 5 50:50 200/500 270.1 6 50:50 300/500 351.2 7 50:50 400/500 -

In the above Table 1, the content of bupivacaine was determined by dissolving 10 mg of the drug-bearing microparticles prepared in 1 ml of DMF and measuring the absorbance at an absorption region of 272 nm by using a UV-Vis spectroscopy, Respectively.

As shown in Table 1, it can be seen that the microparticles of the No. 5 condition exhibit the best content of the volatile components. If the amount of the drug introduced is excessive, it is impossible to dissolve the drug in the microcapsules. FIGS. 3A and 3B show SEM photographs of microparticles No. 5 in Table 1 above.

On the other hand, lidocain-bearing microparticles were also prepared in the same manner as described above, except that lidocaine was used as a pain relief drug, and FIG. 3c shows SEM photographs of lidocain-bearing microparticles.

As can be seen in Table 1, various microparticles having different amounts of drug for end-product were prepared with different amounts of the pain-relieving drug relative to the weight of the biodegradable polymer. Also, it can be selectively used according to the target amount of transmission.

Drug release characteristics with in-bit of microparticles over time

Of the microparticles prepared above, the drug release characteristics of the 5th microparticles of Table 1 over time were analyzed by HPLC (High-performance liquid chromatography). 20 mg of the above-prepared volumetric buffered microparticles was mixed with 5 ml of PBS (pH 7.4) buffer, 1 ml of the solution was taken at fixed times, and 1 ml of fresh PBS buffer solution was filled again. The amount of drug released in 1 ml of PBS obtained at the above time was acquired and calculated using an HPLC (mobile phase, ACN: pH 2.5 buffer = 15: 85) at an injection volume of 20 μl, 4A. Similarly, drug release characteristics for the microparticles containing the lidocaine prepared above were also analyzed, and the results are shown in FIG. 4B. Referring to FIGS. 4A and 4B, it can be seen that the microparticles gradually release bupivacaine and lidocaine over a long period of up to about 20 days.

Injectable  Preparation and release of the drug according to the invention in vitro with time

A first composition solution was prepared by uniformly mixing 20 mg of the microparticles under Condition 5 in Table 1 and 2.28 mg of thrombin in 0.3 ml of Na-citrate and NaCl solution. In addition, a second composition solution was prepared by uniformly mixing 27 mg of fibrinogen in human Factor XIII, human albumin, arginine HCl, isoleucine, Na-citrate, and 0.3 ml of NaCl solution. The first composition and the second composition were injected into different syringes and then mounted on a two-syringe clip as shown in FIG. The first and second compositions were mixed in the end mixing tube by simultaneously pressing the respective injectors with pressure, and the mixture was applied to the affected part simultaneously with the mixing. It was confirmed that a fibrin clot was formed within a few seconds of the application of the affected part.

The drug release characteristics of the injectable form over time were obtained according to the schedule set forth in the drug release experiment with the beads in the pH 7.4 PBS buffer solution, and analyzed using HPLC. The results are shown in FIG. 5A. Specifically, the fibrin clusters formed with the drug-loaded microparticles were immersed in 5 ml of PBS 7.4 PBS buffer, placed in a 37 ° C. incubator, and then 1 ml Of pH 7.4 PBS buffer was taken and filled with fresh 1 ml of pH 7.4 PBS buffer. The samples obtained by the date were quantitatively analyzed using HPLC. Referring to FIG. 5A, the drug release capacity of the composition according to the present invention is extended to about 35 days.

The drug release characteristics were also analyzed for a composition containing microcapsules containing lidocaine by the same method, and the results are shown in FIG. 5B. Similarly in FIG. 5b, it can be seen that the drug-releasing ability lasts for more than 30 days.

As shown in Table 2 below, various compositions were prepared by varying the content ratios of the first composition and the second composition. :

turn The first composition (thrombin solution) mg The second composition (fibrinogen solution) mg Microparticle loading mg mg The ratio of the second composition to the first composition (%) Fibrin aggregate
Evaluation of solidification One 200 120 20 60 Injector internal solidification 2 200 140 20 70 normal 3 200 160 20 80 normal 4 200 180 20 90 normal 5 200 200 20 100 normal 6 200 220 20 110 normal 7 200 240 20 120 normal 8 200 260 20 130 normal 9 200 280 20 140 Coagulation delay

Referring to Table 2, in the case of samples No. 2 to No. 8 in which the content of the second composition was in the range of 70 to 130 parts by weight based on 100 parts by weight of the first composition, normal fibrin aggregates were formed, In the case of sample No. 1, the fibrin clot becomes too fast due to excessive thrombin content, resulting in the clotting of the inside of the injector. Conversely, in the case of sample No. 9 exceeding the above range, the thrombin content is too small, Is delayed.

Pain relief medication Additionally  Manufacture of the included composition

As a composition for acute pain relief, a composition comprising an additional volumetric baccain in a second composition comprising a fibrinogen solution was prepared. At this time, the second composition and the first composition were fixed at a ratio of 1: 1. In the case of the microparticles carrying the pain relieving drug, the content of the pain relieving drug in the particles was 270 μg per 1 mg of microparticles, Was adjusted to 40 mg, and the drug release characteristics were evaluated while changing the content of the additional volatile baker in the second composition. At this time, if the content of the additional volumetric volumetric content was excessive, the formation of the fibrin aggregate was inhibited. Referring to Table 3 below, the content of the additional volumetric volumetric content was more than 50 parts by weight based on 100 parts by weight of the second composition. No fibrin clot was formed in the sample.

turn Microparticle weight (mg) Additional incorporated volumetric weight (mg) Weight of first composition (mg) Weight of the second composition (mg) Fibrin formation solid formation day 7 Evaluation of drug release One 40 10 200 200 possible 72.18% 2 40 20 200 200 possible 76.32% 3 40 50 200 200 possible 81.36% 4 40 100 200 200 possible 83.64% 5 40 150 200 200 Non-clotting   -

Claims (10)

A first composition comprising a fibrinogen coagulation promoting factor; And
A second composition comprising a fibrinogen solution
Wherein at least one of the first composition and the second composition comprises a pain relief drug carried on a biodegradable polymer. ≪ RTI ID = 0.0 > 8. < / RTI > The biodegradable polymer of claim 1, wherein the biodegradable polymer is selected from the group consisting of poly (lactic-co-glycolic acid) (PLGA), polyvinyl alcohol, polyethylene glycol, poly (caprolactone), poly (lactic acid) ), Poly (hydroxyalkanoate), poly (3-hydroxybutyrate), copolymers thereof, and mixtures thereof. The pharmaceutical composition for sustained release of pain relief medicament. The composition of claim 1, wherein the pain relieving drug is selected from the group consisting of bupivacaine, lidocaine, tetracaine, epinephrine, acetylsalicylic acid, paracetamol, morphine, pethidine, naloxone, ≪ / RTI > The pharmaceutical composition for sustained release of a pain relieving drug. 2. The pharmaceutical composition according to claim 1, wherein the fibrinogen coagulation promoting factor is selected from the group consisting of thrombin, blood coagulation promoting enzyme and mixtures thereof. The pharmaceutical composition of claim 1, wherein said first composition or said second composition further comprises said pain relief medication. The pharmaceutical composition for sustained release of pain-relieving drugs according to claim 1, wherein the pain-relieving drug is contained in an amount of 1 to 40 parts by weight based on 100 parts by weight of the biodegradable polymer. The pharmaceutical composition for sustained release of pain relief medicament according to claim 1, wherein the second composition is contained in an amount of 70 to 130 parts by weight based on 100 parts by weight of the first composition. 6. The pain relief medication according to claim 5, wherein the pain relief medication is contained in an amount of 5 to 50 parts by weight based on 100 parts by weight of the first composition or the second composition. Composition. The method of claim 1, wherein the pharmaceutical composition is separately applied to the pain area of the patient, and the first composition and the second composition are separated and accommodated, A pharmaceutical composition for sustained release of a pain relief medication. A first receiving portion for receiving the first composition;
A second receiving portion for receiving the second composition;
A pressing means provided at one end of each of the first accommodating portion and the second accommodating portion for simultaneously extruding the first composition and the second composition from the first accommodating portion and the second accommodating portion, respectively;
A mixing tube for mixing the first composition and the second composition coextruded from the first accommodating portion and the second accommodating portion; And
10. An apparatus for administering a pharmaceutical composition according to any one of claims 1 to 9, comprising an administration section for administering the mixed composition delivered from the mixing tube to the pain site of the patient.

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