KR20120128393A - Aanalgesic composition containing fibrinogen or fibrin as an active ingredient - Google Patents

Abstract

PURPOSE: An analgesic composition containing fibrinogen and a composition for preventing and/or treating joint-related disorders are provided to ensure safety and compatibility. CONSTITUTION: An analgesic composition contains 5-100 mg/ml of fibrinogen, fibrin, or a mixture thereof as an active ingredient. The analgesic composition additionally contains thrombine, calcium, or aprotinin. The analgesic composition is manufactured in a form of direction injection. A pharmaceutical composition for preventing or treating joint or ligament contains the fibrinogen, fibrin, or a mixture thereof as an active ingredient. The pharmaceutical composition additionally contains thrombine, calcium, or aprotinin.

Description

Analgesic composition containing fibrinogen or fibrin as an active ingredient {Aanalgesic composition containing fibrinogen or fibrin as an active ingredient}

An analgesic composition comprising fibrinogen and / or fibrin as an active ingredient and a composition for preventing and / or treating a joint or ligament-related disease.

Fibrinogen is a precoagulant that normally exists in the blood. When collagen and the like are exposed to blood vessels due to damage to blood vessels, platelets aggregate and various chemicals are linked therefrom. Finally, thrombin and calcium act on fibrinogen to form fibrin to form a coagulant on the exposed collagen. do.

On the other hand, hyaluronic acid (hyalunonic acid) currently used as a pain treatment is a component of cartilage and a component of joint fluid. Hyaluronic acid is used alone for the purpose of treating arthritis or the like or is administered in the joint cavity together with a steroid-based drug, and shows a good effect in the treatment of shoulder or knee pain.

However, hyaluronic acid, which is used as a pain medicament, appears to have a nonuniform effect according to the progress of the disease, and has a disadvantage in that absorption occurs earlier than expected.

Therefore, there is a need for the development of a pain cure agent that can maintain a certain level of pain treatment effect regardless of the extent of disease progression, and the pain treatment effect can be maintained continuously.

One example of the present invention provides an analgesic composition comprising fibrinogen and / or fibrin as an active ingredient.

Another example provides a composition for preventing and / or treating a joint or ligament-related disease comprising fibrinogen and / or fibrin as an active ingredient.

The present inventors completed the present invention by confirming that fibrinogen is excellent in alleviating the pain caused by arthritis and / or shoulder ligament injury and inhibiting the progression of arthritis.

Fibrinogen solution was found to be viscous in itself, similar to hyaluronic acid, to protect cartilage and ligaments.

Coagulation is better at areas where collagen is exposed, and coagulation is better when inflamed. Arthritis is an inflamed area, rich in calcium and exposed to a lot of collagen theoretically fibrin clot (fibrin clot) can be formed better than other sites.

As a result of the formation of a thrombus in the damaged joint, the function of protecting the damaged joint is better and delays the absorption of the steroidal drug administered together, thereby prolonging the drug effect, thereby inhibiting the progression of arthritis and effectively treating pain. ) You can get the effect. Since the pain inhibitory effect of fibrinogen is due to the formation of thrombi, an equivalent effect can be obtained even by administering fibrin, which is an activated form of fibrinogen.

Once the blood clots are formed at the site of injury, they dissolve by inducing a thrombolytic mechanism, but this is a mechanism occurring in the joint cavity outside the human tissue. Therefore, the blood clot has a long dissolution period, which is why the antithrombotic effect of hyaluronic acid is superior to the analgesic effect. do.

Thus, one embodiment of the present invention provides an analgesic composition comprising fibrinogen and / or fibrin as an active ingredient.

Pain that may have analgesic effects by the analgesic composition of the present invention may be pain due to inflammation and / or damage to joints, cartilage, and / or ligaments, and the pain area may be any joint area such as shoulder, knee, It may be any area where joints and ligaments exist, such as elbows, ankles, soles, wrists, fingers, and toes.

In addition, the pain may be pain due to arthritis or ligament inflammation and / or injury disease, for example, knee pain caused by degenerative arthritis, shoulder pain caused by fifty shoulders, arthritis of joints such as wrists, ankles, elbows, fingers, and toes. Pain, ligaments located on the wrist, ankle, sole, elbow, etc. may be a disease that is damaged or inflamed, such as pain caused by desturvin's disease, plantar fasciitis, tennis elbow, golf elbow and the like.

In one embodiment, the analgesic composition according to the present invention is particularly effective in the treatment of pain caused by degenerative arthritis of the knee or damage to the shoulder ligament.

In addition, the inventors have confirmed that the analgesic action of fibrinogen and / or fibrin is due to joint lubrication, joint protection, and / or joint regeneration.

Accordingly, another example provides a composition for preventing and / or treating a joint or ligament-related disease comprising fibrinogen and / or fibrin as an active ingredient.

The joint or ligament related disease is an inflammation or damage disease of the ligaments located in the joints of the joints such as knees, wrists, ankles, elbows, palms, and toes (eg, degenerative arthritis), fifty shoulders, wrists, ankles, soles, elbows, and the like. Deurevin's disease, plantar fasciitis, tennis elbow, golf elbow and the like.

Fibrinogen and / or fibrin used as an active ingredient in the present invention may be in natural form or artificially synthesized form isolated from the plasma of vertebrates, preferably mammals, such as humans.

In one example, the fibrinogen and / or fibrin may be included in solution form and administered directly to the painful joint, cartilage, and / or ligament site, or lesion site of a joint related disease. Fibrinogen and / or fibrin concentrations in the fibrinogen and / or fibrin solution may be 5 to 100 mg / ml, preferably 10 to 100 mg / ml, and the fibrinogen and / or fibrin may be dissolved in all solvents such as sterile distilled water, The solution may be dissolved in a local anesthetic such as lidocaine or the like as a solvent.

The analgesic effect of fibrinogen and / or fibrin is due to the mechanism of thrombus formation at the site of pain and / or lesions, so as to enhance the analgesic effect of fibrinogen and / or fibrin, for treating the analgesic composition and / or joint-related diseases. The composition may further comprise a substance involved in the formation of one or more thrombi selected from the group consisting of thrombin, calcium, aprotinin and the like. The thrombin and calcium are substances necessary for the process of activating fibrinogen to fibrin, and aprotinin is a substance which slows down the decomposition rate of fibrin formed by inactivating protease. At this time, the amount of thrombin contained per mg of solution may be 25 to 500 i.u, the amount of calcium 1 to 30 mg, the amount of aprotinin may be 100 to 5000 K i.u, but is not limited thereto, and may be appropriately controlled.

Fibrinogen and / or fibrin are already approved for use in the human body for the purpose of suppressing bleeding during surgery, or for supplementing blood fibrinogen in blood, so the harmlessness of the human body has already been demonstrated. Since thrombin, calcium, and / or aprotinin are also approved drugs for the purpose of suppressing bleeding during surgery, they are harmless to humans, and are safe substances that are unlikely to cause abnormalities in humans due to intraarticular cavity injection.

In addition, the analgesic composition of the present invention, or a composition for preventing and / or treating a joint or ligament-related disease, is used in combination with another analgesic drug or a drug for treating a joint-related disease to form a thrombus at the lesion site to delay absorption of the drug. The drug can last longer.

Thus, in another example, the dosage unit of the analgesic composition, or composition for preventing and / or treating a joint or ligament related disease, may be selected from the above-mentioned active ingredients such as fibrinogen (and / or fibrin) or fibrinogen (and / or fibrin). In addition to thrombin, calcium, and / or aprotinin (hereinafter 'thrombin', etc.), it may further include other analgesic drugs or drugs for treating joint-related diseases. The dosage unit may be formulated in one composition with another analgesic drug or joint-related disease treatment drug, in combination with fibrinogen (and / or fibrin) or fibrinogen (and / or fibrin) and thrombin, or with fibrinogen (and / or fibrin) or fibrinogen (And / or fibrin), thrombin, and the like, other analgesic drugs or joint disease treatment drugs may be formulated separately and administered simultaneously, or may be administered sequentially at regular time intervals.

The other analgesic drug, or a joint or ligament-related disease treatment drug, is known to have an analgesic effect or a therapeutic effect on a joint or ligament-related disease (eg, degenerative arthritis, ligament inflammation, ligament injury, etc.) or may have the same effect as above. It includes all drugs expected to be, and may be a steroidal drug, for example, as analgesic drugs include lidocaine, bupivacaine, mepivacaine and the like, dexamethasone, as a therapeutic drug for joint-related diseases, Ketorolac, and the like, but are not limited thereto.

The mode of administration of the composition of the present invention is not particularly limited and may be administered orally or parenterally, but in order to obtain a better analgesic and / or therapeutic effect, a mode of administration applied directly to the pain and / or lesion site, for example, Administration may be by direct injection into pain and / or lesion sites such as articular cavity or ligaments.

The composition may further include appropriate carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions, and may be used in the form of external preparations, such as injections, according to conventional methods.

When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. For example, sterile aqueous solutions, conventional injection solutions, aqueous solvents, non-aqueous solvents, suspension solvents, and the like, for parenteral administration may be included.

The preferred dosage of the composition depends on the condition and weight of the patient, the severity 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. For a more preferable effect, the dosage may be, but is not limited to, administering 1 to 10 ml of a solution having a concentration of 5 to 100 mg / ml of fibrinogen and / or fibrin as an active ingredient.

The dosage may be administered once a day or may be divided several times. The compositions of the present invention can be administered by various routes to an animal, preferably a mammal, including a human. In one embodiment, it may be administered for 3-10 weeks at a frequency of 1-2 times a week.

The present invention proposes fibrinogen, which has proven its biosafety and suitability as an active ingredient for the treatment of pain, such as pain caused by arthritis and / or shoulder ligament injury or joint related diseases, thereby having a superior effect and at the same time safe for the living body. Provided is an agent for the treatment of pain or joint related diseases.

In addition, the fibrinogen has the advantage of forming a blood clot when administered in combination with other analgesic drugs or therapeutic drugs for joint-related diseases, thereby prolonging the duration of effect of these drugs.

The present invention will be described in more detail with reference to the following examples, but the protection scope of the present invention is not intended to be limited to the following examples.

Example : Fibrinogen Effects in Patients with Fifty Shoulders and Knee Osteoarthritis

5 or more cartilage injections (Hyaluronic acid + triamcinolon 10mg + 1% (w / v) lidocaine 3ml / site, intraarticular injection) or inflammatory treatment (1% (w / v) due to symptoms of Rotator cuff injury or osteoarthritis of the knee ) 2ml of fibrinogen solution in which 20mg of fibrinogen (Green Cross, Inc.) was dissolved in sterile distilled water and 3ml of 1% (w / v) lidocaine (Chinese medicine) among patients who did not respond to lidocaine 3ml + Triamcinolon 10mg) After three injections into the same site, three months later, the satisfaction was examined. The results are shown in Table 1 below, and are summarized in Table 2 below.

gender age Pain area Satisfaction F 73 knee +++ F 69 knee ++ F 73 knee + F 54 knee ++ M 70 knee + F 71 knee +++ F 64 knee ++ F 66 knee ++ F 59 knee +++ F 64 knee ++ F 61 knee + F 68 knee +++ F 66 knee ++ M 74 knee +++ F 70 knee + M 80 knee ++ F 70 knee + F 61 knee ++ F 55 knee + F 65 knee ++ M 65 knee + F 51 shoulder ++ M 56 shoulder +++ M 58 shoulder + F 68 shoulder +++ F 72 shoulder +++ F 81 shoulder + M 55 shoulder ++

+ (Less than 25% pain relief)

++ (pain relief less than 25% less than 75%)

+++ (over 75% pain relief)

Pain area Less than 25% pain relief Satisfaction (25-75% reduction) Very Satisfied (Reduced over 75%) knee 7 people 9 people 5 people shoulder 2 people 2 people 3 people

As described above, 21 out of 28 patients showed moderate satisfaction after fibrinogen treatment for the patients who had not been treated with previous pain treatment, and the pain was alleviated in about 68% (66% of knee patients and 71% of shoulder patients). appear.

These results show that fibrinogen is very useful for pain relief such as fifty shoulders and osteoarthritis.

P (k out of n) = n! / k! (n-k)! * (p ^ k) * (q ^ (n-k))

As a result of calculating the binomial probability using the equation, it was confirmed that P = 0.0257 has a significant effect under the effective level of 0.05.

Claims (10)

Painkiller composition comprising fibrinogen, fibrin, or a mixture thereof as an active ingredient. The analgesic composition of claim 1 further comprising one or more selected from the group consisting of thrombin, calcium, and aprotinin. The analgesic composition of claim 1 wherein the fibrinogen, fibrin, or a mixture thereof is in solution at a concentration of 5 to 100 mg / ml. The analgesic composition of claim 1, wherein the pain in which the analgesic composition exhibits analgesic effect is pain due to damage to joints, cartilage, or ligaments. The analgesic composition of any one of claims 1 to 3 formulated in the form of an injection solution injected directly into the pain area. Pharmaceutical composition for the prevention or treatment of joint or ligament-related diseases comprising fibrinogen, fibrin, or a mixture thereof as an active ingredient. The pharmaceutical composition of claim 6, further comprising at least one selected from the group consisting of thrombin, calcium, and aprotinin. The pharmaceutical composition of claim 6, wherein the fibrinogen, fibrin, or a mixture thereof is in solution at a concentration of 5 to 100 mg / ml. The pharmaceutical composition according to any one of claims 6 to 8, wherein the joint or ligament-related disease is arthritis, fifty shoulders, ligament inflammation, or ligament injury disease. The pharmaceutical composition according to any one of claims 6 to 8, which is formulated in the form of injection liquid injected directly into the lesion site of a joint or ligament related disease.