KR20220152904A - Composition for preventing or treating arthritis containing dna fraction and chondroitin sulfate - Google Patents

Abstract

A composition for preventing or treating arthritis containing a DNA fragment derived from Salmonidae fish and chondroitin sulfate (CS) can have excellent pain suppression and cartilage regeneration effects while having rheological properties suitable for injection into a joint.

Description

A composition for preventing or treating arthritis comprising a DNA fraction and chondroitin sulfate

The present invention relates to a composition for preventing or treating arthritis comprising a DNA fraction and chondroitin sulfate.

Osteoarthritis, commonly referred to as degenerative arthritis, is a disease in which articular cartilage surrounding the articular surface of a bone wears out, exposing the bone beneath the cartilage, and inflaming the synovial membrane around the joint, resulting in pain and deformation. Osteoarthritis is the most common chronic disease among joint diseases, and its prevalence in Korea is known to be 5-30% depending on the research method, and tends to increase in proportion to age.

Osteoarthritis is caused by damage to soft cartilage that acts as a buffer between bones. Although the cause is not clear, biomechanical stress of articular cartilage and subchondral bone, biochemical changes in articular cartilage and synovial membrane, and genetic All of these factors are known to be pathophysiologically important (Yunjong Lee. Treatment of osteoarthritis. Journal of the Korean Society of Internal Medicine, 2004, 67.5: 564-567.).

The most common symptom of osteoarthritis is pain in the knee, especially when going up and down stairs. It is known that the degree of pain is worse in the afternoon than in the morning. When osteoarthritis comes to the spine, pain occurs in the back, and in severe cases, tingling nerve symptoms such as a herniated disc may occur. In addition, when osteoarthritis occurs in the hip joint, pain may occur or a range of motion of the joint may be restricted, causing awkward walking. In addition, when osteoarthritis occurs in the knuckles, pain occurs and the knuckles gradually become thicker.

Intra-articular steroid injection can be prescribed as a method for controlling the pain of osteoarthritis, which is more effective in controlling pain that occurs within 4 weeks than chronic pain. The analgesic effect is immediate and the maximum effect appears within 1 week and lasts for about 4 weeks. However, if intra-articular steroid injection is repeated, the cartilage volume may decrease, so there is a disadvantage that frequent prescription cannot be used (Hyung-Young Kim; Yoon-Kyung Seong. Drug treatment of osteoarthritis. Journal of the Korean Medical Association, 2018, 61.10.).

In addition, hyaluronic acid injection into the joint cavity can be tried when pain control with oral medications fails, and the polymer material injected directly into the joint cavity relieves the shock caused by the cartilage tissue lost during the patient's joint movement and helps lubrication. It is known to have a function of improving functional disorders caused by arthritis and suppressing pain. However, hyaluronic acid injections have disadvantages in that the expression of the analgesic effect is very slow and the patient's satisfaction with the treatment is low due to pain when injected into the joint cavity.

Therefore, it is necessary to develop a composition for preventing or treating arthritis, which has an excellent anti-arthritis preventive or therapeutic effect, exhibits a pain relieving effect quickly, and can reduce pain upon intra-articular injection to increase the patient's satisfaction with treatment.

Korean Patent Registration No. 10-1831168

Yunjong Lee. treatment of osteoarthritis. Journal of the Korean Society of Internal Medicine, 2004, 67.5: 564-567. Kim, Hyeong-Young; Yunkyung Sung. Drug treatment of osteoarthritis. Journal of the Korean Medical Association, 2018, 61.10.

According to one embodiment, a composition for preventing or treating arthritis containing a DNA fragment (DNA fragment) and chondroitin sulfate is provided.

One aspect provides a composition for preventing or treating arthritis, including a DNA fragment (DNA fragment) derived from fish of the Salmonidae family and chondroitin sulfate.

The "DNA fragment (DNA fragment)" is a nucleic acid in which one oxygen atom is removed from carbon 2 of ribose, which is the basic structure of nucleic acid, in the form of an extracted biopolymer DNA (Deoxyribonucleic acid) fragment, A mixture of DNA fragments of various molecular weights may be present.

The DNA fraction (DNA fragment) derived from Salmonidae fish has excellent biocompatibility as it is similar to the base composition of humans, and promotes skin healing and tissue regeneration by promoting the production of extracellular matrix (ECM). It is known that it can relieve inflammation at the damaged site and promote the differentiation and growth of chondrocytes.

The Salmonidae fish may be Salmoninae fish, specifically, Oncorhynchus, Salmo, Salvelius, Brachymystax, or Hucho ) may be fish, preferably salmon or trout. It is known that DNA derived from salmonids is known to have superior effects such as skin regeneration and growth promotion than polydeoxyribonucleotides extracted from other fish because it is similar to human base composition.

The DNA fragment derived from Salmonidae fish can be prepared by using a commercially available product or by extracting from testes or semen of Salmonidae fish by a method known to those skilled in the art.

In the present specification, the DNA fragment may be referred to as a DNA fragment.

According to one embodiment, the DNA fragment may include a polynucleotide (PN), a polydeoxyribonucleotide (PDRN), or a combination thereof.

The polynucleotide (PN) and polydeoxyribonucleotide (PDRN) may be classified according to an extraction site, molecular weight, or length. For example, the polynucleotide may be extracted from salmonid fish testis, and the polydeoxyribonucleotide may be extracted from salmonid fish semen. In addition, polynucleotides may refer to those having a relatively larger molecular weight, and polydeoxyribonucleotides may refer to those having a relatively smaller molecular weight. For example, the polynucleotide may have a molecular weight of 1500 to 5000 kDa or 1500 to 10000 kDa, and the polydeoxyribonucleotide may have a molecular weight of 50 to 1500 kDa.

According to one embodiment, the average molecular weight of the DNA fragment is 1,000 kDa to 3,000 kDa, 1,500 kDa to 3,000 kDa, 2,000 kDa to 3,000 kDa, 2,500 kDa to 3,000 kDa, 1,000 kDa to 2,000 kDa to 2,8 kDa to 2,800 kDa, 2,400 kDa to 2,800 kDa.

According to one embodiment, the average length of the DNA fragment may be 1500 to 4600 bp.

According to one embodiment, the DNA fragment may be isolated from the testis or semen of salmonid fish.

The “Chondroitin sulfate (CS)” refers to a glycosaminoglycan (GAG) or mucopolysaccharide composed of D-glucuronic acid, N-acetyl-D-galactosamine and sulfuric acid. The chondroitin sulfate is distributed in matrices, organs, and body fluids of animal connective tissue and is an important structural component of cartilage. The chondroitin sulfate is known to have effects such as inhibition and prevention of adult diseases, antioxidant effect, blood coagulation, inhibition and prevention of arteriosclerosis, protection of joint tissues and inhibition of bacterial infection.

According to one embodiment, the average molecular weight of the chondroitin sulfate may be 5,000 to 70,000 Da, 15000 to 60,000 Da, 15000 to 50,000 Da, 15000 to 40,000 Da, or 15000 to 30,000 Da, but is not particularly limited.

The content of endotoxin in the DNA fragment and the chondroitin sulfate may be 0.025 EU/mg or less, respectively. According to one embodiment, the endotoxin content of the polynucleotide is 0.005 EU/mg or less, and the endotoxin content of the chondroitin sulfate is less than 0.001 EU/mg.

According to one embodiment, the content of DNA fragments in the composition may be higher than the content of chondroitin sulfate. The present inventors have confirmed that, when chondroitin sulfate is added in an amount lower than that of DNA fragments to a composition composed of DNA fragments, complex viscosity, loss modulus, and phase angle suitable for joint injection can be obtained.

According to one embodiment, the composition comprises 2.0 to 4.0% (w / v), 2.0 to 3.5% (w / v), 2.0 to 3.0% (w / v), 2.3 to 2.7% (w / v) of the DNA fragment. v), 2.4 to 2.6% (w/v), or 2.5% (w/v), and the chondroitin sulfate may be included in an amount of 1/4 to 1/3 of the DNA fragment.

According to one embodiment, the weight ratio of the DNA fragment and the chondroitin sulfate is 4:1 to 3:1, 3.8:1 to 3.2:1, 3:7:1 to 3.3:1, or 3.6:1 to 3.4:1 can be

According to one embodiment, the rheological properties of the composition may have a complex viscosity of 10 to 20 Pa s, a phase angle (δ) of 2 to 4 °, and a loss modulus of 10 Pa or more.

According to one embodiment, depending on the contents of the DNA fragment and chondroitin sulfate, it may have rheological properties suitable for administration to joints and exhibit excellent therapeutic effects. The complex viscosity and phase angle may be values measured with a rotational rheometer at 25° C. under a condition of a frequency of 2.5 Hz.

The DNA fragment and chondroitin sulfate may not be cross-linked.

According to one embodiment, the composition may further include NaCl, the content of the NaCl is 0.5 to 1.0% (w / v), 0.5 to 0.9% (w / v), 0.5 to 0.8% (w / v) ), 0.5 to 0.7% (w/v), 0.6 to 1.0% (w/v), 0.6 to 0.9% (w/v), 0.6 to 0.8% (w/v), or 0.6 to 0.7% (w/v) v) can be.

The pH of the composition may be 6 to 8. If the pH is out of the range, the composition may be unstable, and side effects such as pain, swelling, and inflammation may be exhibited when the composition is administered intraarticularly.

According to one embodiment, the composition contains drugs (or active ingredients) known in the art that can help prevent, improve or treat arthritis, as long as they do not inhibit the effect of the composition or cause side effects. can include more. For example, the composition may include at least one selected from the group consisting of antirheumatic agents, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, anesthetics, local anesthetics, immunosuppressants, growth hormones, hormone replacement drugs, and radioactive drugs. may further include.

According to one embodiment, the composition may be an injectable formulation, for example, may be used for intra-articular injection. The injectable formulation may have an average injection pressure of 4 to 28 N, 4 to 15 N, 4 to 10 N, 5 to 10 N, or 5 to 8 N as measured by a tensile strength meter. The "injection force" means the force required when injecting the composition in the form of an injection. In injections for tissue repair, securing appropriate viscoelasticity is important, but excessively high complex viscosity may increase injection pressure, which may cause increased pain for patients. According to one embodiment, it was confirmed that the composition can minimize the patient's pain and increase the convenience of the procedure because the average injection pressure is lower than that of conventional injections.

When the composition is formulated for injection, it may further include pharmaceutically acceptable additives. Examples of the additives include solvents, dissolution aids, buffers, stabilizers, antioxidants, soothing agents, suspending agents, and the like, but are not limited thereto. The amount and type of the additives can be appropriately selected by those skilled in the art within the range that does not affect the stability or efficacy of the active ingredient.

The composition may have an osmotic pressure of 270 to 350 mOsm/kg, preferably 290 to 330 mOsm/kg, and more preferably 290 to 320 mOsm/kg, but is not limited thereto. The osmotic pressure in the human body is about 300 mOsm/kg, and it is ideal for a composition to be injected into the human body to have an osmotic pressure in a range similar to that of the osmotic pressure (or concentration of osmolality) in the body. Side effects may occur. According to one embodiment, the osmotic pressure of the composition is included in the osmotic pressure range of 270 to 350 mOsm / kg, which is ideal for injecting into the body, so it was confirmed that it is suitable for injecting into the body.

The composition may be used for preventing, improving or treating arthritis. The “arthritis” refers to a disease in which articular cartilage is destroyed and inflammatory changes occur in a joint, and may be, for example, osteoarthritis (or degenerative arthritis) or rheumatoid arthritis (RA).

In the present invention, “prevention” refers to any activity in which a disease or abnormal symptom is suppressed or delayed by administration of the composition according to the present invention, and “improvement” means the severity of a disease or abnormal symptom is reduced by administration of the composition according to the present invention. , means all actions that improve or delay the progress, and "treatment" means all actions that improve or cure disease or abnormal symptoms by administration of the composition according to the present invention.

The composition may be for tissue repair or regeneration. The tissue repair or regeneration refers to a mechanism that tries to restore the tissue to its original state when necrosis or defect occurs in the tissue due to trauma or inflammation.

The daily dosage of the composition can be appropriately selected by a person skilled in the art or a skilled physician in consideration of various factors such as age, sex, weight and health condition of the subject, severity, onset time, treatment period, administration route, etc. . The “subject” means an animal including humans and mammals, preferably a human, and more preferably a subject suffering from arthritis or a subject likely to develop arthritis. Subject in the present invention may be used interchangeably with patient.

The composition according to the present invention comprises the steps of i) completely dissolving the DNA fraction, chondroitin sulfate and NaCl in water for injection; And ii) it can be prepared by a manufacturing method comprising the step of sterilization filtration.

A composition for preventing or treating arthritis according to one embodiment may rapidly relieve pain caused by arthritis and have excellent cartilage regeneration effects by including a DNA fragment and chondroitin sulfate.

A composition for preventing or treating arthritis according to one embodiment may have rheological properties such as viscoelasticity suitable for administration to a joint by including DNA fragments and chondroitin sulfate in a predetermined ratio.

The composition for preventing or treating arthritis according to one embodiment has rheological properties suitable for administration to a joint and at the same time has an appropriate osmotic pressure and injection pressure, thereby minimizing the patient's pain and providing excellent procedure convenience. can

The composition for preventing or treating arthritis according to one embodiment may have viscoelasticity similar to that of synovial fluid in the human body by being decomposed in the body after administration to a joint.

Figure 1 shows the results of measuring the storage modulus (G') and loss modulus (G'') of the composition of the present invention.
Figure 2 shows the results of measuring the complex viscosity (η*) of the composition of the present invention.
Figure 3 shows the injection pressure measurement results of the composition of the present invention.
4 shows the result of electrophoresis of the composition of the present invention, and confirms whether chondroitin sulfate can affect the molecular weight of the DNA fraction.
Figure 5 shows the animal efficacy evaluation results, showing the ground tension (weight bearing) test results.

Hereinafter, the present invention will be described in more detail by examples. However, these examples are intended to illustrate the present invention by way of example, and the scope of the present invention is not limited by these examples. In addition, terms not specifically defined in this specification should be understood to have meanings commonly used in the technical field to which the present invention belongs.

Example: Preparation of compositions containing DNA fragments and chondroitin sulfate

Compositions of Examples and Comparative Examples including the compositions shown in Table 1 below were prepared.

For the DNA fragment, HTL biotechnology's medical device grade polynucleotide sodium salt (Polynucleotide sodium salt, medical device grade) product was used. The average molecular weight of the DNA fragments on the catalog was 1000 kDa or more, and the average molecular weight on the test report was 2450 kDa. The content of uracil met the standard of 0.2% or less, the A/T ratio was 0.94 to 1.10, the G/C ratio was 0.85 to 1.19, and the (A+G)/(T+C) ratio was 0.92 to 1.12. met

Chondroitin sulfate (CS) was a chondroitin sulfate product derived from fish cartilage from Maruha-nichiro. The molecular weight was 5,000 to 70,000 Da.

PN (unit: %(w/v)) CS (unit: %(w/v)) NaCl (Unit: % (w/v)) Example 1 2 0.1 0.63 Example 2 2 2 0.63 Example 3 2 5 0.63 Example 4 0.5 2 0.63 Example 5 0.5 0.1 0.95 Example 6 4 0.1 0.63 Example 7 4 5 0.63 Example 8 2.5 0.7 0.63 Example 9 2.5 - 0.63 Comparative Example 1 2 - 0.63 Comparative Example 2 - 2 0.63 Comparative Example 3 BDDE cross-linked HA joint injection (2% hyaluronic acid)

(PN: Polynucleotide, CS: Chondroitin sulfate)

Experimental Example 1. Confirmation of Viscoelasticity Characteristics

The rheological properties of the composition of the present invention were confirmed by analyzing changes in viscosity and elasticity. Specifically, after taking an appropriate amount of the compositions of Examples 1 to 3 and 6 to 8, the storage modulus (G '), loss modulus (G''), complex viscosity (η *) and phase angle (δ) were measured, and the results are shown in Table 2, FIGS. 1 and 2.

<Analysis conditions>

- Test equipment: rotational rheometer (KINEXUS pro, Malvern panalytical company)

- Frequency: 2.5 Hz

- Temperature: 25℃

- Shear strain: shear strain 4

- Measurement gap: 1 mm

The storage modulus relates to elasticity, and the higher the value, the greater the force to return to its original state. The loss modulus relates to viscosity and represents the energy lost when shear stress occurs. In addition, complex viscosity is a result of a complex action of viscosity and elasticity, and is a mathematical expression expressed as the sum of a real part and an imaginary part.

G'(Pa) G''(Pa) Complex viscosity (Pa s) δ(°) Example 1 170.0 5.877 10.78 1.98 Example 2 63.09 5.666 4.013 5.13 Example 3 11.31 3.332 0.747 16.41 Example 6 861.9 37.95 54.66 2.52 Example 7 69.14 13.80 4.467 11.29 Example 8 225.7 13.82 14.33 3.50 Example 9 282.9 8.199 17.93 1.66 Comparative Example 1 168.1 6.033 10.71 2.06

A composition having a complex viscosity range of 10 to 20 Pa·s and a phase angle of 2 to 4° was searched for by varying the concentration and content ratio of PN and CS.

Since the PN and CS were not cross-linked, the complex viscosity was set to 10 to 20 Pa·s higher than the complex viscosity of general synovial fluid (1 to 10 Pa·s) in consideration of the rate of decomposition after injection into the body.

In addition, since the phase angle for maintaining 10 Pa, which is the average loss modulus of synovial fluid in normal joints at the age of 52 to 78 at the range of complex viscosity of 10 to 20 Pa s, is 2 to 4 degrees, the appropriate phase angle range is 2 to 78 degrees. 4. (See Balazs, E.A. (1974). The physical properties of synovial fluid and the special role of hyaluronic acid. In Disorders of the Knee. (Ed. Helfet, A) pp. 63-75)

As can be seen in Table 2, FIGS. 1 and 2, all of the examples except Example 3 exhibited a range of about 1 Pa·s or more, which is the minimum complex viscosity of normal synovial fluid.

In Example 1, the concentration of PN was 2% (w/v) and CS was further added at a concentration of 0.1% (w/v). Example 1 The complex viscosity was 10.78 Pa·s, the storage modulus was 170.0 Pa, and the loss modulus was 5.877 Pa. Compared to Comparative Example 1, which is a commercially available product, Example 1 has the same PN concentration as 2% (w/v), and has similar complex viscosity and modulus of elasticity even though CS is further included by 0.1% (w/v).

Examples 2 and 3 included the same amount of PN as Example 1, and increased the content of CS to 2% (w/v) and 5% (w/v). As a result, the phase angle increased, but the storage modulus, loss modulus, and complex viscosity decreased significantly. In particular, Example 3 had a complex viscosity of 0.747 Pa·s, which was lower than the complex viscosity of normal synovial fluid, 1 Pa·s.

In Example 6, the concentration of PN was 4% (w/v), twice that of Examples 1 to 3, and the content ratio of CS to PN was mixed at 4:0.1. In Example 6, the range of the phase angle was appropriate, but there was a problem that the storage modulus, the loss modulus, and the complex viscosity were excessively increased.

In Example 7, the concentration of PN was set to 4% (w/v), the same as in Example 6, and the content ratio of CS to PN was mixed at 4:5. In Example 7, the complex viscosity was too low and the phase angle was excessively increased.

In addition, when the concentration of PN is 4% (w / v), it takes a long time to dissolve during manufacturing, and it is judged that the economical efficiency is low due to the increase in manufacturing cost due to the increase in raw material concentration.

Accordingly, in Example 8, the concentration of PN was set to 2.5% (w/v), and the content ratio of CS to PN was mixed at 2.5:0.7. Example 8 has a complex viscosity of 14.33 Pa·s and a phase angle of 3.5 degrees, so it was found to have properties suitable for injection into the joint.

Example 9 was prepared with the same PN concentration of 2.5% (v/v) as Example 8 but without CS. Example 9 had a complex viscosity of 17.93 Pa·s and a phase angle of 1.66 degrees, and compared to the physical properties of Example 8, it was found that the loss modulus was low and the range of the phase angle was not appropriate.

In addition, according to the ground tension test of Experimental Example 5 described later, Example 8 containing CS showed a more significant pain relieving effect than Example 9 containing only PN. Therefore, the composition of Example 8 was found to have an excellent arthritis alleviating effect while having physical properties suitable for joint injection. (See Fig. 5)

Experimental Example 2. Investigation of osmotic pressure characteristics

Whether the composition of the present invention is suitable for injecting into the body was confirmed by measuring the osmotic pressure.

Specifically, the osmotic pressure of Examples 2, 4, 5 and 8 was measured using an osmotic pressure meter (OSMOMAT 030-D, Gonotec Co.), and the results are shown in Table 3.

Osmotic pressure (mOsm/kg) Example 2 311 Example 4 296 Example 5 321 Example 8 313

As can be seen from the above results, it was confirmed that the composition of the present invention has an osmotic pressure suitable for injecting into the body, which is included in the range of 270 to 330 mOsm/kg, which is the ideal range of osmotic pressure for internal injections.

In particular, Example 8 was confirmed to have an osmotic pressure suitable for in vivo injection while having a complex viscosity and phase angle suitable for joint injection.

Experimental Example 3. Scanning pressure characteristics investigation

Whether the composition of the present invention is suitable for use for injection was confirmed by analyzing the injection pressure (injection force) through a tensile strength meter, and the results are shown in Table 4 and FIG. 3.

<Analysis condition>

- Equipment: Tensile strength tester (JSV H1000, JISC)

- Measuring range: 10 mm

- Test speed: 30 mm/min

- Needle: 21G

Maximum injection pressure (Unit: N) Average injection pressure (unit: N) Example 1 4.90 4.51 Example 6 14.94 12.77 Example 8 6.87 6.48 Comparative Example 3 29.73 28.70

As can be seen from the above results, compared to Comparative Example 3, which is a hyaluronic acid joint injection crosslinked with BDDE, the composition of the present invention has lower maximum injection pressure and lower average injection pressure, so pain is reduced when administered to a patient and increase the convenience of the procedure.

Experimental Example 4. Electrophoresis

A test solution was prepared by dissolving the compositions of Example 2 (1:1 mixing of PN and CS) and Comparative Example 1 (CS not included) in water so that the concentration of PN was 0.2 mg/ml. An agarose gel was prepared by adding 0.8 g of agarose to a solution of 10 ml of 10X TBE buffer diluted with 100 ml of water, dissolving it while heating, and adding 10 μl of Gel Red while cooling 100 ml of the agarose solution.

After putting 1X TBE buffer in an electrophoresis device (Mupid-exu, Advance), the prepared agarose gel was placed, and 10 μl of the test solution (Example 2, Comparative Example 1 and Comparative Example 2) was loaded with loading dye 2 After uniformly mixing with μl, it was inoculated on an agarose gel.

After inoculating 1 μl of the DNA ladder into another compartment, electrophoresis was performed by applying 100V electricity for 30 minutes, and after completion of the electrophoresis, it was observed under a 160-330 nm UV lamp.

As confirmed in the electrophoresis results of FIG. 4, Comparative Example 2, which does not contain PN, did not show a PN band in the electrophoresis results, and Example 2 and Comparative Example 1 showed the same band as the PN standard. This means that even when PN and CS are mixed, molecular weight change due to mutual binding does not occur, and the physiological effects of each are not lowered. Summarizing the above experimental results, it can be seen that by appropriately mixing PN and CS, synergistic effects suitable for joint injection can be exhibited in terms of physical properties, and at the same time, physiological effects of PN and CS can be exerted in terms of physiology. .

Experimental Example 5. Animal efficacy evaluation

(1) Production of animal models

After hair removal and disinfection around the right knee of a 7-week-old male SD rat, monosodium iodoacetate (MIA) diluted in 0.9% NaCl was administered into the joint cavity of the right knee at 3 mg/50 μl using a 1 mL syringe, followed by administration for 1 week. During breeding, arthritis was induced.

Then, for the animal model inducing arthritis, the area around the right knee was depilated and disinfected, and then the composition of Example 8 (CS added group) or the composition of Example 9 (CS non-added group) was applied 50 μl once using a syringe. Injected. In addition, saline was injected as a control group, and rats in which arthritis was not induced were used as a control group.

(2) Weight bearing test

After administration of the test substance, the weight of the weight carried on both hind legs was measured using an incapacitance tester (Stoelting Co., Wood Dale, IL) once/weekly, and then the value was obtained according to the following formula. Each animal was measured three times, and the average value of each measurement was taken as the individual measurement value.

[formula]

% right hindlimb weight = (right hindlimb weight / (left hindlimb weight + right hindlimb weight)) x 100

According to FIG. 5, the rats administered with the composition of Example 8 showed a more significant pain relief effect than the rats administered with the composition of Example 9. In particular, considering the results from immediately after administration to one week, the composition of Example 8 showed a more rapid pain relief effect than the composition of Example 9.

Summarizing the above experimental results, the composition of the present invention has complex viscosity and phase angle suitable for joint injection, has appropriate osmotic pressure, low injection pressure, low pain, high procedure convenience, and excellent arthritis prevention or treatment effect. point was confirmed.

Claims (13)

A composition for preventing or treating arthritis, comprising a DNA fragment derived from Salmonidae fish and chondroitin sulfate (CS). According to claim 1,
The content of the DNA fragment is higher than the content of the chondroitin sulfate,
A composition for preventing or treating arthritis. According to claim 1,
The composition has a complex viscosity of 10 to 20 Pa s and a phase angle (δ) of 2 to 4 degrees,
A composition for preventing or treating arthritis. According to claim 1,
The composition contains 2 to 4% (w / v) of the DNA fragment,
Comprising the chondroitin sulfate in an amount of 1/4 to 1/3 of the DNA fragment,
A composition for preventing or treating arthritis. According to claim 1,
The weight ratio of the DNA fragment and the chondroitin sulfate is 3: 1 to 4: 1,
A composition for preventing or treating arthritis. According to claim 1,
The average molecular weight of the DNA fragment is 1,000 kDa to 3,000 kDa,
A composition for preventing or treating arthritis. According to claim 1,
The DNA fragment is isolated from the testis or semen of salmonid fish,
A composition for preventing or treating arthritis. According to claim 1,
The DNA fragment is a polynucleotide (PN), polydeoxyribonucleotide (PDRN), or a combination thereof,
A composition for preventing or treating arthritis. According to claim 1,
The average molecular weight of the chondroitin sulfate is 5,000 to 70,000 Da,
A composition for preventing or treating arthritis. According to claim 1,
The composition is a composition for preventing or treating arthritis further comprising NaCl. According to claim 10,
The NaCl content is 0.5 to 1.0% (w / v),
A composition for preventing or treating arthritis. According to claim 1,
The composition further comprises at least one selected from the group consisting of antirheumatic agents, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, anesthetics, local anesthetics, immunosuppressive agents, growth hormones, hormone replacement drugs and radioactive agents. A composition for preventing or treating arthritis. According to claim 1,
The composition is an injectable formulation,
A composition for preventing or treating arthritis.

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