JPS62201825A - Remedy for osteopathy - Google Patents
Remedy for osteopathyInfo
- Publication number
- JPS62201825A JPS62201825A JP61043632A JP4363286A JPS62201825A JP S62201825 A JPS62201825 A JP S62201825A JP 61043632 A JP61043632 A JP 61043632A JP 4363286 A JP4363286 A JP 4363286A JP S62201825 A JPS62201825 A JP S62201825A
- Authority
- JP
- Japan
- Prior art keywords
- bone
- remedy
- calcification
- insulin
- osteopathy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- ROPDWRCJTIRLTR-UHFFFAOYSA-L calcium metaphosphate Chemical compound [Ca+2].[O-]P(=O)=O.[O-]P(=O)=O ROPDWRCJTIRLTR-UHFFFAOYSA-L 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 229910052589 chlorapatite Inorganic materials 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 239000000788 chromium alloy Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- MYRTYDVEIRVNKP-UHFFFAOYSA-N divinylbenzene Substances C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052587 fluorapatite Inorganic materials 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229940095529 heparin calcium Drugs 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 108010066090 neutral insulin Proteins 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012766 organic filler Substances 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 229920001225 polyester resin Polymers 0.000 description 1
- 239000004645 polyester resin Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003505 polymerization initiator Substances 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 description 1
- 229910052573 porcelain Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001256 stainless steel alloy Inorganic materials 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000000332 tooth crown Anatomy 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 150000003704 vitamin D3 derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Dental Preparations (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、骨疾患、例えば前孔症、ベーチェット病、リ
ュウマチ関節炎、骨折、骨移植、歯周病等の治療に用い
られる桑剤に関するものであり、特に骨の石灰化作用を
促進させ、骨の強度向上及び修復作用を有する温血動物
用の骨疾患治療剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a mulberry agent used for the treatment of bone diseases, such as proforamia, Behcet's disease, rheumatoid arthritis, bone fractures, bone transplants, periodontal disease, etc. In particular, the present invention relates to a therapeutic agent for bone diseases for warm-blooded animals that promotes bone calcification, improves bone strength, and has repair effects.
これまでに、骨疾患の治療に関して種々の検討が行なわ
れている。例えば、同化ステロイド、エストロゲン、ポ
リリン酸塩、活性型ビタミンＤ３誘導体、プロスタグラ
シン類、バラサイロイドホルモン（Ｐ Ｔ Ｈ）、フッ
化物、カルントニン、芳香族カルボン酸類などである。Up to now, various studies have been conducted regarding the treatment of bone diseases. Examples include anabolic steroids, estrogens, polyphosphates, active vitamin D3 derivatives, prostaglasins, barathyroid hormone (P T H), fluoride, cartonin, aromatic carboxylic acids, and the like.
しかしながら、同化ステロイド、エストロゲンは副作用
が強＜、ホＩＪ ＩＪン酸塩は副作用が強い上に、骨吸
収抑制作用しか示さないという欠点がある。又、活性型
ビタミンＤ ３ Ｊ導体、プロスタグラシン類、パラサ
イロイドホルモンは、局所的には骨吸収作用を示し、石
灰化と相反する作用を有しており、使用がむずかしい。However, anabolic steroids and estrogens have strong side effects, and IJ salts have strong side effects and have the disadvantage of only exhibiting a bone resorption inhibitory effect. In addition, active vitamin D 3 J conductors, prostaglasins, and parathyroid hormones locally exhibit bone resorption action, which has an action contrary to calcification, making them difficult to use.
フッ化物及びカルシトニンは、骨吸収抑制作用のみを有
し、芳香族カルボン酸類は、骨吸収抑制作用と石灰化作
用とを有するが、石灰化作用が低いという欠点がある。Fluoride and calcitonin only have an effect of inhibiting bone resorption, and aromatic carboxylic acids have an effect of inhibiting bone resorption and a calcification effect, but they have the disadvantage of having a low calcification effect.
一方、骨吸収抑制作用や石灰化作用を有する物質とは異
なり、アルミナ、ハイドロキシアパタイト、第三リン酸
カルシウム、シリカ、カーボン、合金等の不溶性の物質
を骨の機械的補強材として用いることも行なわれている
が、これらは生体適合性が低く骨疾患治療効果は十分と
はいえなかった。On the other hand, unlike substances that have bone resorption inhibitory or calcifying effects, insoluble substances such as alumina, hydroxyapatite, tricalcium phosphate, silica, carbon, and alloys have also been used as mechanical reinforcement materials for bones. However, these have low biocompatibility and are not sufficiently effective in treating bone diseases.
従って、本発明は、安定性が高く副作用がないとともに
生体適合性にすぐれ、かつ骨吸収抑制作用とすぐれた石
灰化作用とを有する温血動物用の骨疾患治療剤を提供す
ることを目的とする。Therefore, an object of the present invention is to provide a therapeutic agent for bone diseases for warm-blooded animals that is highly stable, has no side effects, has excellent biocompatibility, and has bone resorption inhibitory and calcifying effects. do.
本発明は、石灰化促進作用を有する特定の物質と特定の
骨補填材とを併用すると、骨補填材により機械的強度の
向上と空間的スペースの確保が図られるうえに石灰化促
進剤により骨形成が促進されることによってそれぞれ単
独では得られないようなすぐれた骨疾患治療効果を得る
ことができ、上記問題点を有効に解決できるとの知見に
基づいてなされたのである。The present invention shows that when a specific substance that has a calcification promoting effect is used in combination with a specific bone grafting material, the bone grafting material improves mechanical strength and secures spatial space, and the mineralization accelerating agent improves bone grafting. This was done based on the knowledge that by promoting the formation of these drugs, it is possible to obtain excellent therapeutic effects for bone diseases that cannot be obtained by each method alone, and that the above-mentioned problems can be effectively solved.
すなわち、本発明は、囚インシュリン、プロタミン、為
コンドロイチン硫酸、ヘパリン、ヒアルロン酸、デキス
トラン硫酸、これらの塩及びビタミンにの群から選ばれ
る少なくとも１種の有効成分とｅ）水不溶性で常温で固
体の骨補填材とを含をすることを特徴とする骨疾患治療
剤を提供する。That is, the present invention provides at least one active ingredient selected from the group consisting of insulin, protamine, chondroitin sulfate, heparin, hyaluronic acid, dextran sulfate, salts thereof, and vitamins, and e) a water-insoluble and solid at room temperature. Provided is a therapeutic agent for bone diseases characterized by containing a bone filling material.
本発明で用いる成分図は石灰化促進作用を有するもので
ある。成分図のうち、インシュリン及びその製剤として
はインシュリン、インシュリン亜鉛水性懸濁液、イソフ
ェンインシュリン水性懸濁液、結晶性インシュリン亜鉛
水性懸濁液、二相性インシュリン水性懸濁液、ブタ精製
中性インシュリン、プロタミンインシュリン亜鉛水性懸
濁液、無品性インシュリン亜鉛水性懸濁液等であり、特
に好ましくは、プロタミンインシュリン亜鉛水性懸濁液
をあげることができる。又、本発明において用いられる
プロタミン及びその塩としては、プロタミン及びその塩
酸塩、硫酸塩等である。The composition diagram used in the present invention has a calcification promoting effect. In the composition diagram, insulin and its preparations include insulin, insulin zinc aqueous suspension, isophene insulin aqueous suspension, crystalline insulin zinc aqueous suspension, biphasic insulin aqueous suspension, and purified porcine neutral insulin. , protamine-insulin-zinc aqueous suspension, non-grade insulin-zinc aqueous suspension, etc. Particularly preferred is protamine-insulin-zinc aqueous suspension. In addition, protamine and its salts used in the present invention include protamine, its hydrochloride, sulfate, and the like.
本発明に用いられるコンドロイチン硫酸及びその塩とし
ては、コンドロイチン硫酸Ａ、コンドロイチン硫酸Ｂ１
コンドロイチン硫酸Ｃ及びコンドロイチンポリ硫酸とそ
れらのナトリウム塩、カルシウム塩等があげられる。ヘ
パリン及びその塩としては、ヘパリン、ヘパリンナトリ
ウム、ヘパリンナトリウム注射液、ヘパリンカルシウム
等である。ヒアルロン酸及びその塩としては、ヒアルロ
ン酸及びそのす） ＩＪウム塩、カルシウム塩があげら
れる。Chondroitin sulfate and its salts used in the present invention include chondroitin sulfate A, chondroitin sulfate B1
Examples include chondroitin sulfate C, chondroitin polysulfate, and their sodium salts and calcium salts. Examples of heparin and its salts include heparin, heparin sodium, heparin sodium injection, heparin calcium, and the like. Examples of hyaluronic acid and its salts include hyaluronic acid and its salts, and calcium salts.
デキストラン硫酸及びその塩としては、分子量５００か
ら５０． ＯＯＯのデキストランの部分的硫酸エステル
（硫黄台ｆｆ１１〜３０％）及びそのナトリウム塩、カ
ルシウム塩等があげられる。Dextran sulfate and its salts have a molecular weight of 500 to 50. Partial sulfate esters of OOO dextran (sulfur level ff 11 to 30%) and their sodium salts, calcium salts, etc. can be mentioned.
ビタミンにとしてはビタミンＫ ｌ 、ビタミンに２
及びビタミンに３ が例示される。Vitamin Kl, vitamin 2
and 3 are exemplified by vitamins.
本発明では上記囚成分の１種又は２種以上の混合物を使
用する。この際、上記（Ａ）成分のうち、特にコンドロ
イチン硫酸塩を用いるのが好ましい。In the present invention, one type or a mixture of two or more of the above-mentioned prison components is used. At this time, it is particularly preferable to use chondroitin sulfate among the components (A).
本発明において、ｅ）成分として用いる骨補填材として
は、上記の各骨補填材であって、水不溶性（例えば２０
℃における水への溶解度が０．０５％以下）で常温（５
０℃以下で）で固体の化合物であり、具体的には、次の
ものが例示される。アルミナ、水酸化アルミニウムなど
のアルミニウム系骨補填材、ハイドロキシアパタイト、
フッ素アパタイト、塩素アパタイト、カルシウムアパタ
イト、α型第三リン酸カルシウム、β型第三リン酸カル
シウム、メタリン酸カルシウム等のリン酸カルシウム系
骨補填材、二酸化ケイ素、磁器、ガラス等のシリカ系骨
補填材、カーボン、ポリスチレン、ポリエチレン、ポリ
プロピレン等の有機系補填材、コバルト−クロム合金、
ニッケルーコバルト合金、金、銀、プラチナ、ステンレ
ス、チタニウム合金等の金属系骨補填材があげられる。In the present invention, the bone grafting material used as component e) is each of the above-mentioned bone grafting materials, and is water-insoluble (for example, 20
Solubility in water at ℃ is 0.05% or less) at room temperature (5 ℃)
It is a compound that is solid at temperatures below 0°C), and specifically, the following are exemplified. Aluminum-based bone grafting materials such as alumina and aluminum hydroxide, hydroxyapatite,
Calcium phosphate bone grafting materials such as fluoroapatite, chlorapatite, calcium apatite, α-type tribasic calcium phosphate, β-type tribasic calcium phosphate, and calcium metaphosphate, silica-based bone grafting materials such as silicon dioxide, porcelain, and glass, carbon, polystyrene, and polyethylene. , organic fillers such as polypropylene, cobalt-chromium alloys,
Examples include metal bone grafting materials such as nickel-cobalt alloy, gold, silver, platinum, stainless steel, and titanium alloy.
本発明では、上記（Ｂ）成分の１種又は２種以上の混合
物を使用する。この際、上記（Ｂ）成分のうち、特にハ
イドロキシアパタイトなどのリン酸カルシウム系骨補填
材を用いるのが好ましい。又、成分（Ｂ）の形態は粉状
、粒状等いずれでもよい。In the present invention, one type or a mixture of two or more of the above-mentioned component (B) is used. At this time, it is particularly preferable to use a calcium phosphate bone grafting material such as hydroxyapatite among the components (B). Moreover, the form of component (B) may be either powdery or granular.
本発明の骨疾患治療剤は、疾患部位への外科的手術によ
る充填投与の方法により用いるのが好ましく、特に歯周
部位の骨疾患治療に有用である。The therapeutic agent for bone diseases of the present invention is preferably used by a method of surgically filling the diseased site, and is particularly useful for treating periodontal bone diseases.
投与量としては、体重１ ｋｇ当り、インシュリンでは
０．０１〜２０単位くＵ）、好ましくは０．１〜１単位
（Ｕ）であり、プロタミンでは０．００１〜１００ｍｇ
、好ましくは０．１〜２０ｍｇである。コンドロイチン
硫酸、ヘパリン、ヒアルロン酸、テストラン硫酸では０
．０１〜１０００ｍｇ、好ましくは１〜２００ｍｇであ
る。なお、これらの塩については、Ｊ離の形でその投与
量が上記の範囲となるようにするのがよい。ビタミンに
では０．００１〜１００ｍｇ、好ましくは０．１〜２０
ｍｇである。The dosage is 0.01 to 20 units (U) per kg of body weight for insulin, preferably 0.1 to 1 unit (U), and 0.001 to 100 mg for protamine.
, preferably 0.1 to 20 mg. 0 for chondroitin sulfate, heparin, hyaluronic acid, and Testolan sulfate
．． 01 to 1000 mg, preferably 1 to 200 mg. In addition, it is preferable that these salts be administered in the form of J-isolates so that the dosage falls within the above-mentioned range. For vitamins 0.001 to 100 mg, preferably 0.1 to 20
mg.
本発明に用いられる骨補填材の投与量は特に限定はない
が、通常体重１ ｋｇ当り１ｍｇ〜１０ｇ用いられる。The dosage of the bone grafting material used in the present invention is not particularly limited, but is usually 1 mg to 10 g per 1 kg of body weight.
本発明の骨疾患治療剤は、成分（Ｂ）の骨補填材に成分
囚を水溶液または無毒性溶媒希釈液の形で含浸させるか
、成分（Ｂ）と成分（Ａ）とを粉末状で混合するか、成
分（Ｂ）の表面に成分（〜を付着させるかのいずれかの
方法を採ることができる。成分（Ａ）と成分（Ｂ）の使
用比率囚／（Ｂ）は１／１０，０００，０００〜１／ｌ
であり、好ましくはｌ／１０［）、０００〜１／１００
（重量比〉である。The therapeutic agent for bone diseases of the present invention is prepared by impregnating the bone grafting material of component (B) with the component in the form of an aqueous solution or a diluted solution in a non-toxic solvent, or by mixing component (B) and component (A) in powder form. Alternatively, the component (~) can be attached to the surface of component (B).The usage ratio of component (A) and component (B)/(B) is 1/10, 000,000~1/l
and preferably l/10 [), 000 to 1/100
(weight ratio).
本発明の骨疾患治療剤には、さらに製剤化（安定化）の
ためにグリセリン、ソルビトール、プロピレングリコー
ル、ポリエチレングリコール、デキストラン、メチルセ
ルロース、ヒドロキシエチルセルロース、カルボキシメ
チルセルロース、ゼラチン、アルギン酸塩、トラガント
、ペクチン、アラビアゴム、可溶性デンプン等を添加す
ることができる。The therapeutic agent for bone diseases of the present invention further includes glycerin, sorbitol, propylene glycol, polyethylene glycol, dextran, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, gelatin, alginate, tragacanth, pectin, arabic acid, etc. for formulation (stabilization). Rubbers, soluble starches, etc. can be added.
本発明で用いる成分囚及び（Ｂ）は安全性の高いもので
ある。Ingredients and (B) used in the present invention are highly safe.
表−１に安全性のデータに示す。Table 1 shows the safety data.
本発明の骨疾患治療剤によれば、骨補填材により、骨疾
患部の空間的スペースが確保され、骨形成を司る骨芽細
胞が骨欠損表面に配列し易くなり、同時に用いられる石
灰化促進剤により骨芽細胞が活性化され骨基質の形成及
び骨の石灰化が促進されて、骨の強度向上及び修復作用
が行なわれるので、管孔症、ベーチェット病、リューマ
チ関節炎、骨折、骨移植、歯周病等の骨疾患に対してす
ぐれた効果を発揮するものである。このうちでも歯槽膿
漏や抜歯により減少した歯槽骨の補修（人工歯槽骨）や
歯牙の代替（人工歯根、人工歯冠等）を要する様な骨の
再形成の望めない歯周病に対しては、特に効果的である
。According to the therapeutic agent for bone diseases of the present invention, the bone substitute material secures a spatial space in the bone disease area, facilitates the arrangement of osteoblasts in charge of bone formation on the surface of the bone defect, and promotes mineralization that is used at the same time. The agent activates osteoblasts, promotes bone matrix formation and bone mineralization, improves bone strength and performs repair actions, so it can be used to treat canal disease, Behcet's disease, rheumatoid arthritis, bone fractures, bone grafts, etc. It exhibits excellent effects on bone diseases such as periodontal disease. Among these, for periodontal diseases in which bone regeneration cannot be expected, such as those that require repair of alveolar bone reduced due to alveolar pyorrhea or tooth extraction (artificial alveolar bone) or tooth replacement (artificial tooth root, artificial tooth crown, etc.) is particularly effective.
次に実施例により本発明を具体的に説明するが、本発明
はこれらに限定されるものではない。EXAMPLES Next, the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto.
実施例１
酸化アルミニウム（半井化学薬品■製・細胞磨砕用）２
０ｍｇと牛インシュリン（Ｓｉｇｍａ社製ｌ−５５００
）水溶液（１単位／ｍｉり０．１−をよく混合して、本
発明の骨疾患治療剤を調製した。次に体重２００ｇのラ
ット１０匹の左右大腿骨の中心部にそれぞれ直径ｌ ｍ
ｍの穴をドリルであけ、片足側の穴に上記治療剤２０ｍ
ｇを埋め込んだ。もう一方の足側の穴に酸化アルミニウ
ムのみ２０ｍｇを埋め込んだ。これらのラットを１週間
飼育後と殺し、欠損部を含む大腿骨の横断片をとり出し
アルコールで脱水処理後、スチレンモノマーで透徹し、
ポリエステルレジンを十分に含浸させて、重合開始剤を
加えて重合させ、埋込み部分を固定した。Example 1 Aluminum oxide (manufactured by Hani Chemical Co., Ltd., for cell grinding) 2
0mg and bovine insulin (Sigma l-5500)
) aqueous solution (1 unit/mm) was thoroughly mixed to prepare the bone disease therapeutic agent of the present invention.Next, a diameter of 1 m was placed at the center of the left and right femurs of 10 rats weighing 200 g.
Drill a hole with a diameter of m, and add 20m of the above therapeutic agent into the hole on one leg side.
embedded g. 20 mg of aluminum oxide alone was embedded in the hole on the other leg side. After raising these rats for one week, they were sacrificed, and the lateral fragment of the femur including the defect was removed, dehydrated with alcohol, and then transparentized with styrene monomer.
After sufficiently impregnating the polyester resin, a polymerization initiator was added and polymerized to fix the embedded portion.
これから欠損部を含む厚さ約６０μｍの横断研磨片を作
製し、マイクロラジオグラフを撮影した。A cross-sectional polished piece with a thickness of approximately 60 μm including the defect portion was prepared from this, and a microradiograph was taken.
判定は同一ラットごとに、マイクロラジオグラフで骨形
成度合を比較した。その結果を次に示す。Judgment was made by comparing the degree of bone formation in each rat using a microradiograph. The results are shown below.
結 果
同 等 ２
この結果から、本発明によれば骨形成が効果的に行なわ
れていることがわかる。Same result 2
This result shows that bone formation is effectively performed according to the present invention.
実施例２
コンドロイチン硫酸Ａナトリウム（生化学工業＠製）を
カチオン交換樹脂で酸型とし、水酸化カルシウムでカル
シウム塩（ｐＨ６，５〜７．０ ’）、としたものの乾
燥品２ｍｇを第三リン酸カルシウム（純正化学（４８３
製）１０ｍｇとよく混合して骨疾患治療剤を調製した。Example 2 2 mg of a dry product of sodium chondroitin sulfate A (manufactured by Seikagaku Kogyo@) made into an acid form with a cation exchange resin and made into a calcium salt (pH 6.5 to 7.0') with calcium hydroxide was added to tribasic calcium phosphate. (Junsei Chemical (483
A therapeutic agent for bone diseases was prepared by mixing well with 10 mg of the following products.
又、比較用に第三リン酸カルシウムを用いたほかは、実
施例１と同様にして骨形成効果を調べた。結果を次に示
す。In addition, the osteogenic effect was investigated in the same manner as in Example 1, except that tricalcium phosphate was used for comparison. The results are shown below.
結 果
同 等 １実
施例３
二酸化ケイ、累（関東化学＠裂、ＪＩＳ特級）１５ｍｇ
と硫酸ブロタミ７ （Ｓｉｇｍａ社製、Ｐ−４０２０）
ｉｎ＋ｇをよく混合して骨疾患治療剤を調製した。Results are the same 1 Example 3 Silicon dioxide, 15mg (Kanto Kagaku@Cabi, JIS special grade)
and Brotami sulfate 7 (manufactured by Sigma, P-4020)
A therapeutic agent for bone diseases was prepared by thoroughly mixing in+g.
又、比較のために二酸化ケイ素を用いたほかは、実施例
１と同様にして骨形成効果を調べた。結果を次に示す。In addition, the osteogenic effect was investigated in the same manner as in Example 1, except that silicon dioxide was used for comparison. The results are shown below.
同 等
に酸化ケイ累投与部
の方が骨形成蚤が多い １
実施例４
ポリスチレン−２％ジビニルベンゼンコポリマービーズ
（関東化学■製）１ｍｇとビタミンに２製剤ケーツー■
（エーザイ製、１０ｍｇ／ｍ）０．１ｍｌをよく混合
して骨疾患治療剤を調製した。Equivalent
There are more bone-forming fleas in areas where silicon oxide is repeatedly administered. 1 Example 4 1 mg of polystyrene-2% divinylbenzene copolymer beads (manufactured by Kanto Kagaku ■) and 2 preparations of vitamins K-2 ■
(manufactured by Eisai, 10 mg/m) were mixed well to prepare a therapeutic agent for bone diseases.
又、比較のためにポリスチレンジビニルベンゼンコボリ
マービーズを用いたほかは実施例１と同様にして骨形成
効果を調べた。結果を次に示す。In addition, the osteogenic effect was investigated in the same manner as in Example 1, except that polystyrene divinylbenzene copolymer beads were used for comparison. The results are shown below.
結 果result
Claims (2)
ン硫酸、ヘパリン、ヒアルロン酸、デキストラン硫酸、
これらの塩及びビタミンＫの群から選ばれる少なくとも
１種の有効成分と（Ｂ）水不溶性で常温で固体の骨補填
材とを含有することを特徴とする骨疾患治療剤。(1) (A) Insulin, protamine, chondroitin sulfate, heparin, hyaluronic acid, dextran sulfate,
A therapeutic agent for bone diseases characterized by containing at least one active ingredient selected from the group of these salts and vitamin K, and (B) a water-insoluble bone grafting material that is solid at room temperature.
記載の治療剤。(2) The therapeutic agent according to claim (1), which targets oral diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61043632A JP2604135B2 (en) | 1986-02-28 | 1986-02-28 | Oral bone disease treatment |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61043632A JP2604135B2 (en) | 1986-02-28 | 1986-02-28 | Oral bone disease treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62201825A true JPS62201825A (en) | 1987-09-05 |
| JP2604135B2 JP2604135B2 (en) | 1997-04-30 |
Family
ID=12669235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61043632A Expired - Lifetime JP2604135B2 (en) | 1986-02-28 | 1986-02-28 | Oral bone disease treatment |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2604135B2 (en) |
Cited By (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63179823A (en) * | 1987-01-19 | 1988-07-23 | Sunstar Inc | Composition for oral cavity |
| JPH03501415A (en) * | 1987-11-24 | 1991-03-28 | ピーピージー・インダストリーズ・インコーポレイテッド | organic photochromic pigments |
| GR890100526A (en) * | 1989-08-25 | 1991-12-30 | Bukh Meditec | Method for dental disease treatment |
| GB2224727B (en) * | 1988-09-29 | 1992-01-22 | Sangi Kk | Antimicrobial hydroxyapatite powders |
| WO1992012714A3 (en) * | 1991-01-23 | 1992-10-15 | Kuil R A Holding | Food supplement |
| US5240710A (en) * | 1988-02-26 | 1993-08-31 | Niels Bukh | Method of treating conditions of teeth and their supporting tissue with sucralfate |
| WO1996024362A1 (en) * | 1995-02-07 | 1996-08-15 | Shiseido Company, Ltd. | Antiinflammatory agents |
| US5639738A (en) * | 1992-02-20 | 1997-06-17 | Hyal Pharmaceutical Corporation | Treatment of basal cell carcinoma and actinic keratosis employing hyaluronic acid and NSAIDs |
| US5646129A (en) * | 1992-04-17 | 1997-07-08 | Fidia S.P.A. | Method of using low molecular weight hyaluronic acid for stimulating bone formation |
| US5674857A (en) * | 1992-02-20 | 1997-10-07 | Hyal Pharmaceutical Corporation | Use of hyaluronic acid to repair ischemia reperfusion damage |
| US5811410A (en) * | 1989-09-21 | 1998-09-22 | Hyal Pharmaceutical Corporation | Method of administering of a hyaluronic acid and an NSAID to decrease side effects of the NSAID |
| US5817644A (en) * | 1991-07-03 | 1998-10-06 | Hyal Pharmaceutical Corporation | Targeting of dosages of medicine and therapeutic agents |
| EP0839459A4 (en) * | 1995-05-28 | 1998-12-02 | Nishimura Masahiko | EASILY ABSORBABLE CALCIUM-CONTAINING COMPOSITION AND PROCESS FOR PRODUCING THE SAME |
| US5942498A (en) * | 1992-02-20 | 1999-08-24 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
| US5990095A (en) * | 1991-07-03 | 1999-11-23 | Hyal Pharmaceutical Corporation | Use of hyaluronic acid and forms to prevent arterial restenosis |
| US5990096A (en) * | 1990-09-18 | 1999-11-23 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
| WO2000024416A1 (en) * | 1998-10-28 | 2000-05-04 | Snow Brand Milk Products Co., Ltd. | Remedies for bone metabolic errors |
| US6103704A (en) * | 1991-07-03 | 2000-08-15 | Hyal Pharmaceutical Corporation | Therapeutic methods using hyaluronic acid |
| EP1021177A4 (en) * | 1997-02-04 | 2002-05-15 | John V Kosbab | Compositions and methods for prevention and treatment of vascular degenerative diseases |
| JP2005537832A (en) * | 2002-06-20 | 2005-12-15 | ドクサ アクティボラグ | Teeth filling material or implant material system and method for achieving powder material, hydration water, implant material and bonding |
| US7276344B2 (en) | 1995-02-20 | 2007-10-02 | Sankyo Co., Ltd. | Methods for using the osteoclastogenesis inhibitory factor (OCIF) protein |
| US8758819B2 (en) | 2006-09-13 | 2014-06-24 | Enhance Skin Products, Inc. | Cosmetic compositions for the treatment of skin and methods thereof |
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-
1986
- 1986-02-28 JP JP61043632A patent/JP2604135B2/en not_active Expired - Lifetime
Cited By (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63179823A (en) * | 1987-01-19 | 1988-07-23 | Sunstar Inc | Composition for oral cavity |
| JPH03501415A (en) * | 1987-11-24 | 1991-03-28 | ピーピージー・インダストリーズ・インコーポレイテッド | organic photochromic pigments |
| US5240710A (en) * | 1988-02-26 | 1993-08-31 | Niels Bukh | Method of treating conditions of teeth and their supporting tissue with sucralfate |
| GB2224727B (en) * | 1988-09-29 | 1992-01-22 | Sangi Kk | Antimicrobial hydroxyapatite powders |
| GB2236676B (en) * | 1988-09-29 | 1992-01-22 | Sangi Kk | Antimicrobial hydroxyapatite powders |
| GR890100526A (en) * | 1989-08-25 | 1991-12-30 | Bukh Meditec | Method for dental disease treatment |
| US5985851A (en) * | 1989-09-21 | 1999-11-16 | Hyal Pharmaceutical Corporation | Use of hyaluronic acid or its derivatives in peritoneal dialysis and formulations thereof |
| US5827834A (en) * | 1989-09-21 | 1998-10-27 | Hyal Pharmaceutical Corporation | Method of using hyaluronic acid or its pharmaceutically acceptable salts for the treatment of disease |
| US5914314A (en) * | 1989-09-21 | 1999-06-22 | Hyal Pharmaceutical Corporation | Use of a form of hyaluronic acid and a medicinal agent for reducing rejection of organs transplantation in mammals |
| US6069135A (en) * | 1989-09-21 | 2000-05-30 | Hyal Pharmaceutical Corporation | Use of hyaluronic acid or its derivatives to enhance delivery of therapeutic agents |
| US6048844A (en) * | 1989-09-21 | 2000-04-11 | Hyal Pharmaceutical Corporation | Treatment of conditions and disease |
| US5811410A (en) * | 1989-09-21 | 1998-09-22 | Hyal Pharmaceutical Corporation | Method of administering of a hyaluronic acid and an NSAID to decrease side effects of the NSAID |
| US5932560A (en) * | 1989-09-21 | 1999-08-03 | Hyal Pharmaceutical Corporation | Treatment of conditions and disease |
| US6194392B1 (en) | 1989-09-21 | 2001-02-27 | Hyal Pharmaceutical Corporation | Treatment of conditions and disease |
| US5830882A (en) * | 1989-09-21 | 1998-11-03 | Hyal Pharmaceutical Corporation | Compositions containing a form of hyaluronic acid and a medicinal agent for treating acne in mammals and methods for administration of such composition |
| US5929048A (en) * | 1989-09-21 | 1999-07-27 | Hyal Pharmaceutical Corporation | Treatment of conditions and disease |
| US5852002A (en) * | 1989-09-21 | 1998-12-22 | Hyal Pharmaceutical Corporation | Treatment of conditions and disease |
| US5985850A (en) * | 1989-09-21 | 1999-11-16 | Hyal Pharmaceuticals Corporation | Compositions comprising hyaluronic acid and drugs |
| US5990096A (en) * | 1990-09-18 | 1999-11-23 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
| WO1992012714A3 (en) * | 1991-01-23 | 1992-10-15 | Kuil R A Holding | Food supplement |
| US6103704A (en) * | 1991-07-03 | 2000-08-15 | Hyal Pharmaceutical Corporation | Therapeutic methods using hyaluronic acid |
| US5990095A (en) * | 1991-07-03 | 1999-11-23 | Hyal Pharmaceutical Corporation | Use of hyaluronic acid and forms to prevent arterial restenosis |
| US5817644A (en) * | 1991-07-03 | 1998-10-06 | Hyal Pharmaceutical Corporation | Targeting of dosages of medicine and therapeutic agents |
| US6147059A (en) * | 1992-02-20 | 2000-11-14 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
| US5914322A (en) * | 1992-02-20 | 1999-06-22 | Hyal Pharmaceutical Corporation | Treatment of disease and conditions |
| US5942498A (en) * | 1992-02-20 | 1999-08-24 | Hyal Pharmaceutical Corporation | Formulations containing hyaluronic acid |
| US5674857A (en) * | 1992-02-20 | 1997-10-07 | Hyal Pharmaceutical Corporation | Use of hyaluronic acid to repair ischemia reperfusion damage |
| US5639738A (en) * | 1992-02-20 | 1997-06-17 | Hyal Pharmaceutical Corporation | Treatment of basal cell carcinoma and actinic keratosis employing hyaluronic acid and NSAIDs |
| US5646129A (en) * | 1992-04-17 | 1997-07-08 | Fidia S.P.A. | Method of using low molecular weight hyaluronic acid for stimulating bone formation |
| US5872109A (en) * | 1995-02-07 | 1999-02-16 | Shiseido Company, Ltd. | Anti-inflammatory agent |
| WO1996024362A1 (en) * | 1995-02-07 | 1996-08-15 | Shiseido Company, Ltd. | Antiinflammatory agents |
| US7276344B2 (en) | 1995-02-20 | 2007-10-02 | Sankyo Co., Ltd. | Methods for using the osteoclastogenesis inhibitory factor (OCIF) protein |
| US7468268B2 (en) | 1995-02-20 | 2008-12-23 | Daiichi Sankyo Co., Ltd. | Nucleic acid molecules encoding osteoclastogenesis inhibitory factor proteins |
| EP0839459A4 (en) * | 1995-05-28 | 1998-12-02 | Nishimura Masahiko | EASILY ABSORBABLE CALCIUM-CONTAINING COMPOSITION AND PROCESS FOR PRODUCING THE SAME |
| EP1021177A4 (en) * | 1997-02-04 | 2002-05-15 | John V Kosbab | Compositions and methods for prevention and treatment of vascular degenerative diseases |
| WO2000024416A1 (en) * | 1998-10-28 | 2000-05-04 | Snow Brand Milk Products Co., Ltd. | Remedies for bone metabolic errors |
| AU755422B2 (en) * | 1998-10-28 | 2002-12-12 | Sankyo Company Limited | Remedies for bone metabolic errors |
| JP2005537832A (en) * | 2002-06-20 | 2005-12-15 | ドクサ アクティボラグ | Teeth filling material or implant material system and method for achieving powder material, hydration water, implant material and bonding |
| US7699925B2 (en) | 2002-06-20 | 2010-04-20 | Doxa Ab | System for a dental filling material or implant material, and powdered material, hydration liquid, implant material and method of achieving bonding |
| US8758819B2 (en) | 2006-09-13 | 2014-06-24 | Enhance Skin Products, Inc. | Cosmetic compositions for the treatment of skin and methods thereof |
| CN110339401A (en) * | 2019-07-11 | 2019-10-18 | 江西瑞济生物工程技术股份有限公司 | A kind of orthopaedics compound bio amnion preparation method |
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|---|---|
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