KR20130130403A - Composition for treating or reducing poastoperative wound pain in laparoscopic assisted vaginal hysterectomy - Google Patents

Abstract

The present invention relates to a transdermal composition for treating or alleviating pain after laparoscopic hysterectomy, wherein the composition includes lidocaine as an active ingredient. The present invention can effectively reduce the pain of a patient who had laparoscopic hysterectomy through a simple way of applying the composition according to the present invention to a region where a needle is removed after laparoscopic hysterectomy.

Description

Composition for Treating or Reducing Poastoperative Wound Pain in Laparoscopic Assisted Vaginal Hysterectomy}

The present invention relates to a transdermal administration composition for pain treatment or alleviation after laparoscopic hysterectomy comprising lidocaine as an active ingredient.

More than 20,000,000 patients go through surgical procedures every year. Postoperative pain (pain after incision) or pain that occurs after surgery or trauma injury is a serious and often refractory medical problem.

Pain is usually localized near the surgical site. Postoperative pain may have two clinically important aspects: resting pain, or mechanical pain that develops when the patient is stationary and worsens when moving (cough / sneeze, when in bed, physical therapy, etc.). Can be. The main problem of postoperative pain management for major surgery is that commonly used drugs have many prominent side effects that delay recovery, prolong hospitalization, and put certain vulnerable patient groups at risk for serious complications.

In the management of pain and discomfort, local anesthetics are widely used. Local anesthetics reversibly block excitatory conduction along nerves and other excitatory membranes that primarily utilize sodium channels. Clinically, this action blocks the pain in certain parts of the body. Local anesthetics are generally weak bases. There are three main classes of local anesthetics: ester derivatives (e.g. cocaine, procaine, etc.), amide derivatives (e.g. lidocaine, bupivacaine, etc.), and others (e.g., diclonine, pramoxin ( pramoxine).

Among local anesthetics, lidocaine, 2- (dimethylamino) -N- (2,6-dimethylphenyl) -acetamide, is an intravenous solution that is particularly well known for the treatment of ventricular tachycardia (arrhythmia of the heart) (as an example). US Pat. No. 3,968,205). Lidocaine is also widely used as a vasoconstrictor to reduce topical blood flow by topical application or aerosol (eg, nasal aerosol to reduce nasal congestion) (see US Pat. No. 5,534,242). Lidocaine is also known for its therapeutic effects in reducing postherpetic neuralgia (PHN), nerve damage pain caused by herpes zoster (shingles and postherpetic neuralgia), and similar neuropathy. For example, US Patent RE37,727 discloses a method of administering lidocaine into the dermis by delivering lidocaine from the skin surface to the skin using patches and dressings.

There are two types of hysterectomy: abdominal hysterectomy and vaginal hysterectomy, and recently, Laparoscopic Assisted Vaginal Hysterectomy (LAVH) is mainly used. . Laparoscopic hysterectomy, which is an endoscopic operation, involves a small hole in the abdomen without the need to open the abdomen, and the surgery is performed in the abdominal cavity using the laparoscope, and then the uterus is removed through the vagina, which is more accurate than abdominal hysterectomy. Less scars, less post-operative pain, and less bleeding during the surgery has the advantage of a faster recovery after surgery.

However, patients who complain of severe pain even after laparoscopy due to the injection of intraperitoneal carbon dioxide and trocar insertion into the abdominal wall are increasing. Therefore, it is urgent to develop a method that can effectively reduce the pain of patients undergoing laparoscopic hysterectomy. Therefore, the inventors of the present invention intend to use lidocaine for pain treatment or alleviation of pain after laparoscopic hysterectomy, and after confirming that the lidocaine is excellent in alleviating the postoperative pain in patients undergoing laparoscopic hysterectomy, the present invention To complete.

Accordingly, the present invention aims to provide a novel use of lidocaine, for the treatment or relief of pain after laparoscopic hysterectomy.

In order to solve the above problems, the present invention provides a transdermal administration composition for pain treatment or alleviation after laparoscopic hysterectomy comprising lidocaine (lidocaine) as an active ingredient.

Through a simple method of applying the percutaneous administration composition according to the present invention to the trocar removal site after laparoscopic hysterectomy, the pain of the patient who has undergone laparoscopic hysterectomy can be effectively reduced.

1 is a test result of measuring the pain score (Visual analogue scale (VAS) every 1 hour, 6 hours, 12 hours, 24 hours, 36 hours after surgery in the lidocaine application group and the control group.

The present invention provides a transdermal administration composition for pain treatment or alleviation after laparoscopic hysterectomy comprising lidocaine as an active ingredient.

The lidocaine has an excellent effect of relieving postoperative pain in a patient who has undergone laparoscopic hysterectomy, and thus may be useful for treating or alleviating pain after laparoscopic hysterectomy.

Therefore, the present invention provides a step of administering a transdermal administration composition for pain treatment or alleviation after laparoscopic hysterectomy, which is included as an active ingredient, the use of lidocaine for the preparation of a pain cure after laparoscopic hysterectomy, and a therapeutically effective amount of lidocaine to the subject. It provides a method for treating or alleviating pain after laparoscopic hysterectomy.

In one embodiment of the present invention, the transdermal dosage composition may include 0.01 to 90 parts by weight, 0.1 to 90 parts by weight, 1 to 90 parts by weight, or 10 to 90 parts by weight with respect to 100 parts by weight of transdermal administration composition. However, the present invention is not limited thereto and may vary depending on the condition of the patient and the type and progress of the disease.

In another embodiment of the invention, the transdermal administration composition is a carrier, excipient, disintegrant, sweetener, coating agent, swelling agent, lubricant, lubricant, flavoring agent, antioxidant, buffer, bacteriostatic agent, diluent, dispersant, surfactant, binder And one or more adjuvants selected from the group consisting of lubricants.

Specific examples of carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration may be in the form of tablets, pills, powders, granules, capsules These solid preparations can be prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., into the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin which are commonly used simple diluents. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

In another embodiment of the present invention, the transdermal administration composition may be formulated for topical skin application, and more specifically, may be formulated in a polymer matrix, cream, gel, emulsion or ointment, but is not limited thereto.

In one embodiment of the present invention, the transdermal administration composition may further include other pharmaceutical active ingredients having different pharmacokinetics and pharmacodynamics in addition to lidocaine. More specifically, any one or more substances selected from the group consisting of tetracaine, bupivacaine, prilocaine, mepivacaine, procaine, chloroprocaine, lopivacaine, dibucaine, ethidocaine and benzocaine are added. It may include, but is not limited to.

In another embodiment of the present invention, the transdermal administration composition may be applied through a method applied to the outer surface of the surgically closed wound 1-3 times a day after laparoscopic hysterectomy.

As used herein, the term “surgically closed wound” refers to any wound that is closed such that the opposing edges of the skin—including wounds—are joined together by a device or material. Surgically closed wounds include, but are not limited to, wounds closed by sutures (absorbent or nonabsorbent, synthetic or natural), staples, and biological glue. More specifically, the trocar removal site generated during laparoscopic hysterectomy may correspond to this, but is not limited thereto.

In one embodiment of the present invention, the transdermal administration composition may be contained in a patch applied adjacent to the surface of a surgically closed wound. Preferably, the patch component resembles the viscoelastic properties of the skin, to conform to the skin during movement to prevent excessive shearing and delamination.

As used herein, a "patch" comprises a transdermal dosage composition and a cover layer formulated for at least topical skin application, thus placing the patch on a surgically closed wound to bring the patch / drug formulation to the surface of the wound. Can be placed adjacent to. Preferably the patch is designed to maximize drug delivery into the dermis through the stratum corneum, upper epidermis, minimize absorption into the circulation, reduce lag time, promote uniform absorption, and reduce mechanical frictional release. .

The preferred dosage of the transdermal administration composition may vary depending on the condition and weight of the patient, the type and extent of the disease, the form of the drug, the route of administration and the duration and may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, the daily dose may be 0.01 to 1,000 mg / kg, specifically 0.1 to 1,000 mg / kg, more specifically 0.1 to 100 mg / kg, though it is not limited thereto. In one embodiment of the invention, the transdermal administration composition may be applied to the outer surface of the surgically closed wound 1 to 3 times, preferably twice a day, when used in the form of the patch is a patch But may be replaced every 16 hours, but is not limited thereto.

In the present invention, the 'subject' may be a mammal including a human, but is not limited thereto.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example  1> Lidocaine Patch  Review of pain control effects of formulations

1. Experimental Method

Forty patients who underwent laparoscopic hysterectomy at Gwandong University Cheil Hospital were analyzed by prospective, double-blind, randomized controlled trial. The indications for surgery included uterine fibroids, adenomyosis, endometriosis, endometrial hyperplasia, abnormal uterine bleeding, and the like.

Factors such as age, weight, disease, type of operation, time of operation, degree of walking and average hospital stay were not significantly different between 20 experimental groups and 20 control groups, which are shown in Table 1.

[Table 1]

LAVH, laparoscopic assisted vaginal hysterectomy

CIS, Carcinoma in situ

LM, laparoscopic myomectomy

One lidocaine patch (700 mg lidocaine, 10 × 14 cm) was applied in quarters (1/4 × 700 = 175 mg, 5 × 7 cm) at each site of trocar removal, and each patch was replaced with a new one every 12 hours. Therefore, if the number of trocar sites is 4, the total daily dose of lidocaine is (175 mg X 4) X2 = 1400 mg / 24 hours; if the number of trocar sites is 3, the total daily dose is (175 mg X 3) X2 = It was set as 1050 mg / 24 hours. The test group was covered with a gauze (10 × 10 cm Medix) on the lidocaine patch to prevent the patch from being seen, and the control group also covered the same gauze on the surgical wound so that the external differences did not differ between the two groups.

The patch information used is as follows.

1) Common name of main ingredient : lidocaine

2) Product Name: Lidotopic (Lidogesic®, icure, Inc., Korea) Specialty Drug, Classification Number: 264

3) Raw material drug and quantity : 5% lidocaine (USP) base 700mg / patch

4) Formulation: One side is cataplasma, which is covered with plastic film with a weak adhesive characteristic of white to light yellow, and one side is made of non-woven fabric.

As supplementary analgesics, 50 μg of fentanyl and Tarasyn (ketorolac tromethamine, 1 ampule: 30 mg) were administered intravenous at the discretion of the physician. If patient pain was not reduced, 25 mg of Demerol (pethidine, 1 ampule: 50 mg) was administered intramuscularly.

After that, the pain score (Visual analogue scale (VAS)) was recorded in a survey form every 1 hour, 6 hours, 12 hours, 24 hours, and 36 hours after surgery. The patient was marked on the 100mm line from no pain to very severe pain.

We also used verbal rating pain scales (VRS) as other pain scores.

(0 if no pain when coughing, 1 when not breathing, 1 when not coughing, no breathing when normal, but 2 pain when breathing, 3 pain when breathing normally, 4 severe pain when breathing)

In addition, the presence of shoulder pain, upper abdominal pain, nausea, vomiting, wound area pain, the most painful part of the trocar area, and the extent of itching in the surgical area were analyzed.

2. Experimental results

The results are shown in Fig.

Referring to FIG. 1, the experimental group to which lidocaine was applied showed a very low VAS score 1 and 6 hours after surgery compared to the control group (P = 0.005 and <0.0005, respectively).

More specifically, the postoperative 1 hour VAS score for postoperative pain at rest was lower than that of the control group in the lidocaine-treated experimental group (P = 0.045). The VAS score for postoperative pain during walking or moving was not significantly different from the control group. The VRS score (5 stages) for postoperative pain was lower than the control group at 6 hours and 12 hours after the operation in the lidocaine-treated experimental group (P = 0.015 and 0.035, respectively). The mean pain score gradually decreased over time.

Shoulder pain, epigastric pain, wound area pain, and pain in the trocar were similar in both experimental and control groups.

In addition, supplementally administered analgesics were also shown in similar amounts in both the experimental and control groups. More specifically, referring to Table 2, the dose of Ketorolac was 7.5 mg [range 0-60 mg] and 20 mg in the experimental and control groups, respectively. range 0-60 mg (P = 0.117), and dermarol doses were similarly similar to 0 mg [range 0-25 mg] and 0 mg [range 0-50 mg] in the experimental and control groups, respectively. (P = 0.077).

[Table 2]

Postoperative nausea and vomiting were also similar in both experimental groups 1, 6, 12, 24 and 36 hours after surgery. Some wounds, contact dermatitis and systemic side effects due to lidocaine patch were reported. No bar was found.

Therefore, through the above experiments, it was confirmed that the early pain after surgery corresponding to 1 to 6 hours after the surgery by the percutaneous application of the lidocaine patch formulation to the patients who underwent laparoscopic hysterectomy.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that such detail is solved by the person skilled in the art without departing from the scope of the invention. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (4)

A transdermal administration composition for pain treatment or alleviation after laparoscopic hysterectomy comprising lidocaine as an active ingredient. The method of claim 1,
The transdermal administration composition is a percutaneous administration composition for pain treatment or alleviation after laparoscopic hysterectomy that is formulated into a polymer matrix, cream, gel, emulsion or ointment. The method of claim 1,
The transdermal administration composition is a percutaneous administration composition for pain treatment or alleviation after laparoscopic hysterectomy that is applied to the outer surface of the surgically closed wound after laparoscopic hysterectomy. The method of claim 1,
Laparoscopic further comprising any one or more compounds selected from the group consisting of tetracaine, bupivacaine, prilocaine, mepivacaine, procaine, chloroprocaine, ropivacaine, dibucaine, ethidocaine and benzocaine Percutaneous administration composition for pain treatment or relief after lower hysterectomy.

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