JP6710408B2 - Composition containing black ginger extract - Google Patents

Description

The present invention relates to a composition containing a black ginger extract used for various purposes.

Osteoarthritis is caused by aging, mechanical stress, etc., resulting in the destruction of the surface of articular cartilage, the accompanying proliferation of new cartilage around the joint margin, joint deformity, and the delayed degeneration of joint cartilage. When it occurs, it is an arthritic disease often associated with pain and loss of function.

For arthritis such as osteoarthritis, analgesics and anti-inflammatory agents containing acetylsalicylic acid, indomethacin, diclofenac and the like as active ingredients, and rheumatoid arthritis therapeutic agents containing etanercept and the like as active ingredients are used.

Certainly, improvement of arthritis can be expected by using the above-mentioned drugs. However, although these drugs are effective against severe arthritis, they have side effects and cannot be used daily. In addition, a drug with few side effects that can be used for the purpose of preventing severe arthritis or for alleviating daily discomfort in joints is useful.

Therefore, the present invention aims to provide an active ingredient-containing composition that can be used daily and is highly safe and useful for arthritis such as osteoarthritis. And

The present inventors accumulated extensive research on the above problems, and examined the effects of various substances on the pain associated with osteoarthritis and the histological degeneration of articular cartilage, and surprisingly, the black ginger extract Found that it has a palliative effect on the pain and histological degeneration of articular cartilage. Since such a black ginger extract is derived from a natural product, black ginger, it is highly safe and can be used on a daily basis.

Even more surprisingly, the black ginger extract is comparable or even more markedly painful than ibuprofen and diclofenac, anti-inflammatory analgesics known to relieve arthritis and analgesic sites of inflammation. It was found that it has a palliative action and a joint and cartilage protective action. As a result, the present inventors have succeeded in creating a black ginger extract-containing product that can alleviate pain and maintain healthy joints and cartilage based on the above findings. The present invention is a completed invention based on this successful example.

Therefore, according to the present invention, there is provided an anti-arthritic composition containing a black ginger ( Kaempferia parviflora ) extract.

According to another aspect of the present invention, there is provided a joint protection composition or a cartilage protection composition containing a black ginger extract.

According to another aspect of the present invention, there is provided a composition for maintaining a gait function, which contains a black ginger extract as an active ingredient.

Preferably, the composition of the present invention is a composition used for persons with joint abnormality or middle-aged and elderly persons.

Preferably, the composition of the present invention is a composition containing the black ginger extract as a daily use unit of 50 to 5,000 mg/kg.

Preferably, the composition of the present invention is a composition containing 50 to 5,000 mg/kg of the black ginger extract as a daily use unit and used at a rate of once or more per week.

According to another aspect of the present invention, there is provided a locomocare agent containing a black ginger extract as an active ingredient.

According to another aspect of the present invention, there is provided a locomotive symptom relieving agent or a motor function maintaining agent comprising a black ginger extract as an active ingredient.

According to another aspect of the present invention, there is provided a relieving agent for sensation of discomfort during joint exercise, which comprises a black ginger extract as an active ingredient.

According to another aspect of the present invention, the use of a black ginger extract or a composition containing a black ginger extract alleviates, ameliorates pain associated with arthritis or arthritis or histological degeneration of articular cartilage, or Methods of control (but not medical treatment for humans) are provided.

According to another aspect of the present invention, there is provided a method for protecting joints or cartilage, which comprises using a black ginger extract or a composition containing the black ginger extract (excluding medical treatment for humans). To be done.

Preferably, in the present invention, the black ginger extract is a powdery black ginger extract obtained by freeze-drying a product obtained by extracting a pulverized black ginger product with 60% (V/V) ethanol. ..

According to the present invention, it is used on a daily basis, and is highly safe, to relieve pain associated with arthritis and to maintain healthy joints and cartilage, and to alleviate, improve, suppress, prevent and prevent arthritis. Can be expected to be treated.

It is the figure which showed the measurement result of the pain threshold value described in the Example. It is the figure which showed the evaluation result of Mankin Score described in Example 2 of an Example. It is a photograph figure which dye|stained the paraffin fixed section of the knee joint tissue of each group described in Example 3 of an Example.

Hereinafter, details of the present invention will be described.
The present invention is characterized by containing a black ginger extract as an active ingredient. The use composition and use agent containing the black ginger extract of the present invention are collectively referred to as "black ginger extract containing substance".

Black ginger ( Kaempferia parviflora ) is a plant belonging to the genus Angustiaceae, which is known to grow naturally in Southeast Asia. Black ginger is known to have the effects of enhancing energy, nourishing tonicity, lowering blood sugar level, recovering physical strength, improving digestive system, vaginal discharge, hemorrhoids, hemorrhoids, nausea, stomatitis, arthralgia, and gastric pain. Has been. Black ginger is a natural plant that has a long history of use in humans and has a high level of safety. Therefore, it can be applied to various uses.

The part of black ginger to be used is not particularly limited as long as it contains a component that contributes to a desired pharmacological action, and examples thereof include roots, leaves, stems, flowers, branches, and the like. It is a rhizome containing a large amount of polymethoxyflavonoid (PMF) such as dimethoxyflavone (57DMF).

The black ginger extract is not particularly limited as long as the components in black ginger are extracted, for example, an extract obtained by extracting black ginger or a processed product thereof with a solvent, a diluent or a concentrate thereof, or Examples thereof include dried products and powders thereof.

The black ginger extract is obtained by extracting black ginger or a processed product thereof with a solvent. Examples of the solvent used for extraction include lower alcohols such as ethanol, methanol, isopropanol, butanol; lower esters such as ethyl acetate and methyl acetate; acetone; mixed solvents of these with water. Water is also mentioned as an extraction solvent, and may be hot water or warm water. The black ginger extract is preferably extracted with water alone, ethanol alone, or a mixed solvent of water and ethanol (so-called hydrous ethanol). In particular, the black ginger extract obtained by using hydrous ethanol having a concentration of 40 to 70 vol% as a solvent is preferable.

When a mixed solvent is used as the solvent, for example, an acetone/water (2/8 to 8/2, volume ratio) mixture, an ethanol/water (2/8 to 8/2, volume ratio) mixture, etc. may be used. it can. In the case of ethanol/water, it is preferable to add a solvent in an amount of 2 to 20 times its mass to the rhizome of the black ginger and to perform extraction at room temperature or under heating for about 10 minutes to 48 hours.

The extraction method is not particularly limited, but for example, from the viewpoint of safety, convenience and industrialization, it is preferable to perform the extraction operation under conditions as gentle as possible. For example, a part of black ginger or a dried product thereof is crushed, crushed, shredded, etc., and a solvent in an amount of 2 to 20 times by mass is added to this, and 10 minutes to 48 hours in a range of 0°C to the reflux temperature of the solvent, Extraction is performed under any conditions such as standing, shaking, stirring, and refluxing. After the extraction work, solid-liquid separation operations such as filtration and centrifugation are performed to remove insoluble solid matter. An extract is obtained by performing operations such as dilution and concentration on this, if necessary. Further, the insoluble matter may be extracted by repeating the same operation, and the extract may be used together with the previous extract. These extracts may be further purified and used by a purification method usually used by those skilled in the art.

The dried powder of black ginger is, for example, a sliced black ginger after washing is dried in the sun or using a drier, and as it is, or a processed product obtained by cutting it into an appropriate shape and size, a crushing device. It can be obtained by pulverizing with. As the crushing device, those usually used can be widely used, but for example, a crusher including a raw material hopper, a crusher, a classifier, a product holder and the like can be used.

The obtained extract can be used as it is or after being concentrated, for example, in the form of a liquid, a concentrate, or a dried product obtained by drying these. The drying means is not particularly limited, and for example, spray drying, freeze drying, reduced pressure drying, fluidized drying and the like, which are commonly used by those skilled in the art, are used. Furthermore, the dried product obtained by the above method can be powdered and used by a method known to those skilled in the art.

From the viewpoint of storability and processability, the black ginger extract is preferably in powder form, and more preferably in dry powder form. The drying means is not particularly limited, and examples thereof include a drying means that heats, sun-drys, hot-air drying, and depressurizes the black ginger extract containing the solvent. The degree of drying may be such that it is confirmed that the solvent content of the black ginger extract is sufficiently reduced, and for example, until the solvent content becomes 10 wt% or less, preferably 5 wt% or less. It is a degree.

Examples of the pulverization method for obtaining the dry powder of the black ginger extract include a method of pulverizing and pulverizing the black ginger extract with a ball mill, a hammer mill, a roller mill or the like which is a method usually used by those skilled in the art. However, the present invention is not limited to these. It is also possible to reverse the order of drying and pulverization, pulverize the black ginger extract before drying in advance, and dry the pulverized product to obtain a black ginger extract dry powder.

The black ginger extract may be commercially available, and examples of the commercially available black ginger extract include "black ginger" (Toyo Shinyaku Co., Ltd.) and the like.

The black ginger extract has the effect of alleviating the pain caused by monoiodoacetic acid-induced osteoarthritis and the histological degeneration of articular cartilage, as shown in Examples described later. The effect, joint protection effect, cartilage protection effect, walking function maintenance effect, etc. can be expected. Black ginger extract not only improves already existing arthritis, pain and histological degeneration of articular cartilage, but also at the site where arthritis, pain and histological degeneration of articular cartilage may occur. By acting against them, it is probable to obviate these symptoms. In addition, black ginger extract, through its effect of improving osteoarthritis, is associated with diseases related to locomotor organs (locomo), such as kyphosis, easy fracture, degenerative spondylosis, and spinal canal stenosis associated with osteoarthritis. The effect of alleviating the dysfunctional locomotive syndrome (locomotive syndrome) and the effect of maintaining motor function can be expected. Naturally, the black ginger extract has a locomotive care effect and an effect of relieving discomfort during joint exercise. Therefore, the present invention, by using a black ginger extract as an active ingredient, an anti-arthritic composition, a joint protecting composition, a cartilage protecting composition, a walking function maintaining composition, a locomotive care agent, a locomotive symptom relieving agent. , Motor function maintenance agent, relieve of discomfort during movement of joint site, cartilage histological degeneration inhibitor, cartilage degeneration inhibitor, cartilage deformation inhibitor, cartilage damage inhibitor, knee cartilage histological degeneration inhibitor, knee cartilage It may take the form of a degeneration preventing agent, a knee cartilage deforming preventing agent, and a knee cartilage damage preventing agent.

The compounding amount of the black ginger extract in the black ginger extract-containing material of the present invention is not particularly limited as long as it is an effective amount that can exert at least a pain relieving effect or a joint or cartilage protecting effect. Further, as long as it contains at least an effective amount that can exert a pain relieving action or a joint or cartilage protecting action, it may consist of the black ginger extract alone.

The blending amount of the black ginger extract should be set so that the lower limit of the amount used per day is a dry mass of the black ginger extract, for example, 50 mg or more, preferably 100 mg or more, more preferably 200 mg or more. You can Further, the upper limit of the amount used per day can be set so as to be, for example, 5,000 mg or less, preferably 3,000 mg or less, and more preferably 2,000 mg or less in terms of the dry mass of the black ginger extract. ..

Specifically, the blending amount of the black ginger extract is 100 to 3,000 mg, and preferably 200 to 2,000 mg, in terms of the dry mass of the black ginger extract as the amount used per day. However, when the black ginger extract-containing substance of the present invention contains another substance having a pain relieving action or a joint or cartilage protecting action, the amount of the black ginger extract can be adjusted accordingly, for example.

The black ginger extract-containing product of the present invention may contain other components appropriately selected in addition to the black ginger extract. Other components include, for example, various excipients, binders, lubricants, stabilizers, diluents, extenders, thickeners, emulsifiers, colorants, fragrances, additives, cosmetic raw materials, pharmaceutical raw materials, etc. Can be mentioned. The content of other components can be appropriately selected according to the usage form of the black ginger extract-containing product of the present invention.

The black ginger extract-containing product of the present invention can be used in various forms for the purpose of obtaining a relieving effect on arthritis such as osteoarthritis and pain associated therewith or a protective effect on joints and cartilage. Oral or parenteral form. The black ginger extract-containing product of the present invention may be used orally or parenterally as it is, depending on its form, or may be dissolved in a solvent for dissolving the black ginger extract orally or It may be used parenterally.

The form of the black ginger extract-containing composition or the black ginger extract-containing agent of the present invention is not particularly limited and may be any form. As the form of the oral ginger extract-containing composition or the black ginger extract-containing agent, for example, a form suitable for oral use, specifically, granules, powder, tablets, chewable, Examples include capsules, liquids, and syrups.

The black ginger extract-containing composition or the black ginger extract-containing agent of the present invention is an oral composition for the purpose of improving arthritis, an oral composition for the purpose of protecting or maintaining the joint, or for the purpose of locomotive syndrome countermeasures. It can be used as an oral composition or the like.

As a form of the parenteral black ginger extract-containing, for example, a form suitable for parenteral use, specifically, lotion, cream, liquid, foundation, mist, emulsion, Examples include spray, mousse, and gel.

The packaging form of the black ginger extract-containing product of the present invention is not particularly limited and can be appropriately selected according to the dosage form, for example, blister pack such as PTP; strip packaging; heat sealing; aluminum pouch; plastic or synthetic resin. And the like; a glass container such as a vial; a plastic container such as an ampoule.

The black ginger extract-containing product of the present invention is preferably applied to humans, but is not particularly limited as long as the expected action and effect are exhibited, and it is applicable to animals other than humans. You can The user of the black ginger extract-containing product of the present invention is not particularly limited, and may be, for example, a healthy person, but a person who is expected to have a relieving effect on arthritis or pain or a joint or cartilage protecting effect. Is more preferable, and it is more preferable to use it for persons having joint abnormalities such as arthritis, and for middle-aged and older persons aged 40 or older. People with joint abnormalities and middle-aged and elderly people may have joint abnormalities and pain in the past, as well as those who may have joint abnormalities and pain due to heredity, occupation, etc. Included. The frequency of use of the black ginger extract-containing product of the present invention is not particularly limited and is, for example, once or more per week, preferably twice or more per week.

The compounding amount of the black ginger extract in the black ginger extract-containing product of the present invention can be appropriately set depending on the administration form, dosage form, etc. and is not particularly limited. For example, the total amount of black ginger extract is 100 parts by mass, the lower limit of the black ginger extract is 0.001 part by mass or more, 0.01 part by mass or more, preferably 0.1 part by mass. The amount of the black ginger extract can be set to 100 parts by mass or less, preferably 50 parts by mass or less, and more preferably 10 parts by mass or less.

The content of the black ginger extract in the black ginger extract-containing material of the present invention is, for example, 100 parts by mass as a whole, and the ratio of 57DMF content is 0.3 part by mass or more, preferably 0.5 part by mass as a lower limit. It is preferably not less than 30 parts by mass, more preferably not more than 20 parts by mass, and even more preferably not more than 10 parts by mass.

The black ginger extract-containing product of the present invention can contain, in addition to the black ginger extract, a second physiologically active component having an action of relieving arthritis or pain or an action of protecting joints and cartilage. Such a second physiologically active component is not particularly limited as long as it is a physiologically active component which has an action of relieving arthritis and pain or a action of protecting joints and cartilage, which are generally known. For example, an analgesic, Examples thereof include anti-inflammatory agents and therapeutic agents for arthropathy. By containing the black ginger extract and the second physiologically active ingredient, the black ginger extract-containing composition of the present invention has a synergistic effect of alleviating arthritis and pain or a function of protecting joints and cartilage. Can be a thing. The second bioactive ingredient can be one or more ingredients. The amount of the second physiologically active ingredient used is not particularly limited as long as it does not prevent the solution of the problems of the present invention, and is appropriately adjusted.

The method for producing the black ginger extract-containing product of the present invention is not particularly limited, and may be produced according to a general production method known to those skilled in the art depending on the use form. For example, for granules or solids, the black ginger extract as it is or a mixture of the above-mentioned other ingredients and the second physiologically active ingredient at the same time or in several stages is mixed by a fluid bed granulation method, Granules can be formed into granules according to a granulation method such as a stirring granulation method and an extrusion granulation method, and further compression-molded according to a conventional method using a tableting machine or the like to form tablets.

Another aspect of the present invention comprises using a black ginger extract or a composition containing the black ginger extract to alleviate, improve or suppress arthritis or pain associated with arthritis, histological degeneration of articular cartilage and the like. Is the way to do it. Yet another aspect of the invention is a method of protecting joints or cartilage comprising using a black ginger extract or a composition containing a black ginger extract. However, the method of the present invention excludes medical treatment for humans.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples, and the present invention can take various aspects as long as the problems of the present invention can be solved. ..

[Example 1. Effect of black ginger extract on joint pain]
It was demonstrated as follows that the black ginger extract has a particularly remarkable joint pain relieving effect on monoiodoacetic acid-induced arthritis model rats.

(1) Experimental animal A 6-week-old male wistar rat was acclimated for 5 days or more. As a rearing environment, the lighting time was 12 hours, and the cage was a polycarbonate flat-bottom cage (W260 x D420 x H180 mm; CLEA Japan, Inc.) with wood chips (soft chips; Japan SLC, Inc.) as the floor. The number of individuals housed in was 2 to 3.

1, 3, and 6 days before the start of the test, training for measuring the pain threshold (right foot) was performed on the plantar surface using a Von Frey type pain sensation measuring device (DYNAMIC PLANTAR AESTHESIOMETER: 37450), and pre-drug data was obtained. In addition, the weight value was measured on the day before the test. 12 groups per group were divided into 3 groups so that the pain threshold value (right foot) and body weight value on the day before the test were almost uniform, and they were subjected to the test (priority order; pain threshold value> body weight value).

(2) Monoiodoacetate-induced arthritis model rat from the start date (Day 0) of the establishment test, under anesthesia with diethyl ether, monoiodoacetate (MIA; Sigma-Aldrich Japan) was administered at 3 mg/50 μL/rat to the lumen of the right knee joint. By administration, monoiodoacetic acid-induced arthritis model rats were established.

(3) Test substance Black ginger extract (BG; black powder) and ibuprofen (Wako Pure Chemical Industries, Ltd.; white powder) were used as test substances, and sodium carboxymethylcellulose (Wako Pure Chemical Industries, Ltd.; CMC) was used as a control substance. White powder) was used. The black ginger extract was prepared by the following method.

After cleaning the rhizome of the black ginger, it was sliced to about 1 to 10 mm and sun-dried for one day. Then, it dried with the oven dryer set to 40-100 degreeC for 4 to 6 hours, coarsely pulverized, and sterilized at 130 to 200 degreeC for 5 to 20 seconds. The sterilized coarse crushed product was crushed by a crusher to obtain a crushed black ginger rhizome. By the same method, a crushed black ginger stem, a crushed leaf and a crushed flower were obtained. These were crushed black ginger.

1000 g of crushed black ginger obtained by the above method was weighed and put in an Erlenmeyer flask together with 10 L of 60% (V/V) ethanol. The first extraction was carried out by allowing the mixture to stand at room temperature for 24 hours while stirring several times. This was filtered under reduced pressure to obtain the first extract. The residue after vacuum filtration was immersed in 3 L of 60% (V/V) ethanol and left standing at room temperature for 24 hours to perform a second extraction. This was filtered under reduced pressure to obtain a second extract. The extraction mixture solution obtained by combining the first and second extraction solutions was freeze-dried to obtain a powdery black ginger extract.

A test substance solution was prepared by dissolving or suspending the above substance in CMC in each of three groups of experimental animals so as to have a predetermined concentration shown in Table 1 below.

(4) Experimental method The test substance solution was forcibly orally administered to a monoiodoacetic acid-induced arthritis model rat. Specifically, the test substance solution was forcibly orally administered to a monoiodoacetic acid-induced arthritis model rat using a sonde at 10 mL/kg based on the weight value measured on the nearest day. The test substance was administered once a day for 21 days.

In principle, the feeding method was free intake. MF solid feed (Oriental Yeast Co., Ltd.) was used as the feed, and tap water was used as the drinking water.

During the test period, pain threshold measurement was performed using a Von Frey type pain sensation measuring device. That is, the pain threshold value of the sole of the right foot of each experimental animal was measured by the Von Frey type pain sensation measuring device. The measurement was carried out before MIA administration and on days 7, 14 and 21 after MIA administration. The pain threshold was determined by confirming withdrawal behavior for pain and flinching of the foot.

(5) Statistical processing With respect to the obtained measured values, the average value (mean), standard deviation (SD) and standard error (SE) of each group were calculated. The test was carried out by comparison between two groups (control unpaired t-test) between the control group or the control group and each group. The significance level was 5%.

(6) Experimental Results The measurement results of the pain threshold value for each week are shown in FIG. The smaller the pain threshold value, the easier it is to feel pain. Further, the bar and the symbol in the figure represent the fluctuation (g) of the pain threshold value and the significance level (5% or less), respectively. As shown in FIG. 1, when the black ginger extract (BG) was used, the pain was significantly suppressed from the second week on the control. Surprisingly, the black ginger extract showed a pain suppressing effect earlier than ibuprofen, which is known to have a pain suppressing effect. In addition, the pain-suppressing effect at the third week was not different between the black ginger extract and ibuprofen. From these results, it was found that the black ginger extract had a particularly remarkable joint pain relieving effect. Further, due to such joint pain relieving action, the black ginger extract may have an action of relieving, improving or suppressing fast-acting arthritis or pain associated with arthritis, and may further have a action of protecting joints and cartilage. It is suggested.

[Example 2. Effect of black ginger extract on the degree of articular cartilage degeneration]
It was demonstrated as follows that the black ginger extract has a particularly remarkable histologic degenerative effect of articular cartilage on monoiodoacetic acid-induced arthritis model rats.

(1) In the same manner as in Experimental Method Example 1, a test substance solution was orally administered to a monoiodoacetic acid-induced arthritis model rat. The test substance was administered once a day for 7 days. It should be noted that diclofenac (Wako company; white powder) was used instead of ibuprofen as a test substance, and the test substance was dissolved in CMC in each of the three groups of experimental animals so that the test substance had a predetermined concentration shown in Table 2 below. A test substance solution was prepared by suspending.

Seven days after the start of administration, dissection was performed, and the rat hind limb was sampled mainly in the knee joint tissue portion and fixed with 10% neutral buffered formalin solution. Next, the fixed knee joint tissue was decalcified and then embedded in paraffin to prepare a paraffin fixed section. The obtained paraffin-fixed section was stained with hematoxylin/eosin staining and safranin-O-fast green staining. The histological degeneration of articular cartilage of the stained sections was evaluated by the Mankin method and scored to obtain a Mankin Score. A paraffin-fixed section of knee joint tissue was prepared in the same manner using experimental animals, and this was used as a normal group.

(2) Experimental Results Mankin Score obtained by evaluating the degree of histological degeneration of articular cartilage is shown in FIG. A photograph of the stained section is shown in FIG. As shown in FIGS. 2 and 3, when the black ginger extract (BG) was used, the degree of histological degeneration of articular cartilage was alleviated. Also, surprisingly, the degree was greater than diclofenac, a known anti-arthritic agent. From these results, it was found that the black ginger extract had a particularly remarkable protective effect on joints and cartilage.

According to the present invention, a black ginger extract containing a joint pain relieving effect and a joint and cartilage protecting effect can be obtained, which is useful for those who have or may have arthritis, to protect or maintain the joint. Can be used as an oral composition for the purpose, an oral composition for the purpose of preventing locomotive syndrome, and the like. Further, in the case of a parenteral composition, it can be used as a quasi drug, a cosmetic, or a drug.

Claims (2)

A composition for alleviating osteoarthritis, which comprises a black ginger extract ( Kaempferia parviflora ). The composition according to claim 1, wherein the composition is a composition used for maintaining a walking function.