JP2002145779A - Composition for treatment or prophylaxis of arthralgia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a pharmaceutical preparation useful for ameliorating arthropathy such as arthralgia. SOLUTION: The arthropathy such as arthralgia is ameliorated by combining vitamin B1s with glucosamines (glucosamine or its salt, etc.), in an amount of 1-1,000 pts.wt. of the glucosamines based on 1 pt.wt. of the vitamin B1s. Glycosaminoglycans (chondroitin, chondroitin sulfate or a salt, etc., thereof) in an amount of 10-300 pts.wt. based on 100 pts.wt. of the total amount of the vitamin B1s and the glucosamines may further be included in the resultant composition. Furthermore, vitamin B6s and/or vitamin B12s may further be included therein.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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

[0002]

2. Description of the Related Art A joint is easily inflamed because it is always mechanically stimulated by exercise. The 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, but joint pain is often caused as a subjective symptom thereof.

[0003] Vitamin B1s are used for Wernicke's encephalopathy, peripheral neuropathy, central nervous system disorders, neuralgia, muscle pain, joint pain (low back pain, stiff shoulders, fifty shoulders), numbness of limbs, eye strain, constipation, nutritional supplementation, etc. Used. The effects of vitamins B1 on joint pain are particularly effective for relatively mild joint pain symptoms such as lazy knee joints.

[0004] Regarding a solid preparation containing vitamin B1,
JP-A-5-27072 discloses a vitamin preparation comprising a succinic acid ester of tocopherol or a salt thereof, and vitamin B1 or ascorbic acid, and at least one of the components is coated with a coating agent. JP 2
000-247879 discloses a vitamin preparation containing a succinic acid ester of tocopherol or a salt thereof, vitamins B1 and a specific basic inorganic compound. Japanese Patent Application Laid-Open No. 9-268127 discloses that vitamin B
A solid formulation containing one derivative, starch and calcium hydrogen phosphate is disclosed. In addition, vitamin B1
Japanese Patent Application Laid-Open No. H5-255069 discloses an intravenous vitamin containing at least one selected from leucine, isoleucine, methionine and valine in a vitamin group containing at least one of 13 essential vitamins. A formulation is disclosed.

[0005] On the other hand, chondroitin is a biological macromolecule which is particularly distributed abundantly in cartilage tissue.
Sensorineural hearing loss (acoustic trauma), chronic nephritis, neuralgia, joint pain,
It is used for low back pain, periarthritis of the shoulder joint (fifty shoulders), adhesion prevention after laparotomy, and the like. Numerous pharmaceuticals containing sodium chondroitin sulfate have also been marketed or proposed.
For example, Japanese Patent Publication No. 9-503197 discloses a composition for treating connective tissues of humans and animals, which contains glycosaminoglycans such as chondroitin and amino sugars such as glucosamine. This composition has been used to prevent and treat joint pain with the recovery of connective tissue. JP-A-2000-53569 discloses, as a composition suitable for the prevention and treatment of joint disorders, a composition containing L-carnitine, glucosaminoglycan (such as chondroitin sulfate), glucosamine, and an excipient. It has been disclosed.

[0006] There is a need for a composition that is more effective in preventing and treating joint disorders such as joint pain.

[0007]

SUMMARY OF THE INVENTION 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 which 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.

[0009]

Means for Solving the Problems As a result of diligent studies to achieve the above object, the present inventors have found that joints obtained by combining vitamin B1s with glucosamines, especially with glycosaminoglycans such as chondroitin sulfate. The present inventors have found that they can relieve pain significantly and are effective in preventing or treating joint pain, and have 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 1 to 1000 parts of glucosamine is added to 1 part by weight of vitamin B1. Included in parts by weight. Further, the composition for treating or preventing joint pain of the present invention,
Vitamin B containing vitamins B1 and glucosamines
The content of Class 1 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 vitamins B1 and glucosamines. 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" refers to a composition for improving joint pain, a composition for preventing or treating joint disorders such as osteoarthritis or arthritis that cause joint pain. Is included.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION 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), and prosultiamine (TP
D), fursultiamine (TTFD), bisbenthamine (BTDS), sicotiamine (CCT), octiamine (TATD), alitiamine, thiamine propyl disulfide, thiamine tetrahydrofurfuryl disulfide (TPFD), dicetiamine (DCET), bisbutiamine, Bisbutiamine (DBT), thiamine monophosphate disulfide, thiamine pyrophosphate, shicotiamine, thiamine ethyl disulfide, thiamine propyl disulfide and the like can be exemplified. 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.

Among these vitamins B1, thiamine, thiamine disulfide, benfotiamine, fursultiamine, bisbenthamine, dicetiamine, thiamine ethyl disulfide and thiamine propyl disulfide are preferred from the viewpoint of stability. Particularly, bisbenthamine, fursultiamine and thiamine are preferred from the viewpoint of stability and absorbability.

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

The vitamins B1 may be used in combination with other vitamins. Examples of other vitamins include water-soluble vitamins [vitamin B2 (riboflavins such as sodium flavin adenine dinucleotide, riboflavin, sodium riboflavin phosphate, riboflavin butyrate), and vitamin B6 (vitamin B
6, pyridoxines such as pyridoxine and pyridoxal, physiologically acceptable salts (hydrochlorides such as pyridoxine hydrochloride, corresponding acetates and phosphates such as pyridoxal phosphate), vitamin B12s (vitamin B1
2. Vitamin Bs such as mecobalamin, cyanocobalamin, hydroxocobalamin, cobalamin such as methylcobalamin, or physiologically acceptable salts thereof (hydrochloride, acetate such as hydroxocobalamin acetate);
Vitamin Cs (ascorbic acid, calcium ascorbate, sodium ascorbate, etc.), nicotinic acids (nicotinic acid, nicotinamide, etc.), pantothenic acids (panthenol, pantothenic acid or a salt thereof),
Biotin, folic acid, etc.], fat-soluble vitamins [vitamin A
(Retinol acetate, retinol palmitate, vitamin A oil, etc.), vitamin D (ergocalciferol, cholecalciferol, etc.), vitamin E (liver oil, strong liver oil, d-α-tocopherol acetate, dl-acetate)
α-tocopherol, d-α-tocopherol, dl-
α-tocopherol), vitamin K, etc.]. These vitamins can 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 C, 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 vitamins B1 and other vitamins is 100/0 to 20/80,
Preferably, it may be selected from the range of about 100/0 to 30/70, more preferably about 100/0 to 50/50.

In the present invention, by combining vitamin B1 and glucosamine, 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.

The glucosamines include, for example, glucosamine, glucosamine salts (physiologically acceptable salts such as hydrochloride and sulfate, and inorganic salts such as glucosamine hydrochloride, glucosamine sulfate and glucosamine phosphate). And glucosamine derivatives (eg, N-acetylglucosamine, N-methyl-L-glucosamine) and the like. 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).

[0019] Glucosamine or a salt thereof, which is a typical amino sugar, can be obtained by purifying shrimp, crab, squid, etc. by enzymatic or hydrolysis treatment, and commercially available products 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% by weight). 99.9% by weight), preferably 10 to 9
0% by weight, 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, 0.001 to 10 w / v%, preferably 0.01%
-10 w / v%, more preferably 0.01-5 w / v
%.

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

In the present invention, the use of glycosaminoglycans (mucopolysaccharide or acidic mucopolysaccharide) can further improve the physiological activity or pharmacological activity against joint disorders. Also, in solid preparations, glucosamines can significantly suppress the formation of gels due to glycosaminoglycans,
Disintegration can be improved. Therefore, when the present invention is applied to a solid preparation containing glycosaminoglycans, the activity of vitamin B1 and glucosamine can be effectively expressed. Further, disintegration in the digestive tract is promoted without being affected by fluctuations in pH, and the active ingredient can be stably released. For example, when the pH is about 1 to 10 (for example, about 1 to 10)
The disintegration of the solid preparation can be greatly improved even if it fluctuates in the range of about 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. As salts of glycosaminoglycans, alkali metal salts (such as sodium salts such as sodium hyaluronate), sulfated glucosaminoglycans (chondroitin sulfate A (chondroitin 4-
Sulfuric acid), chondroitin sulfate B (dermatan sulfate), chondroitin sulfate C (chondroitin 6-sulfate), heparin, heparan sulfate, keratan sulfate I, keratan sulfate II, and the like. The sulfated glucosaminoglycan may be a metal salt such as sodium, potassium, calcium, magnesium, iron and manganese, or a salt such as an 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 a natural product such as collagen, and a commercially available product 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 terms of safety and absorbability.

The amount of glycosaminoglycans such as chondroitin sulfate is 0.5 to 90% based on the whole composition.
% By weight. For example, the amount of glycosaminoglycans is 1 to 90% by weight, preferably 5 to 80% by weight, more preferably 10 to 70% by weight, and usually 10 to 70% by weight. ~ 60% by weight, preferably 10-5%
It is about 0% by weight.

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

If necessary, the pharmaceutical composition of the present invention may contain other physiologically active ingredients or pharmacologically active ingredients such as analgesics for joints and muscles (analgesic and antipyretics such as acetaminophen, ibuprofen, salicylic acid derivatives, mefenamic acid, etc.) Agents, antihistamines, etc.), aminoethylsulfonic acid, γ-oryzanol, crude drug components (processed garlic, carrot, yoquinin, etc.), inorganic salts (potassium / magnesium aspartate equivalent mixture, calcium glycerophosphate, calcium gluconate, precipitated calcium carbonate, Calcium lactate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, caffeine (caffeine, anhydrous caffeine, etc.), amino acid or its salt (L-cysteine, L-cysteine hydrochloride, etc.), glucuronolactone, glucuron Acids, minerals, etc. It may have.

Further, the dosage form of the preparation of the present invention is not particularly limited, and liquids (suspension, emulsion, syrup, injection, etc.)
Or solid preparations (powder, fine granule, granule, pill, capsule, tablet, etc.).

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 is not impaired. In solid formulations,
Examples of the carrier component or additive include excipients (sugar alcohols such as D-sorbitol, D-mannitol, xylitol, sugars such as glucose, sucrose, lactose, and fructose;
Microcrystalline cellulose, carmellose sodium, calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β
-Cyclodextrin, light silicic anhydride, titanium oxide,
Disintegrators (low-substituted hydroxypropylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, hydroxypropyl starch,
Binders (eg, cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose), polyvinylpyrrolidone, polyvinylalcohol, acrylic polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar Lubricating 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 agents (hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose) , Hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinylacetal diethylaminoacetate,
Aminoalkyl methacrylate copolymer, hydroxypropyl methylcellulose acetate succinate,
Coloring agents (turmeric extract, riboflavin, titanium oxide, carotene solution, etc.); flavoring agents (aspartame, ascorbic acid, stevia, menthol, licorice extract, single syrup) Surfactants (polyoxyethylene hydrogenated castor oil,
Glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, macrogol, sucrose fatty acid ester, etc.); plasticizers (triethyl citrate, polyethylene glycol, triacetin) , Cetanol, etc.); sweeteners (natural or synthetic sweeteners such as sucrose, mannitol, aspartame); flavoring agents (such as menthol);
Preservatives, wetting agents, antistatic agents and the like can be mentioned.

In the liquid preparation, water or alcohol-containing water can usually be used as a carrier component, and can be formulated using conventional components. Examples of the additive 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, Turbidity agents (kaolin, carmellose sodium, xanthan gum, methylcellulose, tragacanth, etc.), antifoaming agents (dimethylpolysiloxane, silicone antifoaming agent, etc.), thickeners (xanthan gum,
Tragacanth, methylcellulose, dextrin, etc.),
Solubilizing agents (ethanol, sucrose fatty acid ester, macrogol, etc.), the above-mentioned antioxidants, coloring agents, sweetening agents, flavoring agents and the like can be exemplified.

The composition of the present invention (pharmaceutical composition) 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 component (eg, excipient) and compression-molding the mixture. further,
Granules such as granules among solid preparations can be prepared by various granulation methods (extrusion granulation, pulverization granulation, dry compaction granulation, fluidized bed granulation, tumbling granulation, high-speed stirring granulation). Tablet) may be prepared by the above granulation method, tableting method (wet tableting method,
Direct tableting method) can be prepared in an appropriate combination. Furthermore, capsules can be prepared by powdering and granulating (powder, granules, etc.) in capsules (soft or hard capsules) by a conventional method.
Can be prepared. The preferred dosage form of the solid preparation is a tablet (eg, 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 is 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. Can be prepared.

The composition (or preparation) of the present invention is suitable for oral administration, and can be administered one or more times a day. The daily dose of the preparation per adult is, for example, 1 to 300 mg, preferably 5 to 150 mg of free vitamin B1.
mg, more preferably 5 to 100 mg, particularly 5 to 30 mg
mg. When vitamin B6 is added, the daily dose of vitamin B6 for adults is 1 to 300 mg, preferably 10 to 100 mg, in terms of free vitamin B6. The daily dose of vitamin B12 per adult is, for example, 10 to 3000 μg, preferably 5
It is about 0 to 1500 μg.

The dose of glucosamine (in terms of free glucosamine) is, for example, 50 to 3 per adult per day.
000 mg, preferably 100 to 2500 mg, more preferably 300 to 2000 mg, especially 500 to 150 mg
It is about 0 mg.

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

The composition of the present invention comprises, for example, vitamin B1
, Glucosamines, and glycosaminoglycans can be used as a pharmaceutical preparation effective for preventing or treating joint disorders such as arthritis and osteoarthritis that cause joint pain.

[0038]

According to the present invention, since vitamin B1s and glucosamines are combined, they are useful for preventing or treating arthralgia. 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.

[0039]

The present invention will be described below in more detail with reference to Examples, but the present invention is not limited to these Examples.

Example 1 Hydroxypropylcellulose 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 granulated with stirring. The dried and sized granulated powder is mixed with an equal mixture of potassium and 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 (diameter 8.5 mm, weight 270 mg, hardness 5 kg (measured with a digital hardness meter)). The prescription of the tablet is shown below.

[Tablet Formulation] ("Parts" means "parts by weight". The same applies hereinafter.) Thiamine nitrate 30 mg Chondroitin sulfate 800 mg Glucosamine hydrochloride 1000 mg Equivalent mixture of potassium and magnesium aspartate 200 mg Hydroxypropyl cellulose 39 mg Crystalline cellulose Appropriate 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 preparation (1300 mg per tablet) was prepared using the following tablet formulation according to the Japanese Pharmacopoeia, General Rules for Preparation “Tablets”. Amount (mg) Thiamine nitrate 30mg Chondroitin sulfate 800mg Glucosamine hydrochloride 1500mg Ascorbic acid 250mg Hydroxypropyl cellulose 77mg Mannitol 1200mg Aspartale 15mg Menthol 8mg Magnesium stearate 20mg Total 3900mg

Example 3 (Preparation of Vitamin B1, Vitamin B2 and Vitamin B6) Granules (1 packet = 1500 mg) were produced according to the following prescription according to the Japanese Pharmacopoeia, General Rules for Preparation "Granules". Amount (mg) Thiamine hydrochloride 27 mg Chondroitin sulfate 800 mg Glucosamine hydrochloride 1000 mg Riboflavin butyrate 12 mg Pyridoxine hydrochloride 12 mg Hydroxypropyl cellulose 110 mg Crystalline cellulose 1100 mg Mannitol 1430 mg Menthol 9 mg Total 4500 mg

Example 4 (Vitamin B1, Vitamin B6 and Vitamin B12-Containing Formulation) 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 100 mg Chondroitin sulfate 600 mg Glucosamine hydrochloride 900 mg Pyridoxine hydrochloride 100 mg Hydroxocobalamin 1.5 mg Hydroxypropyl cellulose 18.5 mg Crystalline cellulose 787.5 mg Magnesium stearate 12.5 mg Total 2520 mg

Example 5 (Vitamin B1 and Vitamin E-Containing Formulation) 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 500mg Glucosamine hydrochloride 500mg d-α-tocopherol acetate 12mg Hydroxypropylcellulose 73.6mg Crystalline cellulose 700mg Mannitol 600mg Flavor 2.4mg Magnesium stearate 12mg Total 2430mg

Example 6 (Vitamin B1 and Hyaluronic Acid-Containing Formulation) Tablets (1 tablet = 500 mg) were produced using the following tablet formulation according to the Japanese Pharmacopoeia, General Rules for Preparation “Tablets”. Compounding amount (mg) Thiamine hydrochloride 24 mg Hyaluronic acid 450 mg Glucosamine hydrochloride 900 mg Hydroxypropyl cellulose 90 mg Crystalline cellulose 519 mg Lactose 1002 mg Magnesium stearate 15 mg Total 2995 mg

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 Hydroxypropylcellulose 42mg Mannitol 1446mg Magnesium stearate 10mg Total 2100mg

Test Example 1 Test tablets 1 and 2 and the preparations of Examples 8 and 9 shown in Table 1 were subjected to joint pain in 10 persons who had knee joint pain in daily life due to deformation of the knee joint. The improvement effect was examined. 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 them with the joint pain before taking the test tablets. The evaluation was performed 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] Painless: 0 points, painful when walking long distances: 1 point, painful even when walking short distances: 2 points [Pain when climbing up and down stairs] Easy to climb up and down: 0 points, handrail You can easily get up and down using: 1 point, step up and down: 2 points [Pain when rising from a chair] Not painful: 0 points, painful if not supported by hand: 1 point, supported by hand Pain: 2 points [Pain when sitting] Seated: 0 points, unable to sit down, but able to sit sideways: 1 point, unable to sit sideways: 2 points Total of 10 items before and after taking each item The effect was evaluated by the difference in points. 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.

Further, the degree of joint pain in the whole 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 at “no pain” at all and the right end is set to 100 at “maximum 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. The effect was evaluated by the difference between the total score of the 10 subjects before and after taking the drug.

[0052]

[Table 1]

[0053]

[Table 2]

As is clear from the above table, the degree of joint pain during daily activities of walking, walking up and down stairs, standing up from a chair, and sitting in a sitting position and the effect of VAS on improving joint pain are examined. As a result, 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 was also eased due to the improvement of the joint pain during the daily life operation, and the present invention was able to further ease the limit of the range of motion of the joint.

Further, 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 which cause joint pain.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 19/02 A61P 19/02 // C07D 415/00 C07D 415/00 (72) Inventor Tomoharu Nishimori Osaka 1-8-1, Tatsuminishi, Ichino-ku, Tokyo F-Term (in reference) 4C063 AA01 BB02 CC62 DD29 EE01 4C086 AA01 AA02 BC18 BC83 DA39 EA22 EA26 GA07 GA10 MA02 MA03 MA04 NA14 ZA96

Claims (8)

[Claims] 1. A composition comprising vitamin B1 and glucosamine, for treating or preventing arthralgia containing glucosamine in an amount of 0.1 to 1000 parts by weight per 1 part by weight of vitamin B1. Composition. 2. It contains vitamin B1 and glucosamine, and the content of vitamin B1 is 0.001 to the whole.
A composition for treating or preventing joint pain, which is 〜30% by weight. 3. The composition for treating or preventing arthralgia according to claim 1, wherein the glucosamine is glucosamine or a salt thereof. 4. The composition for treating or preventing joint pain according to claim 1, further comprising glycosaminoglycans. 5. 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. 6. Glycosaminoglycans are added to 10 parts by weight of the total amount of vitamin B1 and glucosamine.
The composition for treating or preventing arthralgia according to claim 4, wherein the composition comprises -300 parts by weight. 7. Glucosamines are contained in a proportion of 10 to 500 parts by weight per 1 part by weight of vitamin B1 and glycosaminoglycans are contained in an amount of 30 to 500 parts by weight based on 100 parts by weight of the total of vitamin B1 and glucosamine. The composition for treating or preventing arthralgia according to claim 4, comprising 200 parts by weight. 8. The method according to claim 1, further comprising at least one selected from vitamin B6 and vitamin B12.
Or the composition for treating or preventing joint pain according to 2 or 3.