KR20180113475A - a medical composite with the function of both preventing and treating the arthritis and the needle using the composite - Google Patents

Abstract

The present invention relates to a pharmaceutical composition having efficacy for prevention and treatment of arthritis, and more specifically, to a medicinal stuff composition having efficacy for prevention and treatment of arthritis containing Phlomis umbrosa and Eucommia ulmoides and to a medicine needle containing the composition. The present invention provides the medicinal stuff composition having efficacy for prevention and treatment of arthritis, which is extracted by mixing the Phlomis umbrosa and Eucommia ulmoides. The present invention also provides the medicinal stuff composition having efficacy for prevention and treatment of arthritis, which is extracted by adding 500 to 10,000 parts by weight of distilled water to a mixture of 100 parts by weight of the Phlomis umbrosa and 80-150 parts by weight of the Eucommia ulmoides.

Description

[0001] The present invention relates to a pharmaceutical composition having efficacy in the prevention and treatment of arthritis, and a medicament containing the same,

The present invention relates to a pharmaceutical composition having efficacy for prevention and treatment of arthritis, and more particularly, to a composition having efficacy in the prevention and treatment of arthritis, including congestion and bacilli, and a pharmaceutical preparation containing the same.

When rheumatoid arthritis develops, inflammation of various inflammatory cells and chronic inflammatory reaction in the joint occurs, resulting in destruction of cartilage tissue and erosion and deformation of joint bone tissue due to the formation of pannus (Cai L et al., Pathways by which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001, 16 (1): 10-21).

Although the cause of rheumatoid arthritis has not yet been elucidated yet, the continuous inflammatory response due to the action of the major immune response mediators, including the cytokines produced as a result of bioimmune reactions to certain antigenic substances, (Feldmann et al., Role of cystokines in rheumatoid arthritis, Annu Rev Immunol 1996, 14: 397-440).

In particular, inflammatory cytokines such as TNF-, IL-1 and IL-6 have been reported to play a major role in inflammatory responses and joint injuries, and are often found in the joints of patients with rheumatoid arthritis. Injury to the bones of the joint occurs by the invasion of the pannus (de Hooge AS et al., Involvement of IL-6, apart from its role in immunity, in chronic response to experimental arthritis. 6: 2081-2091; Cai L et al., Pathways by interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine 2001, 16 (1): 10-21; Feldmann M et al., Role of cytokines in rheumatoid arthritis, Annu Rev Immunol 1996, 14: 397-440). Pannus is a mass of inflammatory cells that destroys cartilage and damages the cartilage, causing deformation of the joint and also weakening the bone around the joint (Burr DB, The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol. 1998 , 10 (3): 256-262).

In addition, when degenerative arthritis develops, various infiltration of inflammatory cells and chronic inflammatory reaction within the joint occurs, resulting in destruction of cartilage tissue and corrosion and deformation of joint bone tissue due to formation of pannus (Cai L et al., Pathways which interleukin 17 induces articular cartilage breakdown in vitro and in vivo. Cytokine. 2001, 16 (1): 10-21). OA has been recognized as a benign disease that causes chronic degenerative changes in articular cartilage and soft tissue of weight-bearing joints, and accelerates damage by degenerative changes. However, recent studies on the pathogenicity factors of OA have been actively carried out due to the recognition of the genetic factor, the personal or social environment, and the development of new research techniques. (Haq Iet al., J. Osteoarthritis, Postgrad Med J. 2004, 79 (933) 377-383.)

Such medicines for prevention and treatment of rheumatoid arthritis or degenerative arthritis are widely used. However, since these medicines have side effects that give toxicity to the liver, there have been many developments in the prevention and treatment of arthritis using herbal medicines.

In a patent application No. 10-1235238 ("Veterinary extract having excellent therapeutic effect against degenerative arthritis, and pharmaceutical composition containing the same", hereinafter referred to as "Prior Art"), "a method of activating the proliferation of chondrocytes by containing a hot- Lt; RTI ID = 0.0 > a < / RTI > pharmaceutical composition for treating degenerative arthritis.

The above-described prior art and natural extract compositions of the prior art still have insufficient efficacy in the prevention and treatment of arthritis. Accordingly, the present invention provides a pharmaceutical composition having efficacy for prevention and treatment of arthritis without toxicity and no side effects do.

The present invention also provides a medicament comprising a medicinal composition which is effective for the prevention and treatment of arthritis which is free from side effects and which is free from toxicity which can act directly on the site of arthritis.

In order to solve the above problems and needs,

The present invention provides a medicinal composition which is effective for prevention and treatment of arthritis which is extracted by mixing a genus and a mite.

In addition, the present invention provides a pharmaceutical composition having an efficacy for preventing and treating arthritis, which is obtained by mixing 80 to 150 parts by weight of bamboo shoots in 100 parts by weight of a speed step and 500 to 10,000 parts by weight of distilled water.

The present invention also provides a medicament comprising the above medicinal composition.

The pharmaceutical composition having the efficacy in the prevention and treatment of arthritis according to the present invention has a higher effect than the natural extract composition of the prior art and prior art, and has no side effects even without toxicity.

In addition, the pharmaceutical composition and the medicinal herb which are effective in the prevention and treatment of arthritis according to the present invention have a remarkable effect in the prevention and treatment of arthritis because they have a function of directly acting on the site of arthritis.

FIG. 1 is a graph showing the effect of the amount of Matrix metalloproteinase-9 (MMP-9) on the serum of an MIA-induced arthritic rat administered with the pharmaceutical composition of the present invention.
FIG. 2 is a graph showing the effect of LTB _{4 on} the serum of MIA-induced arthritic rats administered with the pharmaceutical composition of the present invention.
FIG. 3 is a graph showing CTX II production effect of serum of MIA-induced arthritic rats administered with the pharmaceutical composition of the present invention.
FIG. 4 is a graph showing the calcitonin effect of serum of MIA-induced arthritic rats administered with the pharmaceutical composition of the present invention.
FIG. 5 is a graph showing the Glycosaminoglycan effect of serum of an MIA-induced arthritic rat administered with the pharmaceutical composition of the present invention.
FIG. 6 is a graph showing the effects of the foot weight measurement of the MIA-induced arthritic rats administered with the pharmaceutical composition of the present invention.
FIG. 7 is a graph (front view) of frontal and lateral views of a knee joint of an MIA-induced arthritic rat administered with the pharmaceutical composition of the present invention using micro CT.
FIG. 7b is a graph (side view) of a frontal and lateral views of a knee joint of an MIA-induced arthritic rat administered with a pharmaceutical composition of the present invention using micro CT.
FIG. 8 is a graph showing the results of H & E staining of knee joints of MIA-induced arthritic rats administered with the pharmaceutical composition of the present invention.
FIG. 9 is a graph showing the Safranin-O staining of the knee joint of an MIA-induced arthritic rat administered with the pharmaceutical composition of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS FIG.

The present invention provides a medicinal composition having efficacy in the prevention and treatment of arthritis which is extracted by mixing a genus and a bacterium, and a medicament containing the medicinal composition.

The present invention provides a medicinal composition having efficacy for preventing and treating arthritis which is extracted by adding raw materials mixed with the above-mentioned speed and bacterium to distilled water, and a medicinal herb containing the medicinal composition.

The above-mentioned medicament means a form containing the pharmaceutical composition of the present invention and having a function of injecting through the skin since it is in the form of a syringe.

In the present invention, it is possible to obtain a pharmaceutical composition by mixing 80 to 150 parts by weight of a mixture of 100 parts by weight of the compound and 500 to 10,000 parts by weight of distilled water.

Preferably, it is effective to obtain a pharmaceutical composition by mixing 1,300 to 2,000 parts by weight of distilled water with 100 parts by weight of a mixture of 90 to 110 parts by weight of the mixture.

The above-mentioned herbaceous plant of the present invention is a medicinal herb made from roots of Dipsacus asperoides C. Y. Cheng et T. M. Ai (Korea). In China, plants like Korea are used. In Japan, it was not found in process medicines.

The meaning of the term (續 断) means that the bones are broken. It is also called "字 折" and "골 骨", all of which are attached according to efficacy.

This medicine has a slightly fragrant smell, taste is very high, and the quality is slightly warm. [苦辛 微 温]

The hereditary gland shows the liver and the gland. It strengthens the muscles and connects the blood vessels to the back and knees. It is used for pain, sickness, arthritis and joint fatigue. It can also be used for pain due to premature ejaculation, oil wells, anemia, hypertrophy and ejaculation due to sexual dysfunction.

Alkaloids, essential oils and vitamins have been reported as pharmacological actions.

The above-mentioned two species of the present invention refers to a medicinal substance (Korea, China, Japan) of bark of Eucommia ulmoides Oliver.

In Korea, it is used to read and write Chinese characters, but China and Japan are written as 杜 冲. This is the name given to people who used to eat and drink this medicine in the old days, and the tongue called "四 仲 仲" and "四 仙" came from the same story. Quercus mongolica is often called cotton because it has a lot of transparent fibers like silk in leaves and bark.

The taste of this medicine is very sweet and its quality is warm. [甘辛 溫]

There is an effect of lowering blood pressure by treating low back pain due to lack of function of liver (kidney), knee pain, numbness of body, coldness of lower abdomen, urinary frequency, early anxiety, uterine bleeding.

Antihypertensive action, anti-aging, cholesterol lowering, anti-inflammation, sedation, pain relief, immune control, blood clotting, uterine contraction, antiallergic and antibacterial activity have been reported.

In the present invention, a raw material mixture in which 500 to 10,000 parts by weight of distilled water is mixed with 80 to 150 parts by weight of double helix in 100 parts by weight of the speed is connected to a distillation apparatus, and the mixture is heated at an extraction temperature of 140 to 160 ° C., And is extracted at a temperature of 15 ° C until it is added to 95 to 105 parts by weight for 0.5 to 2 hours.

More preferably, 100 parts by weight of a mixture of 100 parts by weight of the raw material and 100 parts by weight of two kinds of raw materials are mixed in 1500 parts by weight of distilled water. The raw material mixture is heated and connected to a distillation apparatus. Lt; RTI ID = 0.0 > 100 parts < / RTI > by weight.

In the present invention, a glass fiber filter (GS-25) is connected to an inhaler, a distillate extracted therefrom is injected to remove foreign substances, a syringe and a syringe (10 cc) in a vial using a syringe filter (DISMIC-25CS), covered with rubber caps and aluminum caps, and sterilized.

The present invention provides a medicament composition containing the above-described medicinal composition in a syringe, which is effective for preventing and treating arthritis.

The above-mentioned medicinal herbs can directly prevent arthritis from arthritis, and can prevent and treat arthritis more effectively.

The pharmaceutical composition of the present invention having the above-described constitution has a remarkable effect on prevention and treatment of arthritis.

<Examples>

Ⅰ. Pharmaceutical composition manufacturing

In the present invention, 95 g (95 g to 105 g) of water are added to a reaction vessel containing 15 g of a gentle-phase and 15 g of bivalve in 220 ml of distilled water, heated and connected to a distillation apparatus at an extraction temperature of 150 ° C. and a cooling water temperature of 10 ° C. for 1 hour, To be extracted.

The glass fiber filter (GS-25) was connected to a suction unit, the distilled extract was injected therein to remove foreign substances, and the extracted foreign substance was filtered through a syringe and a syringe filter (10 cm3) using a syringe filter (DISMIC-25CS) and sterilized by covering with a rubber pad and an aluminum cap to obtain a pharmaceutical composition.

The medicinal composition obtained above was put into a syringe to prepare a medicament. In the present invention, the medicament in which the medicinal composition is injected into the syringe is called a KV pharmacopuncture (KV).

Ⅱ. Animal experiment

1. Animal arthritis induction

1) Animal and feed

The animals were fed a Harlan 2018S rodent diet (USA) solid diet and water until the day of the experiment and were maintained at a temperature of 22 ± 2 ° C , Humidity 55 ± 15%, and light-dark cycle (12 hours) for 2 weeks. This experiment was conducted in accordance with the animal ethics code of the Animal Experimental Ethics Committee of the Great War of the Worlds (approval No. DJUARB 2016-018).

2) Arthritis induction

After 2 weeks of adaptation period, rats were anesthetized with anesthetics (0.4 ml of ketamine + 0.1 ml of rimpung), and the vicinity of the right knee joint was cleaned. Then, MIA, which is an osteoarthritis inducing substance, was administered to a diabetic syringe (BD Ultra- Fine II Insulin Syringe: BD Medical- Diabetic Care, USA) was used to administer 50 ㎕ of 60 ㎎ / ㎖ in the right knee joint, and physiological saline (0.9% saline) was used for MIA dilution.

 3) Experimental group  Classification and medication administration

The experimental groups were divided into three groups: normal group without arthritis, control group with saline alone, and KV group (KV). Group animals were divided into three groups Six groups were classified per group.

We administered 50 μL of diabetic syringe (KVJ) at 10:00 am on the right side of the stomach (BL40) for 1 week after the injection of arthritis inducer. The duration of the experiment was 4 weeks.

2. Experimental results

1) Arthritis oil factor measurement

After the end of the experiment, heart blood was collected and centrifuged at 3,000 rpm for 15 minutes. The serum was measured as follows.

(1) Production of Matrix metalloproteinase-9 (MMP-9)

50 μl of each standard, control, and serum sample was added to a 96-well plate and mixed using a plate shaker for 2 hours. After washing, 100 μl of Total MMP-2 Conjugate was added and mixed again on a plate shaker for 2 hours. After washing again, 100 μl of substrate solution was added, and incubated for 30 minutes at 37 ° C in an incubator with blocking of light. 100 μl of stop solution was added to the solution and measurement was carried out at 450 nm wavelength using an ELISA reader. The measured values were calculated using the 4 parameter logistic curve-fit as a percentage based on the control group.

After the end of the experiment, the amount of MMP-9 produced in the serum was found to be 68.2 ± 9.5% in normal group and 73.6 ± 1.2% in normal group when the control group was 100.0 ± 4.4%, and KV was significantly decreased compared to the control group (Fig. 1).

(2) Production of Leukotriene B4 (LTB ₄ )

50 μl of standard and serum samples were added to a 96-well plate, and 50 μl of primary antibody solution was added, followed by mixing for 1 hour using a plate shaker. Then, 50 μl of LTB ₄ conjugate was added and mixed again on a plate shaker for 3 hours before washing. After adding 200 μl of substrate solution, incubate for 30 minutes at 37 ° C in a light incubator. Add 100 μl of stop solution and measure at 450 nm wavelength with ELISA reader. The measured values were calculated using the 4 parameter logistic curve-fit as a percentage based on the control group.

After the end of the experiment, the amount of LTB ₄ produced was 80.6 ± 8.4% in the normal group and 81.1 ± 7.4% in the normal group when the control group was 100.0 ± 3.7%, and KV was significantly decreased compared to the control group 2).

(3) C-Terminal Telopeptides of Type II Collagen (CTX Ⅱ) and Calcitonin, glycosaminoglycan production

50 μl of each standard, control, and serum samples were added to a 96-well plate, and 100 μl of HRP-conjugate reagent was added, followed by incubation for 1 hour in an incubator. After washing, 50 ㎕ of chromogen solution A and B were sequentially added, reacted in an incubator for 15 minutes, and 50 ㎕ of stop solution was added and measured at an ELISA reader wavelength of 450 nm. The measurement results were calculated by using log-log fit as a percentage based on the control group.

1) After the end of the experiment, the amount of CTXII produced in the serum was 100.0 ± 14.2%, 100.4 ± 17.6% and 57.7 ± 9.3%, respectively, and the KV was significantly decreased compared with the control group 3).

② After the end of the experiment, the amount of calcitonin produced was 126.2 ± 11.7% in the normal group and 123.5 ± 7.0% in the control group, and the KV was significantly increased compared to the control group (100.0 ± 8.4% 4).

③ When glycosaminoglycan production was measured at the end of the experiment, KV was significantly increased in the control group as compared with the control group as 216.0 ± 7.6% and 172.6 ± 5.9% in the normal group and 100.0 ± 4.6%, respectively 5).

 5) Foot weight measurement

(1) Rear weights were measured using an Incapacitance Test Meter before the end of the experiment, and the intensity applied to each hind paw was averaged over a 10-second period. The calculated results were calculated by using the following equation (Table 1) and then expressed as a percentage based on the control group, as the percentage of body weight distributed in the right hind paw causing arthritis.

Weight bearing ratio (%) = ( Weight of induced lower limbs ) × 100 Weight of normal leg

(2) The weight of the hind paw before the end of the experiment was 209.5 ± 31.0% in the normal group and 149.1 ± 18.1% in the normal group when the control group was 100.0 ± 31.1%, and the KV was significantly increased compared to the control group (Fig. 6).

6) Micro-CT

After the end of the experiment, 3 mice were randomly selected from the group of animals that had undergone the experiment, and they were asked to Dongguk University (Ilsan Campus) to convert the front and side images to 3D to read the cartilage area.

As a result of photographing the frontal and lateral views of the knee joint using micro CT, it was confirmed that the catilage volume of the control group and the herbicide group was significantly reduced compared to the normal group. However, More preserved. In the control group and the herbicide-treated group, the lower end of the femoral bone was more eroded and destroyed than the normal group, but the herbicide-treated group showed less corroded or destroyed bone (Figs. 7A and 7B).

7) Histopathological examination

Micro-CT was performed, and 3 left knees of the remaining group were excised and fixed in formalin. Then, H & E staining and Safranin-O staining were applied to OptiParm. Then, the state of the tissue was observed through an optical microscope through a dye slide.

(1) H & E dyeing

As a result of H & E staining of the knee joints, it was found that the catilage between the femur and tibia was significantly reduced in the control group and the control group compared to the normal group, The amount was further preserved. In addition, it was confirmed that the infiltrative cells (Infiltrative cells) were formed in the vicinity of the cartilage in the control group and the medicament-administered group, but the range and density of the infiltrating cells were relatively smaller in the medicament-administered group than in the control group (FIG. 8).

(2) Safranin- O staining

As a result of the Safranin-O staining of the knee joint, the control group and the herbicide-treated group formed the reddish-dyed proteoglycan in the periphery of the cartilage and the synovial membrane, but the control group was proteoglycan (Fig. 9). In contrast, the drug-treated group showed a greater distribution of proteoglycan around the cartilage and synovial membrane (Fig. 9).

It can be seen that the present invention has remarkable efficacy in the prevention and treatment of arthritis as shown in the above examples and experimental results.

INDUSTRIAL APPLICABILITY The present invention is very useful in an industry that researches, produces, processes, distributes and sells functional foods and medicines, which have remarkable efficacy in the prevention and treatment of arthritis using herbal medicines and herbs.

Claims (2)

A medicinal composition having efficacy in the prevention and treatment of arthritis which is extracted from a mixture of genus and mites.
A pharmaceutical formulation comprising the pharmaceutical composition of claim 1.

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