JP2015180687A - Composition for treatment or prevention of arthralgia - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a formulation composition useful for ameliorating arthropathy such as arthralgia.SOLUTION: The arthropathy such as arthralgia is ameliorated by combining vitamin B1s with glucosamines (glucosamine or a salt thereof and the like) in an amount of 1-1,000 parts by weight of the glucosamines based on 1 part by weight of the vitamin B1s. Glycosaminoglycans (a chondroitin, a chondroitin sulfate, or a salt thereof and the like) in an amount of 10-300 parts by weight based on 100 parts by weight of the total amount of the vitamin B1s and the glucosamines may further be contained in this composition. Furthermore, vitamin B6s and/or vitamin B12s may be contained.

Description

The present invention relates to a composition for prevention or treatment of joint disorders comprising vitamin B1s, glucosamines and optionally glycosaminoglycans.

Since joints are always mechanically stimulated by exercise, they are easily prone to inflammation.
There are various causes of inflammation, such as joint deformation, bacterial / viral infection, trauma, immune diseases such as allergies, or metabolic abnormality due to nephritis, etc., but joint pain is often caused as a subjective symptom.

Vitamin B1 is used for Wernicke's encephalopathy, peripheral neuropathy, central neuropathy, neuralgia, muscle pain, joint pain (back pain, stiff shoulders, fifty shoulders), numbness in the limbs, treatment of eye strain, constipation, nutritional supplements, etc. Yes. The effect of vitamin B1 on arthralgia is particularly effective for relatively mild arthralgia symptoms such as a knee joint being lazy.

Regarding a solid preparation containing vitamin B1, JP-A-5-271072 (Patent Document 1)
Discloses a vitamin preparation containing tocopherol succinate or a salt thereof, vitamin B1 or ascorbic acid, and at least one of which is coated with a coating agent. Japanese Unexamined Patent Publication No. 2000-247879 (patent document 2) discloses a vitamin preparation containing a succinic acid ester of tocopherol or a salt thereof, vitamin B1s, and a specific basic inorganic compound. JP-A-9-268127 (Patent Document 3) discloses vitamin B.
A solid formulation containing a derivative, starch and calcium hydrogen phosphate is disclosed.
Furthermore, regarding the liquid agent containing vitamin B1, Unexamined-Japanese-Patent No. 5-255069 (patent document 4)
Discloses a vitamin preparation for intravenous injection containing at least one selected from leucine, isoleucine, methionine and valine in a vitamin group containing at least one of 13 essential vitamins.

On the other hand, chondroitin is a biopolymer that is particularly distributed in cartilage tissue, and protects the corneal surface layer, sensorineural hearing loss (acoustic trauma), chronic nephritis, neuralgia, arthralgia, low back pain, peri-shoulderitis ( Fifty shoulders), used to prevent adhesion after laparotomy. Numerous pharmaceuticals containing sodium chondroitin sulfate are also commercially available or proposed. For example, special table hei 9-503197
No. (Patent Document 5) discloses a composition for treating human or animal connective tissue, which contains glycosaminoglycans such as chondroitin and amino sugars such as glucosamine. This composition has been utilized to prevent and treat joint pain with the recovery of connective tissue. In JP 2000-53569 A (Patent Document 6), L-carnitines, glucosaminoglycans (such as chondroitin sulfate), glucosamine and excipients are used as compositions suitable for the prevention and treatment of joint disorders. Compositions containing are disclosed.

There is a need for a composition that is more effective for the prevention and treatment of joint disorders such as joint pain.

Japanese Patent Laid-Open No. 5-271072 JP 2000-247879 A JP-A-9-268127 JP-A-5-255069 Japanese National Patent Publication No. 9-503197 JP 2000-53569 A

An object of the present invention is to provide a pharmaceutical composition useful for the prevention or treatment of 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 expanding the range of motion (or range of motion) of the joint.

As a result of diligent studies to achieve the above-mentioned problems, the present inventor can relieve joint pain significantly by combining vitamin B1 and glucosamine, particularly a combination of glycosaminoglycans such as chondroitin sulfate. The present invention has been completed by finding out that it is effective for the prevention or treatment of.

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 by weight of glucosamine is 1 part by weight of vitamin B1. Include in percentage. The composition for treating or preventing joint pain of the present invention comprises:
Vitamin B1 and glucosamine are included, and the content of vitamin B1 is 0.
001 to 30% by weight. These compositions may further contain glycosaminoglycans. As the glucosamines, glucosamine or a salt thereof can be used,
As glycosaminoglycans, chondroitin, chondroitin sulfate or a salt thereof can be used. About 10-300 weight part may be sufficient as the ratio of glycosaminoglycans with respect to 100 weight part of total amounts of the said vitamin B1 and glucosamine. The pharmaceutical composition of the present invention may further contain vitamin B6s and / or vitamin B12s.

In the present specification, “a composition for treating or preventing joint pain” refers to a composition for improving joint pain,
Compositions for preventing or treating joint disorders such as osteoarthritis or arthritis that cause joint pain are included.

That is, the present invention provides the following.
Item 1. A composition containing vitamin B1 and glucosamine, the composition for treating or preventing joint pain comprising 0.1 to 1000 parts by weight of glucosamine with respect to 1 part by weight of vitamin B1.
Item 2. A composition for treating or preventing joint pain, comprising vitamin B1 and glucosamine, wherein the content of vitamin B1 is 0.001 to 30% by weight based on the whole.
Item 3. Item 3. The composition for treating or preventing joint pain according to Item 1 or 2, wherein the glucosamine is glucosamine or a salt thereof.
Item 4. The composition for treating or preventing joint pain according to Item 1, further comprising glycosaminoglycans.
Item 5. Item 5. The composition for treating or preventing joint pain according to Item 4, wherein the glycosaminoglycans are at least one selected from chondroitin, chondroitin sulfate and salts thereof.
Item 6. Item 5. The composition for treating or preventing joint pain according to Item 4, comprising 10 to 300 parts by weight of glycosaminoglycans with respect to 100 parts by weight of the total amount of vitamin B1 and glucosamine.
Item 7. A ratio of 10 to 500 parts by weight of glucosamine with respect to 1 part by weight of vitamin B1, and a ratio of 30 to 200 parts by weight of glycosaminoglycan with respect to 100 parts by weight of the total amount of vitamin B1 and glucosamine Item 5. The composition for treating or preventing joint pain according to Item 4,
Item 8. Item 3. The composition for treating or preventing joint pain according to Item 1 or 2, further comprising at least one selected from vitamin B6 and vitamin B12.

In the present invention, since vitamin B1 and glucosamine are combined, it is useful for prevention or treatment of joint pain. In addition, joint pain can be effectively improved, and the range or range of motion of the joint can be expanded.
Furthermore, it is more effective to contain glycosaminoglycans.

The vitamin B1 contained in the composition of the present invention includes thiamine, thiamine derivatives, and salts thereof, and the thiamine derivative may be disulfide type, acyl type, or the like. As thiamine derivatives, for example, bithiamine, thiamine disulfide (TDS),
Thiamine dicetyl sulfate, benfotiamine (BTMP), prosultiamine (
TPD), fursultiamine (TTFD), bisbentiamine (BTDS), chicotiamine (CCT), octothiamine (TATD), alithiamine, thiaminepropyl disulfide, thiaminetetrahydrofurfuryl disulfide (TPFD), dicetiamine (DC)
ET), bisbutiamine, bisbutiamine (DBT), thiamine monophosphate disulfide, thiamine pyrophosphate, chicotiamine, thiamine ethyl disulfide, thiamine propyl disulfide and the like. Examples of thiamine salts include physiologically acceptable salts, for example, hydrochlorides such as thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, dicetiamine hydrochloride, and fursultiamine hydrochloride, and nitrates. These vitamin B1s can be used alone or in combination of two or more.

Among these vitamin B1s, thiamine, thiamine disulfide,
Benfotiamine, fursultiamine, bisbenchamine, dicetiamine, thiamine ethyl disulfide, and thiamine propyl disulfide are preferred. In particular, bisbenchamine, fursultiamine, and thiamine are preferable from the viewpoint of stability and absorbability.

The amount of vitamin B1 compounded is, for example, 0.001 to the entire preparation (particularly solid preparation).
It can be selected from the range of about 30% by weight, preferably 0.01 to 20% by weight, more preferably about 0.1 to 10% by weight, and is usually about 0.1 to 5% by weight. In solution, vitamin B
The content of Class 1 is usually preferably about 0.0002 to 0.03 w / v% with respect to the whole.

Vitamin B1 may be used in combination with other vitamins. Other vitamins include, for example, water-soluble vitamins [vitamin B2 (riboflavins such as flavin adenine dinucleotide sodium, riboflavin, sodium riboflavin phosphate, riboflavin butyrate), vitamin B6 (vitamin B6, pyridoxine, pyridoxal, etc. Pyridoxines, physiologically acceptable salts (hydrochlorides such as pyridoxine hydrochloride, corresponding acetates, phosphates such as pyridoxal phosphate), vitamin B12 (vitamin B12, mecobalamin, cyanocobalamin, hydroxocobalamin, Vitamin Bs such as cobalamins such as methylcobalamin, or physiologically acceptable salts thereof (hydrochloride, acetates such as hydroxocobalamin acetate), vitamin Cs (ascorbic acid, calcium ascorbate) , Sodium ascorbate), nicotinic acid (nicotinic acid,
Nicotinamide, etc.), pantothenic acids (pantenol, pantothenic acid or its salts, etc.), 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, acetic acid d-α-tocopherol, dl-α-tocopherol acetate, d-α-tocopherol, dl-α-tocopherol, etc.), vitamins K etc.] can be exemplified. 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. Of the vitamin B6 types, pyridoxine is preferable, and the vitamin B
Of the 12 types, cyanocobalamin or hydroxocobalamin is preferred. In order to improve or reduce joint pain in an overall advantageous manner, it is preferably used in combination with vitamins C, vitamins B6 and / or vitamins B12.

The ratio (weight ratio) between vitamin B1 and other vitamins is the former / the latter = 100/0 to 2
0/80, preferably 100/0 to 30/70, more preferably 100/0 to 50/5
You may select from the range of about zero.

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

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), glucosamine derivatives (N-acetylglucosamine, N-methyl-L-glucosamine, etc.) can be exemplified. Glucosamines are D,
L or DL form may be sufficient. These glucosamines can be used alone or in combination of two or more. A preferred glucosamine is 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 and the like by enzyme or hydrolysis treatment, and commercially available products can also be used.

The compounding quantity of glucosamines, such as glucosamine, can be selected from the wide range of about 1-99.9 weight% with respect to the whole solid formulation, and is 5-99.9 weight% normally (for example, 7.5-99.
9 wt%), preferably 10 to 90 wt%, more preferably about 10 to 80 wt%. The compounding quantity of glucosamine is normally about 10 to 60 weight%. The content of glucosamines in the liquid is, for example, 0.001 to 10 w / v%, preferably 0.01 to 10 w / v.
%, More preferably about 0.01 to 5 w / v%.

The proportion of glucosamines relative to vitamin B1 may be an effective amount that can improve joint pain. For example, 0.1 to 1000 parts by weight, preferably 1 to 500 parts by weight of glucosamine with respect to 1 part by weight of vitamin B1 More preferably, it is about 1 to 300 parts by weight. The amount of glucosamine used is usually about 1 to 100 parts by weight, particularly about 2 to 50 parts by weight, based on 1 part by weight of vitamin B1.

In the present invention, when glycosaminoglycans (mucopolysaccharides or acidic mucopolysaccharides) are further used, the physiological activity or pharmacological activity against joint disorders can be further improved. In addition, in solid preparations, glucosamines can remarkably suppress the formation of gels by glycosaminoglycans,
Disintegration can be improved. Therefore, when the present invention is applied to a solid preparation containing glycosaminoglycans, the activities of vitamin B1s and glucosamines can be effectively expressed. Furthermore, it is possible to promote the disintegration in the gastrointestinal tract and to release the active ingredient stably without being affected by the change in pH. For example, even if the pH varies in the range of about 1 to 10 (for example, about 1 to 7), particularly in a low pH range (for example, about 1 to 4), the disintegration property of the solid preparation can be greatly improved. Therefore, even if the intragastric pH varies within 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 containing glucosamines, for example,
Hyaluronic acid, chondroitin, jalluronic acid, heparan, keratan or salts thereof are included. As salts of glycosaminoglycans, alkali metal salts (sodium salts such as sodium hyaluronate), sulfated glucosaminoglycans (chondroitin sulfate A)
(Chondroitin 4-sulfate), chondroitin sulfate B (dermatan sulfate), chondroitin sulfate such as 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, manganese, 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). In particular, chondroitin or chondroitin sulfate or a salt thereof is preferable.

Chondroitin or a salt thereof can be obtained from natural products such as animal cartilage or collagen, and commercially available products can also be used. In addition to purified chondroitin, it can also be used as animal cartilage powder or extract / extract containing chondroitin or a salt thereof. The salts may be physiologically acceptable salts such as hydrochlorides and sulfates. Purified chondroitin or chondroitin sulfate or a salt thereof is more preferable in terms of safety and absorbability.

The blending amount of glycosaminoglycans such as chondroitin sulfate is 0 with respect to the entire composition.
. It can be selected from a wide range of about 5 to 90% by weight, for example, the amount of glycosaminoglycans is 1 to 90% by weight, preferably 5 to 80% by weight, more preferably about 10 to 70% by weight, Usually, it is about 10 to 60% by weight, preferably about 10 to 50% by weight.

The amount of glycosaminoglycans (such as chondroitin sulfate) used is, for example, vitamin B
It can be selected from a wide range of about 1 to 500 parts by weight with respect to 100 parts by weight of the total amount of Class 1 and glucosamines. The amount of glucosamines 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 parts per 100 parts by weight of the total amount of vitamin B1 and glucosamines. About 150 parts by weight.

The pharmaceutical composition of the present invention contains other physiologically active ingredients and pharmacologically active ingredients as necessary, for example, joint and muscle analgesics (analgesic antipyretic agents such as acetaminophen, ibuprofen, salicylic acid derivatives, mefenamic acid, anti-inflammatory agents, antihistamines, etc. Etc.), aminoethylsulfonic acid, γ-oryzanol, herbal medicine ingredients (processed potato, carrot, yokuinin, etc.), inorganic salts (equivalent mixture of potassium aspartate and magnesium, calcium glycerophosphate, 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,
It may contain minerals.

Furthermore, the dosage form of the preparation of the present invention is not particularly limited, and is a liquid preparation (suspension, emulsion, syrup, injection, etc.) or solid preparation (powder, fine granules, granules, pills, capsules). Or tablets).

The preparation of the present invention can be prepared by a conventional method by adding a conventional carrier component depending on the form of the preparation as long as the stability and the like are not impaired. In solid preparations, carrier components or additives include, for example, excipients (sugar alcohols such as D-sorbitol, D-mannitol, xylitol, sugars such as glucose, sucrose, lactose, fructose, crystalline cellulose, carmellose sodium, Calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminate metasilicate, talc, kaolin, etc .; disintegrant (low substitution degree) Hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, partially pregelatinized starch, etc.);
Binders (cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic polymers, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, alginic acid Propylene glycol esters, etc.) Lubricants (stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, white 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, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, hydroxypropylmethylcellulose acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate, Coloring agents (turmeric extract, riboflavin, titanium oxide, carotene solution, etc.); flavoring agents (aspartame, ascorbic acid, stevia, menthol, licorice crude extract, simple syrup, etc.);
Surfactants (polyoxyethylene hydrogenated castor oil, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, macrogols, sucrose fatty acid esters, etc.); Plasticizers (triethyl citrate, polyethylene glycol, triacetin, cetanol, etc.); sweeteners (natural or synthetic sweeteners such as sucrose, mannitol, aspartame); flavoring agents (eg menthol); adsorbents, preservatives, wetting agents And antistatic agents.

In liquid preparations, water or alcohol-containing water can be usually 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, mint water, etc.), the surfactant, Turbidizing agents (kaolin, carmellose sodium, xanthan gum, methylcellulose, tragacanth, etc.), antifoaming agents (dimethylpolysiloxane, silicon antifoaming agents, etc.), thickeners (xanthan gum, tragacanth, methylcellulose, dextrin, etc.), solubilizing agents (Ethanol, sucrose fatty acid ester, macrogol, etc.), the above antioxidants, colorants, sweeteners, flavoring agents and the like.

The composition (formulation composition) of the present invention can be obtained by applying a conventional method in the technical field as it is or appropriately. For example, in the case of a tablet, it can be prepared by mixing a powdery active ingredient and a pharmaceutically acceptable carrier component (excipient etc.) and compression molding. further,
Among the solid preparations, granules such as granules are available in various granulation methods (extrusion granulation method, pulverization granulation method, dry compaction granulation method, fluidized bed granulation method, rolling granulation method, high-speed stirring granulation method). The tablet may be prepared by appropriately combining the above granulation method, tableting method (wet tableting method, direct tableting method) and the like. Furthermore, the capsule can be prepared by filling a capsule (soft or hard capsule) with a powder (powder, granule, etc.) by a conventional method. A preferable dosage form of the solid preparation is a tablet (for example, a chewable tablet in the mouth). The tablets are given a sugar coating,
Dragees may be used. Furthermore, the tablet may be a monolayer tablet or a laminated tablet such as a bilayer tablet.

The liquid preparation can be prepared by dissolving or dispersing each component in an aqueous medium as a carrier component (purified water, ethanol-containing purified water, etc.), filtering or sterilizing as necessary, filling 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 per day. The dosage of the preparation per day for adults is, for example, 1 to 3 as free vitamin B1s.
00 mg, preferably 5-150 mg, more preferably 5-100 mg, especially 5-30
It is about mg. When blending vitamin B6, the dose of vitamin B6 per adult day is, for example, 1 to 300 mg, preferably 10 to 1 in terms of free vitamin B6.
00 mg. Moreover, the dose of vitamin B12 per day for an adult is, for example, about 10 to 3000 μg, preferably about 50 to 1500 μg in terms of free vitamin B12.

The dosage of glucosamines (in terms of free glucosamine) is, for example, 50 to 3000 mg, preferably 100 to 2500 mg, more preferably 300 to 2 per day for an adult.
000 mg, especially about 500 to 1500 mg.

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

The composition of the present invention is, for example, a pharmaceutical effective for the prevention or treatment of joint disorders such as arthritis causing osteoarthritis and osteoarthritis using the activity of vitamins B1, glucosamines and glycosaminoglycans. It can be used as a preparation.

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 granulated with stirring. To a granulated powder that has been dried and sized, a mixture of an equal amount of potassium L-aspartate / magnesium, sodium chondroitin sulfate, croscarmellose sodium, light anhydrous silicic acid, and magnesium stearate is mixed and stirred until uniform. The mixture was tableted with a rotary tableting machine, and a circular tablet (diameter 8.5 mm, weight 270 mg, hardness 5 kg (measured with a digital hardness meter))
Got. The tablet formulation is shown below.

[Tablet prescription] ("Part" indicates "part by weight". The same applies hereinafter)
30 mg of thiamine nitrate
Sodium chondroitin sulfate 800mg
Glucosamine hydrochloride 1000mg
Potassium aspartate / magnesium equivalent mixture 200mg
Hydroxypropylcellulose 39mg
Crystalline cellulose appropriate amount Magnesium stearate 12mg
Croscarmellose sodium 144mg
Light anhydrous silicic acid 24mg
Total 2400mg

Example 2 (formulation containing vitamin B1 and vitamin C)
A chewable preparation (1 tablet 1300 mg) was produced using the following tablet formulation according to the Japanese Pharmacopoeia, General Formulation “Tablet”.
Compounding amount (mg)
30 mg of thiamine nitrate
Sodium chondroitin sulfate 800mg
Glucosamine hydrochloride 1500mg
Ascorbic acid 250mg
Hydroxypropylcellulose 77mg
Mannitol 1200mg
Aspartale 15mg
Menthol 8mg
Magnesium stearate 20mg
Total 3900mg

Example 3 (formulation containing vitamin B1, vitamin B2 and vitamin B6)
In accordance with the Japanese Pharmacopoeia, General Formulation “Granules”, the following prescription is used and granules (1 capsule = 150
0 mg) was produced.
Compounding amount (mg)
Thiamine hydrochloride 27mg
Sodium chondroitin sulfate 800mg
Glucosamine hydrochloride 1000mg
Riboflavin butyrate 12mg
Pyridoxine hydrochloride 12mg
Hydroxypropylcellulose 110mg
Crystalline cellulose 1100mg
Mannitol 1430mg
Menthol 9mg
Total 4500mg

Example 4 (formulation containing vitamin B1, vitamin B6 and vitamin B12)
According to the Japanese Pharmacopoeia, General Formulation “Tablets”, the following tablet formulation is used and tablets (1 tablet = 280)
mg).
Compounding amount (mg)
Fursultiamine hydrochloride 100mg
Sodium chondroitin sulfate 600mg
Glucosamine hydrochloride 900mg
Pyridoxine hydrochloride 100mg
Hydroxocobalamin 1.5mg
Hydroxypropylcellulose 18.5mg
Crystalline cellulose 787.5mg
Magnesium stearate 12.5mg
Total 2520mg

Example 5 (vitamin B1 and vitamin E-containing preparation)
According to the Japanese Pharmacopoeia, General Rules for Tablets “Tablets”, the following tablet formulation is used and tablets (1 tablet = 270)
mg).
Compounding amount (mg)
30 mg of thiamine nitrate
Chondroitin sulfate sodium 500mg
Glucosamine hydrochloride 500mg
D-α-Tocopherol acetate 12mg
Hydroxypropylcellulose 73.6mg
Crystalline cellulose 700mg
Mannitol 600mg
Fragrance 2.4mg
Magnesium stearate 12mg
Total 2430mg

Example 6 (formulation containing vitamin B1 and hyaluronic acid)
According to the Japanese Pharmacopoeia, General Rules for Tablets “Tablets”, the following tablet prescription is used and tablets (1 tablet = 500
mg).
Compounding amount (mg)
Thiamine hydrochloride 24mg
Hyaluronic acid 450mg
Glucosamine hydrochloride 900mg
Hydroxypropylcellulose 90mg
Crystalline cellulose 519mg
Lactose 1002mg
Magnesium stearate 15mg
Total 2995mg

Example 7
According to the Japanese Pharmacopoeia, General Rules for Tablets “Tablets”, the following tablet formulation is used and tablets (1 tablet = 350
mg).
Compounding amount (mg)
Thiamine nitrate 2mg
Sodium chondroitin sulfate 400mg
Glucosamine sulfate 200mg
Hydroxypropylcellulose 42mg
Mannitol 1446mg
Magnesium stearate 10mg
Total 2100mg

Test example 1
For the preparations of test tablets 1 and 2 and Examples 8 and 9 shown in Table 1, due to deformation of the knee joint,
The effect of improving joint pain was examined for 10 persons with knee joint pain in daily life. In addition, the test tablet was prepared according to the formulation of Example 1 except changing the usage-amount of an active ingredient.

The test was performed by taking the test tablet 3 times a day for 3 weeks under the condition of 3 tablets each time and comparing it with the joint pain before taking. The evaluation was performed by scoring the degree of joint pain when walking, climbing stairs, standing up from a chair, and sitting upright. The degree of joint pain was scored according to the following criteria.

[Pain when walking]
Not painful: 0 points, painful when walking long distance: 1 point, painful even if walking short distance: 2 points [pain when going up and down stairs]
Can climb up and down easily: 0 points, can easily climb up and down with handrails: 1 point, step up and down step by step: 2 points [pain when getting up from a chair]
Not painful: 0 points, painful if not supported by hand: 1 point, painful if held by hand: 2 points [pain when sitting upright]
Can sit straight: 0 points, cannot sit down but can sit sideways: 1 point, can not sit sideways: 2 points For each item, the effect was evaluated by the difference of the total score of 10 people before and after taking. That is, the larger the difference Δ between the total points, the higher the improvement effect. The results are shown in Table 2.

Furthermore, the degree of joint pain in daily life was evaluated by VAS (Visual Analogue Scale). That is, as an evaluation method, the left end of the 10 cm scale is “no pain at all”.
When the score is 0 and the right edge is 100 points of “the best pain you can imagine”, ask the subject to indicate the degree of pain perceived at one point on the scale. I investigated. 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 VAS and the degree of joint pain during walking, stair climbing, standing up from a chair, sitting upright, and daily activities of the four items, Compared to a preparation containing sodium chondroitin sulfate and glucosamine hydrochloride, the preparation of the present invention further containing vitamin B1 improved the joint pain in any of the items, and a high effect was recognized. Moreover, it was shown that the limitation of the range of motion of the joint was eased from the improvement of the joint pain during the daily life movement, and the present invention was able to further relax the limitation of the range of motion of the joint.

Furthermore, even if it compared with the formulation which mix | blended vitamin B1 and chondroitin sodium sulfate, the formulation of this invention which further mix | blended glucosamine recognized the high effect.

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

Claims (1)

A composition containing vitamin B1 and glucosamine, the composition for treating or preventing joint pain comprising 0.1 to 1000 parts by weight of glucosamine with respect to 1 part by weight of vitamin B1.