JP5279946B1 - Joint pain remedy - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new joint pain improving agent for alleviating joint pain due to osteoarthritis or the like.
SOLUTION: An active ingredient is a plant body of a button bowfish (Peucedanum japonicum Thunb. Var. Japonicum) and its related plants and / or an extract thereof, particularly an extract by water, and other excipients and bindings necessary for pharmaceutical preparations. Additives such as agents and disintegrants are added to form pharmaceutical compositions and so-called foods for specified health use. In addition, an effective amount of an extract is added in the production of foods for general use to obtain foods that have an effect of improving joint pain.
[Selection figure] None

Description

  The present invention relates to an agent for improving arthralgia.

  In advanced countries, the aging of the population has progressed year by year. In Japan, there are currently 42.6% of households with people over the age of 65, and about 50% of those over the age of 65 have some subjective symptoms. (2010 National Life Basic Survey / Ministry of Health, Labor and Welfare). Specific subjective symptoms include joint pain, stiff shoulders, and back pain, which are ranked high in both men and women. With the aging of the population, the number of people requiring support / care needs has also increased, but when looking at the main causes according to the level of care required, “joint diseases” (19.4%) ranked first among those requiring support. (Summary of 2010 “Basic Survey of National Life”, Ministry of Health, Labor and Welfare), “Joint Pain” is presumed to be a major factor in lowering QOL. In other studies, the number of knee osteoarthritis patients in Japan is approximately 10 million with subjective symptoms and approximately 3,000 with potential patients (number of patients by X-ray diagnosis). It is estimated that there are 10,000 people.

  Osteoarthritis is a typical joint disease. Osteoarthritis of the knee is a disease in which the cartilage of the joint is worn due to multiple factors such as aging and exercise, abuse, injury, and cartilage deformation, meniscus tear, and ligament damage. In early stages of pain, cartilage is worn and cartilage is damaged, but if meniscus tear or ligament damage progresses, the hyaluronic acid concentration in the joint decreases, resulting in joint smoothness. You will lose more. Although there are individual differences in symptoms, the symptoms at the knee often appear prominently, and the posture of starting to walk on the knee, ascending / descending the stairs, sitting down and squatting gradually becomes difficult. Furthermore, as the disease progresses, stiffness of the knees and severe pain when waking up may occur, and in severe cases, walking may become difficult. Inflammation may also occur as cartilage damage, meniscal tears, and ligament damage progress.

  For joint pain accompanied by such wear and deformation of cartilage, conservative treatment such as drug therapy and exercise therapy and surgical treatment by surgery are performed. Regarding pharmacotherapy, in addition to the use of analgesics for temporary symptom relief, nonsteroidal anti-steroids that suppress the production of the analgesic substance prostaglandin E2 (PGE2), that is, have a cyclooxygenase (COX) inhibitory action. Inflammatory drugs (NSAIDs) are prescribed. In addition to this, for the purpose of smoothing the joint, hyaluronic acid is locally injected, and oral medications mainly composed of glucosamine, chondroitin sulfate, and collagen are widely used. In addition, a composition comprising several kinds of herbal medicines such as Bushi and Bukuryu, a composition obtained by adding glucosamine to this composition (see Patent Document 1), and a composition comprising several kinds of herbal medicines such as Bakumontou, Toki and Hange (see Patent Document 2). Attempts have been made to improve joint pain. However, the use of such a composition, glucosamine, and chondroitin sulfate is not sufficient for improving joint pain, and a new improving agent is required.

  By the way, it is publicly known that button pea (Peucedanum japonicum Thumb. Var. Japonicum) is used as a folk medicine, and its roots and leaves are effective for so-called cold symptoms and nutritional tonic (see Non-Patent Document 1). In addition, button fountain has a NO production inhibitory action (see Patent Document 3), a COX inhibitory action (see Non-Patent Document 2), a cell activation action and a melanin production inhibitory action, and an antioxidant action (see Patent Document 4), acyl. CoA cholesterol acyltransferase (ACAT) inhibitory action (see patent document 5), prostacyclin production promoting action (see patent document 6), blood flow and fat metabolism promoting action (see patent document 7), skin transparency increasing action ( (See Patent Document 8). However, so far, there is no known report that button bow fu clinically improves joint pain.

JP 2006-176460 A JP 2011-251934 A JP 2008-273978 A JP 2004-026697 A International Publication WO2006 / 082743 JP 2005-350432 A JP 2008-1000095 A2 JP 2011-184358 A

Kazuo Izawa, Herbal Color Dictionary, Housewife's Friend, 1998, p516 MingShan Zheng, et al., Korean J. Medicinal Crop Sci., 13,75-79,2005

  An object of the present invention is to provide a novel composition effective for joint pain.

  The inventors of the present application have studied the button bow so as to find out that the button bow is effective for joint pain, and have completed the present invention. That is, the joint pain ameliorating agent according to the present invention contains, as an active ingredient, plant bodies of botanical fufu and related plants and extracts thereof.

  According to the present invention, a novel joint pain improving agent is provided.

  The joint pain ameliorating agent according to the present invention contains, as an active ingredient, a plant body and / or an extract of a close-up plant of buttoned cucumber (Peucedanum japonicum Thunb. Var. Japonicum).

  In the present specification, joint pain is pain to be remembered in a joint, and is mainly caused by wear of joint cartilage due to factors such as aging, overuse of exercise, injury, etc. as typified by osteoarthritis. Means pain associated with joint disease. The joint diseases include diseases accompanied by inflammation, and the joint pain improving agent according to the present invention is effective against joint pain accompanied by inflammation. It is characterized in that it improves pain that occurs in the skin. In this regard, Patent Document 3 suggests that the NO production-producing agent may be effective against inflammatory diseases such as rheumatoid arthritis, but the joint pain improving agent according to the present invention. Is effective even if it is not an inflammatory joint disease such as rheumatoid arthritis or infectious arthritis. Further, Non-Patent Document 1 suggests that button fountain has a COX inhibitory action and an anti-inflammatory action, but the active substance is a coumarin compound obtained from an extract with chloroform. On the other hand, the active ingredient of the improving agent of the present invention is mainly contained in the extract by water, and is considered to have a different active body from the anti-inflammatory action of Non-Patent Document 1. Furthermore, as shown in the examples, improvement of joint pain has been observed for anti-inflammatory agents, anti-inflammatory analgesics, and those who have not been effective in so-called health foods that have an anti-inflammatory effect. The mechanism of action of the joint pain ameliorating agent according to the invention is considered to be different from the NO production suppressing action and COX inhibiting action as described above.

  That is, the joint pain improving agent of the present invention is a non-inflammatory joint other than inflammatory joint pain caused by diseases such as joint pain associated with influenza infection, and diseases such as collagen disease, spondyloarthritis, infectious arthritis, gout and rheumatoid arthritis. For pain. However, cases involving inflammatory joint pain are also included. Non-inflammatory arthralgia includes arthralgia resulting from neuropathic arthropathy and so-called neuralgia, both of which are caused by abnormalities in the peripheral nerves. Thus, the mechanism of action of the joint pain improving agent of the present invention is considered to be different from the mechanism of action of the neuralgia improving agent.

  The button bow (Peucedanum japonicum Thunb. Var. Japonicum) used in the present invention is an evergreen perennial plant of the genus Apileae (Apiaceae). It is distributed in the archipelago, southern Korea, China, and the Philippines, and grows naturally under severe natural conditions such as coastal cliffs and rocks. In Okinawa, it is also known as Chomeigusa or Sakuna.

  In the present invention, button buds and their related plants and / or extracts of these plants are used as active ingredients. In the present invention, any part of the plant body such as roots, leaves, stems and flowers is used, but leaves are preferably used.

  In the present invention, the plant is a raw plant and may be a dried plant (dried product). Furthermore, the plant body which cut | disconnected these and the pulverized plant body may be sufficient. From the viewpoints of dosage and dosage form, dried plants and plant extracts are preferably used.

  The dried product is produced by a general method used for drying plants such as natural drying, freeze drying, and drying using heat. Moreover, what further cut | disconnected and grind | pulverized the dried material is used preferably.

  The extraction is also performed by a general method used for producing a plant extract. For example, there is a method in which an extraction solvent is added to a raw or dried plant body, immersed in a room temperature or while heating, and the plant body as a residue is separated by filtration or centrifugation to obtain a leachate. The extraction solvent is not particularly limited as long as improvement of joint pain is expected, and any of a hydrophilic solvent (polar solvent) and a hydrophobic solvent (nonpolar solvent) may be used. The terms hydrophilic solvent (polar solvent) and hydrophobic solvent (nonpolar solvent) are used in the meaning commonly used by those skilled in the art, and the hydrophilic solvent is, for example, water, methanol, ethanol, propanol (Both linear and branched), butyl alcohol (regardless of linear and branched), 1,3-butylene glycol, 1,3-butanediol, glycerin, etc. It can be a monohydric alcohol. The lipophilic solvent is, for example, hexane, ether, and chloroform. The solvent may also be a mixed solvent in which two or more solvents are mixed at an appropriate ratio, such as a mixed solution of water and ethanol. From the viewpoint of the effect, the extraction solvent is preferably a hydrophilic solvent, and particularly water or a mixed solution of water and ethanol is preferable. The form of the extract is not particularly limited, and may be, for example, the obtained extract itself, or a semi-solid or solid obtained by applying a treatment such as concentration or lyophilization.

  The joint pain ameliorating agent according to the present invention is not only the extract itself, but if necessary, excipients, disintegrants, dispersants, binders, stabilizers, gelling agents, preservatives, colorants, pH adjustment Additives necessary for formulation such as agents, flavoring agents and emulsifiers.

  The form of the joint pain ameliorating agent according to the present invention is not particularly limited as long as it can be taken, and it is liquid, solid like a tablet, powder, granule, paste, gel, capsule, syrup, etc. Is exemplified. For these forms, an effective amount of the extract and necessary additives may be mixed to prepare the required form. In addition, for these forms, the extract and the necessary additives may be mixed in one step to mix the extract in the composition, or, for example, two types including the extract in advance An extract may be contained in the composition in two or more steps such as preparing granules and mixing them.

  The joint pain improving agent according to the present invention can be provided not only as a pharmaceutical composition but also as a so-called health food. In particular, it is preferably used for the use of a food for specified health use that can be labeled as effective for improving joint pain.

  The joint pain ameliorating agent according to the present invention is also provided as a form of food or drink by directly mixing an effective amount of the extract with various foods or drinks or mixing with other raw materials in the process of producing the food or drink. The form of food and drink is not particularly limited. Examples of foods and beverages include vegetable drinks, fruit juice drinks, soft drinks such as tea, dairy products such as yogurt and milk, cakes, cookies, candy, gummi, gum, manju, sheepskin and other Japanese and Western sweets, drinks, etc. Nutritional supplements.

  The intake of the joint pain ameliorating agent according to the present invention is appropriately increased or decreased depending on body weight, age, sex, symptom, dosage form and the like. The lower limit of the daily intake is, for example, 0.001 g, 0.01 g, 0.1 g, and 0.3 g as an extract. Moreover, the lower limit amount is 0.01 g, 0.1 g, 1 g, 2 g, 5 g, and 10 g in terms of bulk drug substance (dry product). Preferably it is 0.2-0.3g or more. The upper limit of intake is 5 g, 2 g, 1 g, and 0.5 g as an extract. Moreover, the upper limit is 50g, 20g, 15g, 10g, and 5g in the raw material conversion (dry substance).

  The joint pain improving agent according to the present invention optionally contains one or more compounds selected from the group consisting of glucosamine, chondroitin sulfate and salts thereof, hyaluronic acid and collagen. The salt of chondroitin sulfate is a pharmacologically acceptable salt and can be, for example, a sodium salt. The compounding amount of these compounds is also appropriately increased or decreased depending on body weight, age, sex, symptom, dosage form and the like. The lower limit of daily intake is 0.001 g, 0.01 g, 0.1 g, 1 g, 2 g, and 5 g. In addition, the blending ratio with button fountain is arbitrary, and it may be greater or less than the blending amount of button fountain, and the blending amount of optional ingredients such as glucosamine is equivalent to the drug substance (dry matter) ) From 0.0001 to 10,000 (mass ratio).

  Next, the present invention will be described in more detail based on the following examples. Needless to say, the present invention is not limited to the following examples.

<Production Example 1>
The raw button leaf was dried, water (10 kg) was added to the obtained dried leaf (1 kg), and the mixture was extracted by stirring at 80 ° C. for 2 hours. Thereafter, the filtrate was collected by filtration and centrifugation, and further concentrated under reduced pressure. This was pulverized after freeze-drying to obtain a powdered button bow extract (350 g).

<Production Example 2>
The raw button leaf was dried, water (100 kg) was added to the obtained dried leaf (10 kg), and the mixture was extracted by stirring at 80 ° C. for 2 hours. Thereafter, the filtrate was collected by filtration and centrifugation, and further concentrated under reduced pressure. To this was added 1.5 kg of Paindex # 2 (manufactured by Matsutani Chemical Co., Ltd.), and the mixture was homogenized after stirring and dissolving. This was spray-dried to obtain powdered button bow extract extract (4.5 kg).

<Production Example 3 / Prescription 1 (Tablet)>
Based on the formulation shown in Table 1, tablets were prepared by a conventional method.

<Production Example 4 / Prescription 2 (Tablet)>
Based on the formulation shown in Table 2, tablets were prepared by a conventional method.

  For the 20 males and females 40 years of age or older who have subjective symptoms of knee joint pain (including subjects who have pain symptoms at multiple sites such as waist, shoulder, wrist, etc. in addition to knees) A 4-week ingestion test was conducted using The intake per day is 100 mg as a button fountain extract, and 285.7 mg dried button fountain in terms of active ingredient. Table 3 shows a breakdown of the subjects. Each subject was not afflicted with diseases such as influenza, joint disease, spondyloarthritis, infectious arthritis, gout, rheumatoid arthritis, etc. due to causes other than cartilage wear.

  The effect on knee pain was evaluated by the knee osteoarthritis function evaluation scale (JKOM: Japan Knee Osteoarthritis Measurement). In JKOM, I.I. Degree of pain (VAS: Visual Analogue Scale), II. Pain and stiffness, III. State of daily life, IV. Daily activities, etc. Although it is divided into five categories of health status, a total value was obtained for each category, and score change before and after intake was evaluated as an effect index (degree of improvement). All obtained scores were expressed as mean ± standard error. The usefulness evaluation by comparison before and after ingestion was performed by a paired t-test. The significance levels were 1%, 0.5%, and 0.1%, respectively indicated by “*”, “**”, and “***”. All statistical processing used Excel (Microsoft) functions and analysis tools. The results are shown in Table 4.

  The effect on pain other than the knee was evaluated by a questionnaire to the subjects. Specifically, in response to the question “Is there any effect on pain?”, I was asked to answer either “effective or ineffective”.

  As a result of JKOM evaluation, I. degree of pain (VAS), II. Pain and stiffness, III. Status of daily life and V. It showed a significantly low value in the health state, and the improvement effect on the pain of the product of the present invention was confirmed.

  Furthermore, in the questionnaire results, some subjects who felt pain in the lower back, shoulders, elbows, and wrists also responded “effective” and were effective against pain other than knees. Was confirmed.

  In addition, subjects who evaluated improvement in JKOM evaluation or questionnaire results were formulated with anti-inflammatory agents or anti-inflammatory analgesic compresses (4 persons) and anti-inflammatory materials (such as Western willow extract and cat's claw). There were also subjects who had no effect on pain when using health foods (3 people) (the use during the study period was avoided). From these results, it was considered that the effect of the product of the present invention on the pain of joint pain was exerted by an action mechanism different from the anti-inflammatory action.

  For Production Example 4 for 33 men and women aged 40 years or older who have subjective symptoms of knee pain (including subjects with pain symptoms in multiple areas such as waist, hip joint, shoulder, wrist, etc. in addition to knees) A 2-week ingestion test using tablets was performed. The daily intake is 300 mg as a button fountain extract, and about 1000 mg of dry button fountain in terms of the active ingredient. The breakdown of the subjects is shown in Table 5. Each subject was not afflicted with diseases such as influenza, joint disease, spondyloarthritis, infectious arthritis, gout, rheumatoid arthritis, etc. due to causes other than cartilage wear.

  The effect on knee pain and pain at other sites was evaluated according to the method described in Example 3. At this time, the significance levels were 1%, 0.1%, and 0.01%, respectively indicated by “*”, “**”, and “***”. All statistical processing used Excel (Microsoft) functions and analysis tools. The evaluation results by JKOM are shown in Table 6.

  As a result of JKOM evaluation, I.V. Degree of pain (VAS), II. Pain and stiffness, III. Status of daily life and V. It showed a significantly low value in the health state, and the improvement effect on the pain of the product of the present invention was confirmed.

    Furthermore, in the questionnaire results, some subjects who felt pain in the lower back, shoulders, elbows, and wrists also responded “effective” and were effective against pain other than knees. Was confirmed.

  From the above tests, it was confirmed that joint pain was improved early by taking the joint pain ameliorating agent according to the present invention.

  The joint pain ameliorating agent containing the button fountain extract according to the present invention is expected to significantly improve joint pain when taken for a short time. Therefore, it can be widely used as a medicine or food for the purpose of treating or improving joint pain.

Claims (3)

A non-inflammatory joint pain ameliorating agent comprising a water extract of button cucumber (Peucedanum japonicum Thumb. Var. Japonicum) as an active ingredient.   The improving agent according to claim 1, comprising one or more compounds selected from the group consisting of glucosamine, chondroitin sulfate and salts thereof, hyaluronic acid, and collagen. A method for producing a composition having an action of improving non-inflammatory joint pain, comprising a step of containing an effective amount of a water extract of button cucumber (Peucedanum japonicum Thumb. Var. Japonicum) .