JP2004026846A - Therapeutic or prophylactic composition for arthralgia - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a medicinal composition useful for improving arthropathy such as arthralgia. <P>SOLUTION: This composition for improving arthropathy such as arthralgia is obtained by mixing 1 pt. wt. vitamin B1 with 1-1,000 pts. wt. glycosamine, or the like (glycosamine, its salts, or the like) and the composition may contain 10-300 pts. wt. glycosaminoglycan, or the like, (chondroitin, chondroitinsulfuric acid, its salts, or the like) per 100 pts. wt. total of vitamin B1 and glycosamine, and vitamin B6 and/or vitamin B12 may be contained therein. <P>COPYRIGHT: (C)2004,JPO

Description

The present invention relates to a composition for preventing or treating joint disorders containing vitamins B1, glucosamines and, if necessary, glycosaminoglycans.

Joints are easily irritated easily because they are always mechanically stimulated by exercise. Causes of inflammation are various, such as joint deformation, bacterial / viral infection, trauma, immune diseases such as allergies, and metabolic abnormalities due to nephritis and the like.

Vitamin B1 is used for Wernicke's encephalopathy, peripheral neuropathy, central nervous disorder, neuralgia, muscle pain, joint pain (low back pain, stiff shoulders, fifty shoulders), numbness of limbs, eye strain, constipation, nutritional supplementation, etc. I have. The effect of vitamins B1 on joint pain is particularly effective for relatively mild joint pain symptoms such as lazy knee joints.

With respect to a solid preparation containing vitamin B1, Japanese Patent Application Laid-Open No. Hei 5-27072 (Patent Document 1) discloses that a succinic acid ester of tocopherol or a salt thereof and a vitamin B1 or ascorbic acid, and at least one of the components is coated. Disclosed are vitamin preparations coated with an agent. JP-A-2000-247879 (Patent Document 2) discloses a vitamin preparation containing a succinic acid ester of tocopherol or a salt thereof, vitamins B1 and a specific basic inorganic compound. JP-A-9-268127 (Patent Document 3) discloses a solid preparation containing a vitamin B1 derivative, starch, and calcium hydrogen phosphate. Further, regarding a liquid preparation containing vitamin B1, JP-A-5-255069 (Patent Document 4) discloses that a vitamin group containing at least one of 13 essential vitamins includes at least one selected from leucine, isoleucine, methionine, and valine. An intravenous vitamin formulation containing one is disclosed.

On the other hand, chondroitin is a biological macromolecule that is particularly distributed abundantly in cartilage tissue, and protects the corneal surface, sensorineural hearing loss (acoustic trauma), chronic nephritis, neuralgia, arthralgia, lumbago, shoulder periarthritis ( It is used to prevent adhesions after laparotomy. Numerous pharmaceuticals containing sodium chondroitin sulfate have also been marketed or proposed. For example, Japanese Patent Publication No. 9-503197 (Patent Document 5) discloses a composition for treating connective tissues of humans and animals, which contains glycosaminoglycans such as chondroitin and amino sugars such as glucosamine. ing. This composition has been utilized to prevent and treat joint pain with recovery of connective tissue. JP-A-2000-53569 (Patent Document 6) discloses L-carnitines, glucosaminoglycans (such as chondroitin sulfate), glucosamine, and excipients as compositions suitable for the prevention and treatment of joint disorders. Compositions containing are disclosed.

Further, there is a need for a composition that is more effective for the prevention and treatment of joint disorders such as joint pain.
JP-A-5-27072 JP 2000-247879 A JP-A-9-268127 JP-A-5-255069 Japanese Patent Publication No. 9-503197 JP-A-2000-53569

An object of the present invention is to provide a pharmaceutical composition useful for preventing or treating joint disorders such as joint pain.

Another object of the present invention is to provide a pharmaceutical composition that can effectively improve joint disorders such as joint pain and is useful for extending the range of motion (or range of motion) of a joint.

The present inventors have conducted intensive studies to achieve the above object, and as a result, it has been found that a joint of vitamin B1 and glucosamine, particularly a combination of glycosaminoglycans such as chondroitin sulfate can significantly reduce joint pain, The present inventors have found that the present invention is effective for the prevention or treatment of, and completed the present invention.

That is, the composition for preventing or treating arthralgia according to the present invention is a composition containing vitamin B1 and glucosamine, wherein the glucosamine is added in an amount of 1 to 1000 parts by weight based on 1 part by weight of vitamin B1. Include in percentage. The composition for treating or preventing joint pain of the present invention contains vitamin B1 and glucosamine, and the content of vitamin B1 is 0.001 to 30% by weight based on the whole. These compositions may further include glycosaminoglycans. Glucosamine or a salt thereof can be used as the glucosamine, and chondroitin, chondroitin sulfate or a salt thereof can be used as the glycosaminoglycan. The proportion of glycosaminoglycans may be about 10 to 300 parts by weight based on 100 parts by weight of the total amount of the vitamin B1 and glucosamine. The pharmaceutical composition of the present invention may further contain vitamin B6 and / or vitamin B12.

As used herein, the term "composition for treating or preventing joint pain" includes a composition for improving joint pain and a composition for preventing or treating joint disorders such as osteoarthritis or arthritis that cause joint pain. .

で は In the present invention, since vitamin B1s and glucosamines are combined, they are useful for preventing or treating joint pain. In addition, joint pain can be effectively improved, and the movable range or movable range of the joint can be expanded. It is more effective to further contain glycosaminoglycans.

ビ タ ミ ン Vitamin B1 contained in the composition of the present invention includes thiamine, thiamine derivatives and salts thereof, and the thiamine derivatives may be disulfide type, acyl type and the like. Examples of the thiamine derivative include bisthiamine, thiamine disulfide (TDS), thiamine dicetyl sulfate, benfotiamine (BTMP), prosultiamine (TPD), fursultiamine (TTFD), bisbenthamine (BTDS), Sicotiamine (CCT), octiamine (TATD), alitiamine, thiamine propyl disulfide, thiamine tetrahydrofurfuryl disulfide (TPFD), dicetiamine (DCET), bisbutiamine, bisibutiamine (DBT), thiamine monophosphate disulfide, thiamine pyrophosphate, sicotiamine , Thiamine ethyl disulfide, thiamine propyl disulfide and the like. Examples of the thiamine salts include physiologically acceptable salts, for example, hydrochlorides such as thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, disetiamine hydrochloride, and fursultiamine hydrochloride, and nitrates. These vitamins B1 can be used alone or in combination of two or more.

の う ち Among these vitamins B1, thiamine, thiamine disulfide, benfotiamine, fursultiamine, bisbenthamine, dicetiamine, thiamine ethyl disulfide, and thiamine propyl disulfide are preferable from the viewpoint of stability. In particular, bisbenthamine, fursultiamine and thiamine are preferred from the viewpoint of stability and absorbability.

The amount of the vitamin B1 is, for example, about 0.001 to 30% by weight, preferably about 0.01 to 20% by weight, and more preferably about 0.1 to 10% by weight, based on the whole preparation (particularly, a solid preparation). It can be selected from a range, and is usually about 0.1 to 5% by weight. In the liquid preparation, the content of the vitamin B1 is usually preferably about 0.0002 to 0.03 w / v% based on the whole.

Note that vitamins B1 may be used in combination with other vitamins. Other vitamins include, for example, water-soluble vitamins [vitamin B2 (riboflavins such as sodium flavin adenine dinucleotide, riboflavin, sodium riboflavin phosphate, riboflavin butyrate), and vitamin B6 (vitamin B6, pyridoxine, pyridoxal, etc.). Pyridoxine, physiologically acceptable salts (hydrochlorides such as pyridoxine hydrochloride, corresponding acetates, phosphates such as pyridoxal phosphate, etc.)), vitamin B12 (vitamin B12, mecobalamin, cyanocobalamin, hydroxocobalamin, Vitamin Bs and Cs (ascorbic acid, calcium ascorbate) such as cobalamins such as methylcobalamin or their physiologically acceptable salts (eg, hydrochloride, acetate such as hydroxocobalamin acetate); , Sodium ascorbate, etc.), nicotinic acids (nicotinic acid, nicotinic acid amide, etc.), pantothenic acids (panthenol, pantothenic acid or a salt thereof, etc.), biotin, folic acid, etc., fat-soluble vitamins [vitamin A (retinol acetate, etc.) , Retinol palmitate, vitamin A oil), vitamin Ds (ergocalciferol, cholecalciferol, etc.), vitamin Es (liver oil, strong liver oil, d-α-tocopherol acetate, dl-α-tocopherol acetate, d- α-tocopherol, dl-α-tocopherol, etc.), vitamin K, etc.]. These vitamins can also be used alone or in combination of two or more. Vitamin B1 is usually useful in combination with water-soluble vitamins (such as vitamin B), for example, vitamin B6 and / or vitamin B12. In addition, pyridoxine is preferable among the vitamin B6, and cyanocobalamin or hydroxocobalamin is preferable among the vitamin B12. In addition, it is preferable to use in combination with vitamin Cs, vitamin B6 and / or vitamin B12 in order to improve or reduce joint pain in a comprehensive and advantageous manner.

The ratio (weight ratio) between vitamin B1 and other vitamins is the former / the latter = 100/0 to 20/80, preferably 100/0 to 30/70, and more preferably about 100/0 to 50/50. May be selected from the range.

In the present invention, by combining vitamin B1 and glucosamines, joint pain can be effectively alleviated or improved, and is useful as a composition for preventing and treating joint pain. In addition, since vitamin B1 can be effectively stabilized by blending glucosamines, the physiological activity or pharmacological activity of vitamin B1 can be effectively used.

Examples of glucosamines include glucosamine, glucosamine salts (physiologically acceptable salts such as hydrochloride and sulfate, for example, inorganic acid salts such as glucosamine hydrochloride, glucosamine sulfate and glucosamine phosphate), and glucosamine derivatives (N-acetylglucosamine, N-methyl-L-glucosamine, etc.). Glucosamines may be in D, L or DL form. These glucosamines can be used alone or in combination of two or more. Preferred glucosamines are glucosamine or a salt thereof (such as glucosamine hydrochloride).

Note that glucosamine or a salt thereof, which is a typical amino sugar, can be obtained by purifying shrimp, crab, squid, or the like by enzymatic or hydrolysis treatment, and a commercially available product can also be used.

The amount of glucosamines such as glucosamine can be selected from a wide range of about 1 to 99.9% by weight based on the whole solid preparation, and is usually 5 to 99.9% by weight (for example, 7.5 to 99.9%). %), Preferably about 10 to 90% by weight, and more preferably about 10 to 80% by weight. The amount of glucosamine is usually about 10 to 60% by weight. The content of glucosamines in the solution is, for example, about 0.001 to 10 w / v%, preferably about 0.01 to 10 w / v%, and more preferably about 0.01 to 5 w / v%.

The ratio of glucosamines to vitamin B1 may be an effective amount capable of improving joint pain, for example, 0.1 to 1000 parts by weight, preferably 1 to 500 parts by weight of glucosamine per 1 part by weight of vitamin B1. And more preferably about 1 to 300 parts by weight. The amount of glucosamine used is usually 1 to 100 parts by weight, particularly about 2 to 50 parts by weight, per 1 part by weight of vitamin B1.

に お い て In the present invention, the use of glycosaminoglycans (mucopolysaccharide or acidic mucopolysaccharide) can further improve the physiological activity or pharmacological activity against joint disorders. In the case of solid preparations, glucosamines can significantly suppress the formation of gels due to glycosaminoglycans, and can improve disintegration. Therefore, when the present invention is applied to a solid preparation containing glycosaminoglycans, the activity of vitamin B1 and glucosamine can be effectively expressed. In addition, disintegration in the digestive tract is promoted without being affected by fluctuations in pH, and the active ingredient can be stably released. For example, the disintegration of the solid preparation can be greatly improved even if the pH fluctuates in a range of about 1 to 10 (for example, about 1 to 7), particularly in a low pH range (for example, about 1 to 4). Therefore, even if the intragastric pH fluctuates in the range of 1.2 to 6.8, the effect of improving joint pain can be kept high.

Glycosaminoglycans are a series of acidic polysaccharides including glucosamines, and include, for example, hyaluronic acid, chondroitin, jaruronic acid, heparan, keratan or salts thereof. Examples of the salts of glycosaminoglycans include alkali metal salts (eg, sodium salts such as sodium hyaluronate), sulfated glucosaminoglycans (chondroitin sulfate A (chondroitin 4-sulfate), chondroitin sulfate B (dermatan sulfate), chondroitin Examples thereof include chondroitin sulfate such as sulfate C (chondroitin 6-sulfate), heparin, heparan sulfate, keratan sulfate I, and keratan sulfate II. The sulfated glucosaminoglycan may be a metal salt such as sodium, potassium, calcium, magnesium, iron, manganese or the like, or a salt such as ammonium salt. These glycosaminoglycans can be used alone or in combination of two or more.

Preferred glycosaminoglycans include hyaluronic acid or a salt thereof (such as sodium hyaluronate), chondroitin or chondroitin sulfate or a salt thereof (such as a metal salt of chondroitin sulfate). Particularly, chondroitin or chondroitin sulfate or a salt thereof is preferable.

Chondroitin or a salt thereof can be obtained from animal cartilage or natural products such as collagen, and commercially available products can also be used. Not only purified chondroitin, but also chondroitin or a salt thereof can be used as an animal cartilage powder, extract or extract. The salts may be any physiologically acceptable salts such as hydrochloride and sulfate. Purified chondroitin or chondroitin sulfate or a salt thereof is more preferable in view of safety and absorbability.

The compounding amount of glycosaminoglycans such as chondroitin sulfate can be selected from a wide range of about 0.5 to 90% by weight based on the whole composition. For example, the compounding amount of glycosaminoglycans is 1 to 90% by weight. %, Preferably about 5 to 80% by weight, more preferably about 10 to 70% by weight, and usually about 10 to 60% by weight, preferably about 10 to 50% by weight.

The amount of glycosaminoglycans (such as chondroitin sulfate) can be selected from a wide range of about 1 to 500 parts by weight, for example, based on 100 parts by weight of the total of vitamin B1 and glucosamines. The amount of glucosamine used is 10 to 300 parts by weight (for example, 20 to 300 parts by weight), preferably 30 to 200 parts by weight, more preferably 50 to 100 parts by weight of the total amount of vitamin B1 and glucosamines. About 150 parts by weight.

If necessary, the pharmaceutical composition of the present invention may contain other physiologically active ingredients and pharmacologically active ingredients, for example, analgesics for joints and muscles (analgesic antipyretics such as acetaminophen, ibuprofen, salicylic acid derivatives, mefenamic acid, anti-inflammatory agents, antihistamines) ), Aminoethylsulfonic acid, γ-oryzanol, crude drug components (processed garlic, carrot, yoquinin, etc.), inorganic salts (equivalent mixture of potassium and magnesium aspartate, calcium glycerophosphate, calcium gluconate, calcium gluconate, precipitated calcium carbonate, calcium lactate, Anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, etc., caffeine (caffeine, anhydrous caffeine, etc.), amino acid or a salt thereof (L-cysteine, L-cysteine hydrochloride, etc.), glucuronolactone, glucuronic acid, mineral Contains It may be.

Further, the dosage form of the preparation of the present invention is not particularly limited, and may be a liquid preparation (suspension, emulsion, syrup, injection, etc.) or a solid preparation (powder, fine granule, granule, pill, capsule) , Tablets, etc.).

製 剤 The preparation of the present invention can be prepared by a conventional method by adding a conventional carrier component according to the form of the preparation as long as stability and the like are not impaired. In the solid preparation, as the carrier component or additive, for example, excipients (sugar alcohols such as D-sorbitol, D-mannitol, xylitol, sugars such as glucose, sucrose, lactose, fructose, crystalline cellulose, carmellose sodium, Disintegrator (low substitution degree) calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light silicic anhydride, titanium oxide, magnesium aluminate metasilicate, talc, kaolin, etc. Hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, partially pregelatinized starch, etc .; binders (methylcellulose, ethylcellulose, hydroxypropylcell) Cellulose, cellulose derivatives such as hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol alginate, etc.); Agents (stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, beeswax, etc.); antioxidants (dibutylhydroxytoluene (BHT), Propyl gallate, butylhydroxyanisole (BHA), tocopherol, citric acid, etc.); coating agent (hydroxypropylmethylcellulose, Hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinylacetal diethylaminoacetate, aminoalkyl methacrylate copolymer, hydroxypropylmethylcellulose acetate succinate, methacrylic acid Coloring agents (turmeric extract, riboflavin, titanium oxide, carotene solution, etc.); Flavoring agents (aspartame, ascorbic acid, stevia, menthol, licorice crude extract, single syrup, etc.); Surfactant (polyoxyethylene cured castor Glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, macrogol, sucrose fatty acid ester, etc.); plasticizers (triethyl citrate, polyethylene glycol, Sweeteners (natural or synthetic sweeteners such as sucrose, mannitol, aspartame); flavorants (such as menthol); adsorbents, preservatives, wetting agents, and antistatic agents.

In liquid solutions, water or alcohol-containing water can be usually used as a carrier component, and can be formulated using conventional components. Examples of the additional component of the liquid agent include a pH adjuster (citric acid, malic acid, sodium hydrogen phosphate, dipotassium phosphate, etc.), a cooling agent (l-menthol, peppermint water, etc.), the surfactant, and a surfactant. Turbidity agents (kaolin, carmellose sodium, xanthan gum, methylcellulose, tragacanth, etc.), defoamers (dimethylpolysiloxane, silicone defoamer, etc.), thickeners (xanthan gum, tragacanth, methylcellulose, dextrin, etc.), solubilizer (Ethanol, sucrose fatty acid ester, macrogol, etc.), the above-mentioned antioxidants, coloring agents, sweeteners, flavoring agents and the like.

組成 The composition (formulation composition) of the present invention can be obtained as it is or by appropriately applying a conventional method in the art. For example, a tablet can be prepared by mixing a powdery active ingredient and a pharmaceutically acceptable carrier ingredient (eg, excipient) and compression-molding the mixture. Further, among solid preparations, granules such as granules can be obtained by various granulation methods (extrusion granulation method, pulverization granulation method, dry compaction granulation method, fluidized bed granulation method, tumbling granulation method, high-speed granulation method). Tablets may be prepared by an appropriate combination of the above granulation methods and tableting methods (wet tableting method, direct tableting method) and the like. Furthermore, capsules can be prepared by filling powders and granules (powder, granules, etc.) in capsules (soft or hard capsules) by a conventional method. A preferred dosage form of the solid preparation is a tablet (for example, a chewable tablet in the mouth). Tablets may be sugar-coated to give sugar-coated tablets. Further, the tablet may be a single-layer tablet or a laminated tablet such as a two-layer tablet.

The liquid preparation can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, ethanol-containing purified water, etc.) as a carrier component, filtering or sterilizing if necessary, filling in a predetermined container, and sterilizing. .

The composition (or formulation) of the present invention is suitable for oral administration, and can be administered one or more times a day. The dose of the preparation per adult per day is, for example, about 1 to 300 mg, preferably 5 to 150 mg, more preferably 5 to 100 mg, particularly about 5 to 30 mg of free vitamin B1. When vitamin B6 is added, the daily dose of vitamin B6 in adult is, for example, 1 to 300 mg, preferably 10 to 100 mg in terms of free vitamin B6. The daily dose of vitamin B12 for adults is, for example, about 10 to 3000 µg, preferably about 50 to 1500 µg, in terms of free vitamin B12.

The dose of glucosamines (in terms of free glucosamine) is, for example, about 50 to 3000 mg, preferably 100 to 2500 mg, more preferably 300 to 2000 mg, particularly about 500 to 1500 mg per adult day.

Furthermore, the dosage of glycosaminoglycans such as chondroitin (as free glycosaminoglycans) is, for example, 0.01 to 10 g, preferably 0.1 to 5 g, more preferably 0.1 to 10 g per adult per day. It is about 1.5 g.

The composition of the present invention is, for example, a medicament effective for preventing or treating joint disorders such as arthritis and osteoarthritis causing joint pain by utilizing the activities of vitamins B1, glucosamines and glycosaminoglycans. It can be used as a formulation.

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

Example 1
Hydroxypropyl cellulose dissolved in purified water is added to a mixed powder obtained by mixing thiamine nitrate, glucosamine hydrochloride and crystalline cellulose until uniform, and the mixture is stirred and granulated. The dried and sized granulated powder is mixed with an equal mixture of potassium-magnesium L-aspartate, sodium chondroitin sulfate, croscarmellose sodium, light anhydrous silicic acid, and magnesium stearate, and stirred until uniform. The mixture was tableted with a rotary tableting machine to obtain circular tablets (8.5 mm in diameter, 270 mg in weight, and 5 kg in hardness (measured with a digital hardness meter)). The prescription of the tablet is shown below.

[Tablet prescription] ("parts" indicates "parts by weight"; the same applies hereinafter)
Thiamine nitrate 30mg
Chondroitin sodium sulfate 800mg
Glucosamine hydrochloride 1000mg
Equivalent mixture of potassium and magnesium aspartate 200mg
Hydroxypropyl cellulose 39mg
Crystalline cellulose suitable amount Magnesium stearate 12mg
Croscarmellose sodium 144mg
Light anhydrous silicic acid 24mg
Total 2400mg

Example 2 (vitamin B1 and vitamin C containing preparation)
A chewable (1300 mg per tablet) was produced using the following tablet formulation according to the Japanese Pharmacopoeia, General Rules for Preparation “Tablets”.
Amount (mg)
Thiamine nitrate 30mg
Chondroitin sodium sulfate 800mg
Glucosamine hydrochloride 1500mg
250mg ascorbic acid
Hydroxypropyl cellulose 77mg
Mannitol 1200mg
15mg aspartail
Menthol 8mg
Magnesium stearate 20mg
Total 3900mg

Example 3 (vitamin B1, vitamin B2 and vitamin B6 containing preparation)
Granules (1 packet = 1500 mg) were produced using the following formulation according to the Japanese Pharmacopoeia, General Rules for Preparations "Granules".
Amount (mg)
Thiamine hydrochloride 27mg
Chondroitin sodium sulfate 800mg
Glucosamine hydrochloride 1000mg
Riboflavin butyrate 12mg
Pyridoxine hydrochloride 12mg
Hydroxypropyl cellulose 110mg
1100mg crystalline cellulose
Mannitol 1430mg
Menthol 9mg
4500mg in total

Example 4 (Vitamin B1, Vitamin B6 and Vitamin B12-containing preparation)
Tablets (1 tablet = 280 mg) were produced using the following tablet formulation according to the Japanese Pharmacopoeia, General Rules for Preparation “Tablets”.
Amount (mg)
Fursultiamine hydrochloride 100mg
Chondroitin sodium sulfate 600mg
Glucosamine hydrochloride 900mg
Pyridoxine hydrochloride 100mg
Hydroxocobalamin 1.5mg
Hydroxypropylcellulose 18.5mg
787.5 mg of crystalline cellulose
Magnesium stearate 12.5mg
Total 2520mg

Example 5 (Vitamin B1 and Vitamin E containing preparation)
Tablets (1 tablet = 270 mg) were produced using the following tablet formulation according to the Japanese Pharmacopoeia, General Rules for Preparation “Tablets”.
Amount (mg)
Thiamine nitrate 30mg
Chondroitin sulfate sodium 500mg
Glucosamine hydrochloride 500mg
D-α-tocopherol acetate 12mg
73.6 mg of hydroxypropyl cellulose
700mg crystalline cellulose
Mannitol 600mg
2.4mg fragrance
Magnesium stearate 12mg
Total 2430mg

Example 6 (vitamin B1 and hyaluronic acid-containing preparation)
Tablets (1 tablet = 500 mg) were produced using the following tablet formulation according to the Japanese Pharmacopoeia, General Rules for Preparation “Tablets”.
Amount (mg)
Thiamine hydrochloride 24mg
Hyaluronic acid 450mg
Glucosamine hydrochloride 900mg
Hydroxypropyl cellulose 90mg
519mg crystalline cellulose
Lactose 1002mg
Magnesium stearate 15mg
Total 2995mg

Example 7
Tablets (1 tablet = 350 mg) were produced using the following tablet formulation according to the Japanese Pharmacopoeia, General Rules for Preparation “Tablets”.
Amount (mg)
Thiamine nitrate 2mg
Chondroitin sodium sulfate 400mg
Glucosamine sulfate 200mg
Hydroxypropyl cellulose 42mg
Mannitol 1446mg
Magnesium stearate 10mg
Total 2100mg

Test example 1
With respect to the test tablets 1 and 2 and the preparations of Examples 8 and 9 shown in Table 1, the joint pain improving effect was examined for each of 10 persons having knee joint pain in daily life due to deformation of the knee joint. The test tablets were prepared according to the formulation of Example 1 except that the amount of the active ingredient used was changed.

The test was carried out by taking the test tablets three times a day, three tablets each time, for 6 weeks, and comparing with the joint pain before taking the test tablets. The evaluation was made by scoring the degree of joint pain during walking, going up and down stairs, rising from a chair, and sitting straight. The degree of joint pain was scored based on the following criteria.

[Pain when walking]
Not painful: 0 points, painful when walking long distances: 1 point, painful even when walking short distances: 2 points [pain when going up and down stairs]
Easy to get up and down: 0 points, easy to get up and down using handrails: 1 point, step up and down: 2 points [Pain when rising from chair]
Does not hurt: 0 points, hurts if not supported by hand: 1 point, hurts even if supported by hand: 2 points [pain when sitting straight]
Can sit straight: 0 points, cannot sit down, but can sit sideways: 1 point, cannot sit sideways: 2 points For each item, the effect was evaluated by the difference between the total score of the 10 subjects before and after taking. That is, the larger the value of the difference Δ of the total points is, the higher the improvement effect is. Table 2 shows the results.

Furthermore, the degree of joint pain in the entire daily life was evaluated by VAS (Visual Analogue Scale). In other words, as the evaluation method, when the left end of the 10 cm scale is set to 0 with "no pain" at all and the right end is set to 100 with "the best pain that can be imagined", the degree of the perceived pain corresponds to The subject was pointed at one point on the scale, and the score of the indicated scale was checked. And the effect was evaluated by the difference of the total score of 10 people before and after taking.

As is clear from the above table, as a result of examining the improvement effect on joint pain by the degree of joint pain and VAS at the time of daily life movement of four items during walking, going up and down stairs, rising from a chair, and sitting straight, As compared with the preparation containing sodium chondroitin sulfate and glucosamine hydrochloride, the preparation of the present invention further containing vitamin B1 further improved joint pain in any of the items, and showed a high effect. In addition, it is shown that the limitation of the range of motion of the joint has been relaxed from the improvement of the joint pain during the daily activities, and the present invention was able to further relax the limit of the range of motion of the joint.

Furthermore, even when compared with a preparation containing vitamin B1 and sodium chondroitin sulfate, the preparation of the present invention further containing glucosamine showed a high effect.

Therefore, it was shown that the preparation of the present invention is useful for treating or preventing diseases such as osteoarthritis and arthritis that cause joint pain.

Claims (8)

(4) A composition comprising vitamin B1 and glucosamine, wherein the composition for treating or preventing arthralgia contains glucosamine in an amount of 0.1 to 1000 parts by weight per 1 part by weight of vitamin B1. (4) A composition for treating or preventing arthralgia comprising vitamin B1 and glucosamine, wherein the content of vitamin B1 is 0.001 to 30% by weight based on the whole. The composition for treating or preventing arthralgia according to claim 1 or 2, wherein the glucosamine is glucosamine or a salt thereof. 請求 The composition for treating or preventing joint pain according to claim 1, further comprising glycosaminoglycans. The composition for treating or preventing arthralgia according to claim 4, wherein the glycosaminoglycans are at least one selected from chondroitin, chondroitin sulfate and salts thereof. The composition for treating or preventing arthralgia according to claim 4, wherein the composition comprises 10 to 300 parts by weight of glycosaminoglycans based on 100 parts by weight of the total of vitamin B1 and glucosamine. Glucosamines are contained in an amount of 10 to 500 parts by weight with respect to 1 part by weight of vitamin B1 and glycosaminoglycans are contained in an amount of 30 to 200 parts by weight based on 100 parts by weight of the total amount of vitamin B1 and glucosamines. 5. The composition for treating or preventing arthralgia according to claim 4, comprising: The composition for treating or preventing arthralgia according to claim 1 or 2, further comprising at least one selected from vitamin B6 and vitamin B12.