JP2019127458A - Arthritis improver - Google Patents

Abstract

To provide a novel arthritis improver.SOLUTION: An arthritis improver contains at least one selected from potassium salt and magnesium salt of proteoglycan as an active ingredient. The arthritis improver can be put into various forms of preparations and can be taken or ingested directly as pharmaceuticals and health foods, and can be also eaten or drunk by blending in various foods and drinks.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a novel joint inflammation improving agent.

  Joint inflammation represented by rheumatoid arthritis and osteoarthritis (bone arthropathy) is an inflammatory disease of the joints, and when it develops, it causes joint pain and swelling, etc., and it causes a deterioration in the quality of life (QOL). It is well known. Therefore, research and development of joint inflammation ameliorating agents have been energetically performed for a long time, and the research group of the present inventors is also not patenting that proteoglycans derived from salmon nasal cartilage can be used as active ingredients of joint inflammation ameliorating agents. It reports in the literature 1. However, the search for the active ingredient of the better joint inflammation improving agent is still in need.

Sayuri Yoshimura et al. , Attenuation of Collagen-Induced Arthritis in Mice by Salmon Proteoglycan, BioMed Research International Volume 2014 (2014), Article ID 406453

  Then, an object of the present invention is to provide a novel joint inflammation improving agent.

  As a result of intensive studies in view of the above points, the present inventors have found that potassium and magnesium salts of proteoglycan exert an excellent improving action on type II collagen-induced arthritis.

  The joint inflammation improving agent of the present invention made on the basis of the above findings contains at least one selected from potassium salt and magnesium salt of proteoglycan as an active ingredient as described in claim 1.

  ADVANTAGE OF THE INVENTION According to this invention, the novel joint inflammation improving agent which uses as an active ingredient at least 1 sort (s) selected from the potassium salt and magnesium salt of proteoglycan can be provided.

In Example 1, it is a graph which shows that the potassium salt and magnesium salt of proteoglycan exhibit the outstanding improvement effect with respect to type II collagen induction arthritis.

  The joint inflammation improving agent of the present invention comprises at least one selected from proteoglycan potassium and magnesium salts as an active ingredient. In the present invention, the term “improvement” is intended to include both prophylactic and therapeutic concepts.

  Proteoglycan is a glycoconjugate consisting of a core protein and glycosaminoglycan (acid mucopolysaccharide) that binds to it, and is present in the skin, cartilage, bone, and vascular wall as the main component of the extracellular matrix. Is a known substance. Proteoglycan can be obtained, for example, by purifying it using cartilage such as salmon, shark, cow, and whale as a raw material. As a typical obtaining method, acetic acid described in JP-A-2002-69097 is used. Can be mentioned. In this method, for example, crude proteoglycan is eluted from minced salmon nasal cartilage using acetic acid as an elution solvent, the resulting eluate is filtered and then centrifuged, and sodium chloride saturated ethanol is added to the supernatant. In this method, a semi-solid precipitate containing a crude proteoglycan obtained by centrifugation is dissolved in acetic acid and then dialyzed. According to this method, for example, a molecular weight of about 100 to 1500 kDa is obtained from salmon nasal cartilage. The proteoglycan from salmon nasal cartilage obtained in this way can be obtained commercially (Kakuhiro Proteoglycan Research Institute Co., Ltd.). The magnesium salt of proteoglycan as an active ingredient in the present invention can be prepared by converting such proteoglycan to a magnesium salt. The method of converting proteoglycan into a magnesium salt may be a method known per se, for example, a method of treating proteoglycan with a strongly acidic cation exchange resin of magnesium ion type. In addition, proteoglycan is converted to magnesium salt by treating proteoglycan with 1 M or less of hydrochloric acid or citric acid at low temperature, removing added acid and liberated low molecule, and then adding magnesium chloride or magnesium acetate. Alternatively, it can also be carried out by a method of adding high concentration sodium chloride or magnesium chloride to an aqueous solution of proteoglycan (Japanese Patent Laid-Open No. 2017-48150). In addition, the potassium salt of proteoglycan as an active ingredient in the present invention can be prepared by a method according to a method for converting proteoglycan to a magnesium salt.

  In the present invention, proteoglycan potassium salt or magnesium salt as an active ingredient can be taken or ingested as a pharmaceutical or health food by formulating it into various pharmaceutical forms, and also incorporated into various foods and drinks By eating and drinking, it exerts an excellent joint inflammation improving action. The amount to be applied varies depending on the age and weight of the user, the degree of symptoms, the form of application, etc., but is not particularly limited.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is limited to the following description and is not interpreted.

Example 1:
The effects of proteoglycan and its metal salt (sodium salt, potassium salt, magnesium salt) on type II collagen-induced arthritis were examined. The proteoglycan used was a commercial product derived from salmon nasal cartilage (Kadohiro Proteoglycan Laboratory), and its metal salt was prepared as follows according to the method described in JP-A-2017-48150.

(Magnesium salt of proteoglycan)
A glass column (inner diameter 4.6 cm, height 12 cm) is packed with a strongly acidic cation exchange resin (AG 50W-X8 resin, 100-200 mesh, manufactured by Bio-Rad), and Mg type using a 1M magnesium chloride solution. And then washed with deionized water until neutral. Next, a solution in which 1.2 g of proteoglycan was dissolved in deionized water was added from above the column at room temperature and flowed down. Thereafter, 400 mL of deionized water was flowed down to the resin at a flow rate of 2 mL / min, and the obtained eluate was concentrated with an evaporator (Tokyo Science Instruments Co., Ltd.) and then freeze-dried to obtain a white flocculent solid ( Yield: 1.2 g).
(Sodium salt of proteoglycan)
A white fluffy solid, in the same manner as the preparation of the magnesium salt of proteoglycan except that the strongly acidic cation exchange resin is converted to the Na form using 2 M sodium hydroxide solution instead of 1 M magnesium chloride solution. (Yield: 1.1 g).
(Potassium salt of proteoglycan)
A white flocculent solid is obtained in the same manner as the method for preparing the magnesium salt of proteoglycan except that a strongly acidic cation exchange resin is made K-type using a 2M potassium hydroxide solution instead of a 1M magnesium chloride solution. (Yield: 1.1 g).

(experimental method)
Seven-week-old female DBA / J mice were divided into the following six groups, and individual mice developed type II collagen-induced arthritis (one group, five mice).
-Proteoglycan non-administration group-Proteoglycan administration group-Proteoglycan sodium salt administration group-Proteoglycan potassium salt administration group-Proteoglycan magnesium salt administration group Type II collagen (50 µg) and Freund's complete adjuvant The mixture was mixed at a ratio of 1: 1 and administered subcutaneously to the tail of the mouse. The test substance is mixed with the feed so that each mouse ingests 1 mg of the test substance per day after checking the average daily intake (fat component 5.6% normal diet) average intake of each mouse. Administered. Administration of the test substance started from the day when type II collagen was administered and continued until the end of the experiment. Arthritis was evaluated by scoring once every three days from day 21 to day 57 on which type II collagen was administered. Scores are given by Edward F. Rosloniec et al. , Collagen- Induced Arthritis, Current Protocols in Immunology, April 2010, as follows.
0 No redness or swelling in the ankle and tarsal bone 1 Mild redness and swelling limited to the ankle and tarsal bone 2 Mild redness and swelling from the ankle to tarsal bone 3 Moderate from the ankle to tarsal bone Redness and swelling 4 Severe redness and swelling from ankle to tarsal bone

(Experimental result)
As shown in FIG. As is clear from FIG. 1, the improvement effect of the metal salt of proteoglycan on type II collagen-induced arthritis varies depending on the type of metal salt, and potassium salt and magnesium salt exhibited an improvement effect superior to that of proteoglycan. Did not demonstrate.

Formulation Example 1: Tablet A tablet exhibiting the joint inflammation improving action comprising the following component composition was produced by a method known per se.
Potassium salt of proteoglycan 1
Lactose 80
Magnesium stearate 19 (unit: wt%)

Formulation Example 2: Biscuit A biscuit having an arthritis ameliorating effect comprising the following component composition was produced by a method known per se.
Magnesium salt of proteoglycan 1
Weak flour 32
Whole egg 16
Butter 16
Sugar 24
Water 10
Baking powder 1 (Unit:% by weight)

  The present invention has industrial applicability in that a novel joint inflammation improving agent can be provided.

Claims (1)

  A joint inflammation ameliorating agent comprising as an active ingredient at least one selected from potassium and magnesium salts of proteoglycan.