JPH0455737B2 - - Google Patents
Info
- Publication number
- JPH0455737B2 JPH0455737B2 JP62210713A JP21071387A JPH0455737B2 JP H0455737 B2 JPH0455737 B2 JP H0455737B2 JP 62210713 A JP62210713 A JP 62210713A JP 21071387 A JP21071387 A JP 21071387A JP H0455737 B2 JPH0455737 B2 JP H0455737B2
- Authority
- JP
- Japan
- Prior art keywords
- adsorbent
- mgo
- phosphorus
- tio
- composite
- 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.)
- Expired - Lifetime
Links
- 239000003463 adsorbent Substances 0.000 claims description 25
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 22
- 229910052698 phosphorus Inorganic materials 0.000 claims description 22
- 239000011574 phosphorus Substances 0.000 claims description 22
- 229910010413 TiO 2 Inorganic materials 0.000 claims description 19
- 239000002131 composite material Substances 0.000 claims description 16
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N titanium dioxide Inorganic materials O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 230000008081 blood perfusion Effects 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 21
- 239000000395 magnesium oxide Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 9
- 238000001179 sorption measurement Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Chemical compound [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 208000001647 Renal Insufficiency Diseases 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 201000005991 hyperphosphatemia Diseases 0.000 description 4
- 201000006370 kidney failure Diseases 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000004438 BET method Methods 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- -1 aluminum compound Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000001354 calcination Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- PPQREHKVAOVYBT-UHFFFAOYSA-H dialuminum;tricarbonate Chemical compound [Al+3].[Al+3].[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O PPQREHKVAOVYBT-UHFFFAOYSA-H 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000010304 firing Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 241000116710 Ferula foetidissima Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- LMYFRNPXRCFJPI-UHFFFAOYSA-J [Th+4].P(=O)(O)(O)[O-].P(=O)(O)(O)[O-].P(=O)(O)(O)[O-].P(=O)(O)(O)[O-] Chemical compound [Th+4].P(=O)(O)(O)[O-].P(=O)(O)(O)[O-].P(=O)(O)(O)[O-].P(=O)(O)(O)[O-] LMYFRNPXRCFJPI-UHFFFAOYSA-J 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940118662 aluminum carbonate Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 230000005977 kidney dysfunction Effects 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 150000002681 magnesium compounds Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 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
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003609 titanium compounds Chemical class 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- External Artificial Organs (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Description
［発明の技術分野］
本発明は、MgO−TiO2複合物よりなる吸着剤
及び該該吸着剤の抗高リン血症剤に係る。
［発明の技術的背景］
腎臓や肝臓に機能障害をもつ患者では、代謝老
廃物等の体外***能が不十分となり、これ等の物
質が体内に蓄積され、結果として種々の生理的障
害を生じている。従つて、これ等の機能障害者の
病態改善には、一般に代謝老廃物等を生体から取
り除くことが行なわれている。
例えば、腎機能障害者の典型として腎不全患者
が知られているが、この患者に対しては、現在、
透析膜を用いる血液浄化法或いは活性炭を用いる
血液潅流法等の治療法が施されている。
ところで腎不全患者では、尿中へのリン***機
能の低下に伴う高リン血症の併発が問題になつて
いるが、前記した従来の治療法では高リン血症の
病態を改善し得ないでいる。即ち、前者の透析膜
による血液浄化法は血中のリン濃度を十分に制御
し得るものではなく、しかも高リン血症の最大要
因であるリンの腸管吸収に対しては全く無力であ
る。一方、後者の活性炭を用いる治療法ではリン
等の無機物質に対する吸着力が非常に劣るという
活性炭自身の特性上の問題を有している。
このため、高リン血症に対する対症療法として
従来は、水酸化アルミニウムや炭酸アルミニウム
等のアルミニウム化合物系のリン結合剤の服用が
行なわれている。しかしながら、アルミニウム化
合物系のリン結合剤は、多量のリン摂取者（1500
mg／日）に対しては効果が少なく、また多量の服
用によつて便秘、悪心、嘔吐等の副作用の発現の
恐れがあり、さらに最近ではAl骨症やAl脳症を
惹起する等の報告もなされている。
［発明の目的］
本発明者等は、前記実情に鑑み、生体への安全
性が高くしかもリン吸着特性が経時的に非常に安
定している吸着剤の提供を目的として鋭意検討し
た結果、特定の組成で構成されるMgO−TiO2複
合物が極めて合目的であることを見い出し、本発
明の完成に至つた。
［発明の構成］
即ち、前記知見に基づ本発明は、下記特性を有
するMgO−TiO2複合物よりなる吸着剤（以下、
本発明の吸着剤と称する）及び該吸着剤の抗高リ
ン血症剤としての利用に係る。
組 成 比：MgO／TiO2（モル比）＝99.99／
0.01〜80／20
比表面積：50〜700m2／ｇ（BET法）
結晶構造：粉末Ｘ線回折法において、MgOの
結晶回折パターンを示す。
［発明の開示］
以下、本発明を詳述する。
本発明の吸着剤はマグネシウム化合物とチタン
化合物を混合し、加水分解して得られる沈澱物を
焼成することにより製造される。即ち、本発明の
吸着剤は、塩化マグネシウムと四塩化チタニウム
の如きそれぞれの塩を所与の割合で混合後、アン
モニア水等のアルカリで加水分解する不均一沈澱
法、前記アルカリの代りに尿素を用いる均一共沈
澱法、金属のアルコキシドを混合して加水分解す
る方法、あるいは金属の水酸化物等を混練する方
法、更には一方の金属塩の水溶液に他の金属酸化
物を浸漬させた後、さらにそれにアンモニア水を
加える方法等々によつて調製した沈澱物を、焼成
処理することで製造し得る。
焼成工程の目的は、MgOとTiO2を複合化する
と共に、吸着剤としての特性、例えば比表面積、
表面化学構造、例えば表面OH基等を調整するこ
とにある。焼成条件は、調製法、調整条件、配合
割合等によつて異なり特に限定されないが、通常
200℃〜1000℃、好ましくは300℃〜700℃、更に
好ましくは350℃〜500℃の温度が好適である。
なお、前記製法によつて得られる複合物におい
て、構成成分の１つであるTiO2の量が多くなる
に従つて結晶構造の乱れが大きくなり、MgO−
TiO2複合物はTiO2の比率が20％を越えるとMgO
結晶特有の粉末Ｘ線回折パターンが消滅し、同時
にリンの吸着性能が著しく低下する。
また、TiO2の比率が小さい場合には、酸化マ
グネシウム単独のものとＸ線回折的に区別がつき
難いものとなる。しかしながら、酸化マグネシウ
ム単独で構成されるものは大気中の炭酸ガスの影
響を受け経時的にリン吸着性能の低下がみられる
のに対し、本発明においては、TiO2の存在によ
つて、MgO−TiO2複合物は大気中においても長
時間安定な吸着性能を維持するという優れた特性
を発現する。
従つて本発明の吸着剤は、前記方法で製造され
るMgO−TiO2複合物において、MgO／TiO2（モ
ル比）＝99.99／0.01〜80／20、好ましくは99.9／
0.1〜90／10、比表面積50〜700m2／ｇ、好ましく
は100〜500m2／ｇ、粉末Ｘ線回折で、MgOの結
晶回折パターン、例えば2θ＝43.07゜、62.55゜を示
すことを特徴とするものである。
前記本発明の吸着剤はリン及びリン化合物の吸
着性に優れる。しかも、本発明の吸着剤は、JCl
−SDDラツトに5000mg／Kgを経口投与した場合、
急性毒性として何らの異常も示さない。従つて本
発明の吸着剤は単独で、あるいは、薬剤組成物の
形態で抗高リン血症剤として利用できる。前記抗
高リン血症剤としての使用に際し、本発明の吸着
剤は粉末状、顆粒状、球状等の形態で、あるい
は、それらと医薬上許容される担体及び／又は補
剤との組成物として種々の製剤形態が可能であ
る。
製剤形態を具例すれば、錠剤，舌下錠剤，丸
剤，散剤，顆粒剤，カプセル剤，坐剤，トロー
チ，あるいは水性もしくは油性溶剤，懸濁液剤，
乳剤，シロツプ剤、ゲル化剤等の各種形態であ
る。錠剤，散剤，カプセル剤等においては腸溶性
の剤形を包含し得るものである。
また医薬上許容される担体は特に限定されない
が、一般的に、水，ゼラチン，乳糖，でんぷん，
ペクチン，ステアリン酸マグネシウム，ステアリ
ン酸，タルク，植物油，アラビアゴム，ポリアル
キレングリコール，ワセリン，ソルビタントリオ
レート，ポリオキシエチレンソルビタンモノオレ
ート，アルキルフエノール，脂肪族アルコール，
ポリビニルピロリドン等を例示し得る。
また製剤化に際して、必要に応じ、甘味料，香
味料，着色剤，保存剤，浸透圧調整用塩，緩衝剤
等の通常の製薬補助剤を用いることも可能であ
る。
該組成物は経口，経腸的に服用出来る。
本発明の吸着剤の製剤組成物中における含有率
は適宜変化し得るが、１重量％〜99重量％、好ま
しくは10重量％〜99重量％を含有させることが出
来る。
服用量は、疾患の程度等によつても異なるが、
通常MgO−TiO2複合物として0.1〜２ｇ／回、１
日３回程度が適度である。また、緊急を要する場
合は勿論この限りではない。なお、腎不全患者に
適用する場合、その時期は透析前の保存期あるい
は透析期何れであつても良い。
本発明の吸着剤は、前記する経口剤としての使
用の他に、単独もしくはヘパリン等の生体適合性
物質等を被覆することで血液潅流用の吸着剤とし
て用いることができる。
以下、実施例をもつて本発明を詳述する。
実施例 １
撹拌した水中に0.57ｇのチタンテトライソプロ
ポキシド［（CH3）2CHO］4Tiを滴下した後、硝酸
（61wt％）、1.2ｇを加えた。次いでこの溶液に、
51.3ｇの硝酸マグネシウムMg（NO3）2・6H2Oを
水50mlに溶かした溶液を加えた後、28％アンモニ
ア水30ｇを徐々に加えて加水分解し、生成した沈
澱を遠心分離した。得られた沈澱を十分に水洗し
た後、窒素気流下、200℃／hrで400℃まで昇温
し、400℃で１時間保持し、7.0ｇのMgO／TiO2
（モル比99／１）の複合物を得た。
第１図にこのMgO−TiO2複合物の粉末Ｘ線回
折図を示す。
実施例 ２
撹拌した水中に5.7ｇのチタンテトライソプロ
ポキシド［（CH3）2CHO］4Tiを滴下した後、硝酸
（61wt％）12.4ｇを加えた。次いでこの溶液に、
46.2ｇの硝酸マグネシウムMg（NO3）2・6H2Oを
水50mlに溶かした溶液を加えた後、28％アンモニ
ア水29ｇを徐々に加えて加水分解し、生成した沈
澱を遠心分離した。得られた沈澱を十分水洗した
後、窒素気流下、200℃／hrで400℃まで昇温し、
400℃で１時間保持し7.3ｇのMgO／TiO2（モル比
90／10）の複合物を得た。
比較例 １
51.3ｇの硝酸マグネシウムMg（NO3）2・6H2O
を水50mlに撹拌しながら溶解した液に、28％アン
モニア水29ｇを徐々に加えて加水分解し、成した
沈澱を遠心分離した。得られた沈澱を十分水洗し
た後、窒素気流下200℃／hrで400℃まで昇温し、
400℃で１時間保持し、6.4ｇの酸化マグネシウム
を得た。第２図にこの生成物の粉末Ｘ線回折図を
示す。
実施例 ３
実施例１，２及び比較例１で得られた試料につ
いて、比表面積（BET法）、粉末Ｘ線回折を測定
した結果を第１表に示す。
[Technical Field of the Invention] The present invention relates to an adsorbent comprising a MgO-TiO 2 composite and an antihyperphosphatemic agent for the adsorbent. [Technical Background of the Invention] In patients with kidney or liver dysfunction, the ability to excrete metabolic waste products from the body is insufficient, and these substances accumulate in the body, resulting in various physiological disorders. ing. Therefore, in order to improve the pathological conditions of these functionally impaired individuals, metabolic waste products and the like are generally removed from the living body. For example, patients with renal failure are known to be typical of patients with renal dysfunction;
Treatment methods include blood purification using a dialysis membrane and blood perfusion using activated carbon. Incidentally, in patients with renal failure, hyperphosphatemia associated with a decline in the ability to excrete phosphorus into the urine is a problem, but the conventional treatments described above cannot improve the condition of hyperphosphatemia. There is. That is, the former blood purification method using a dialysis membrane cannot sufficiently control the phosphorus concentration in the blood, and is completely powerless against intestinal absorption of phosphorus, which is the most important factor in hyperphosphatemia. On the other hand, the latter treatment method using activated carbon has a problem due to the characteristics of activated carbon itself, that is, its adsorption power for inorganic substances such as phosphorus is extremely poor. For this reason, conventionally, as a symptomatic treatment for hyperphosphatemia, phosphorus binders based on aluminum compounds such as aluminum hydroxide and aluminum carbonate have been taken. However, aluminum compound-based phosphorus binders are not suitable for people who consume large amounts of phosphorus (1500
mg/day), and there is a risk of side effects such as constipation, nausea, and vomiting if taken in large doses.Moreover, there have been reports recently that it may cause Al osteopathy and Al encephalopathy. being done. [Purpose of the Invention] In view of the above-mentioned circumstances, the inventors of the present invention have conducted intensive studies with the aim of providing an adsorbent that is highly safe for living organisms and has extremely stable phosphorus adsorption properties over time. The inventors have discovered that a MgO-TiO 2 composite having the following composition is extremely suitable for this purpose, and have completed the present invention. [Structure of the Invention] That is, based on the above knowledge, the present invention provides an adsorbent (hereinafter referred to as
(referred to as the adsorbent of the present invention) and the use of the adsorbent as an antihyperphosphatemic agent. Composition ratio: MgO/TiO 2 (molar ratio) = 99.99/
0.01 to 80/20 Specific surface area: 50 to 700 m 2 /g (BET method) Crystal structure: Shows a crystal diffraction pattern of MgO in powder X-ray diffraction method. [Disclosure of the Invention] The present invention will be described in detail below. The adsorbent of the present invention is produced by mixing a magnesium compound and a titanium compound, and calcining the resulting precipitate by hydrolysis. That is, the adsorbent of the present invention is produced by a heterogeneous precipitation method in which salts such as magnesium chloride and titanium tetrachloride are mixed in a given ratio and then hydrolyzed with an alkali such as aqueous ammonia, or by using urea in place of the alkali. The homogeneous coprecipitation method used, the method of mixing and hydrolyzing metal alkoxides, the method of kneading metal hydroxides, etc., and the method of immersing the other metal oxide in an aqueous solution of one metal salt, It can be produced by firing a precipitate prepared by adding ammonia water thereto. The purpose of the calcination process is to combine MgO and TiO 2 and improve their adsorbent properties, such as specific surface area,
The goal is to adjust the surface chemical structure, such as surface OH groups. Firing conditions vary depending on the preparation method, adjustment conditions, blending ratio, etc., and are not particularly limited, but usually
Temperatures of 200°C to 1000°C, preferably 300°C to 700°C, more preferably 350°C to 500°C are suitable. In addition, in the composite obtained by the above manufacturing method, as the amount of TiO 2 , which is one of the constituent components, increases, the disorder of the crystal structure increases, and MgO-
TiO 2 composite becomes MgO when the ratio of TiO 2 exceeds 20%
The powder X-ray diffraction pattern unique to the crystal disappears, and at the same time, the phosphorus adsorption performance decreases significantly. Moreover, when the ratio of TiO 2 is small, it becomes difficult to distinguish from magnesium oxide alone in terms of X-ray diffraction. However, in contrast to those composed of magnesium oxide alone whose phosphorus adsorption performance deteriorates over time due to the influence of carbon dioxide in the atmosphere, in the present invention, due to the presence of TiO 2 , MgO− TiO 2 composite exhibits the excellent property of maintaining stable adsorption performance for a long time even in the atmosphere. Therefore, in the adsorbent of the present invention, in the MgO-TiO 2 composite produced by the above method, MgO/TiO 2 (molar ratio) = 99.99/0.01 to 80/20, preferably 99.9/
0.1 to 90/10, a specific surface area of 50 to 700 m 2 /g, preferably 100 to 500 m 2 /g, and a crystal diffraction pattern of MgO, for example, 2θ = 43.07°, 62.55°, in powder X-ray diffraction. It is something to do. The adsorbent of the present invention has excellent adsorption properties for phosphorus and phosphorus compounds. Moreover, the adsorbent of the present invention has JCl
- When administered orally to SDD rats at 5000 mg/Kg,
No abnormalities are shown in terms of acute toxicity. Therefore, the adsorbent of the present invention can be used alone or in the form of a pharmaceutical composition as an antihyperphosphatemic agent. When used as the antihyperphosphatemia agent, the adsorbent of the present invention may be in the form of powder, granules, spheres, etc., or as a composition of these with a pharmaceutically acceptable carrier and/or adjuvant. Various formulation forms are possible. Specific formulation forms include tablets, sublingual tablets, pills, powders, granules, capsules, suppositories, troches, aqueous or oily solvents, suspensions,
They come in various forms such as emulsions, syrups, and gelling agents. Tablets, powders, capsules, etc. may include enteric-coated dosage forms. Pharmaceutically acceptable carriers are not particularly limited, but generally include water, gelatin, lactose, starch,
Pectin, magnesium stearate, stearic acid, talc, vegetable oil, gum arabic, polyalkylene glycol, petrolatum, sorbitan triolate, polyoxyethylene sorbitan monooleate, alkyl phenol, aliphatic alcohol,
Examples include polyvinylpyrrolidone. Further, when preparing the formulation, it is also possible to use conventional pharmaceutical auxiliaries such as sweeteners, flavorants, coloring agents, preservatives, salts for adjusting osmotic pressure, and buffering agents, if necessary. The composition can be taken orally or enterally. Although the content of the adsorbent of the present invention in the pharmaceutical composition may vary as appropriate, it can be contained in the range of 1% to 99% by weight, preferably 10% to 99% by weight. The dosage varies depending on the severity of the disease, etc.
Usually 0.1 to 2 g/time as MgO-TiO 2 composite, 1
About 3 times a day is appropriate. Of course, this does not apply in cases of emergency. When applied to patients with renal failure, the period may be either the predialysis period or the dialysis period. The adsorbent of the present invention can be used as an adsorbent for blood perfusion, either alone or by coating with a biocompatible substance such as heparin, in addition to being used as an oral preparation as described above. Hereinafter, the present invention will be explained in detail with reference to Examples. Example 1 After dropping 0.57 g of titanium tetraisopropoxide [(CH 3 ) 2 CHO] 4 Ti into stirred water, 1.2 g of nitric acid (61 wt%) was added. Then to this solution,
After adding a solution of 51.3 g of magnesium nitrate Mg(NO 3 ) 2.6H 2 O dissolved in 50 ml of water, 30 g of 28% aqueous ammonia was gradually added for hydrolysis, and the resulting precipitate was centrifuged. After thoroughly washing the obtained precipitate with water, the temperature was raised to 400°C at a rate of 200°C/hr under a nitrogen stream, held at 400°C for 1 hour, and 7.0g of MgO/TiO 2
A composite with a molar ratio of 99/1 was obtained. FIG. 1 shows a powder X-ray diffraction pattern of this MgO-TiO 2 composite. Example 2 After dropping 5.7 g of titanium tetraisopropoxide [(CH 3 ) 2 CHO] 4 Ti into stirred water, 12.4 g of nitric acid (61 wt%) was added. Then to this solution,
After adding a solution of 46.2 g of magnesium nitrate Mg(NO 3 ) 2.6H 2 O dissolved in 50 ml of water, 29 g of 28% aqueous ammonia was gradually added for hydrolysis, and the resulting precipitate was centrifuged. After thoroughly washing the obtained precipitate with water, the temperature was raised to 400°C at 200°C/hr under a nitrogen stream.
7.3g of MgO/ TiO2 (molar ratio
A composite of 90/10) was obtained. Comparative example 1 51.3g of magnesium nitrate Mg (NO 3 ) 2・6H 2 O
was dissolved in 50 ml of water with stirring, and 29 g of 28% ammonia water was gradually added for hydrolysis, and the precipitate formed was centrifuged. After thoroughly washing the obtained precipitate with water, the temperature was raised to 400°C at 200°C/hr under a nitrogen stream.
The mixture was maintained at 400°C for 1 hour to obtain 6.4g of magnesium oxide. FIG. 2 shows the powder X-ray diffraction pattern of this product. Example 3 Table 1 shows the results of specific surface area (BET method) and powder X-ray diffraction measurements of the samples obtained in Examples 1 and 2 and Comparative Example 1.
【表】
実施例 ４
11週令のJcl−SDラツトの左腎動脈分枝を部分
結紮し、その７日後に右腎の腎門部を結紮して腎
不全モデルラツトを作製した。４匹のラツトを使
用して30日間の経過観察後尾静脈より採血し、血
清中のクレアチニン及び無機リン濃度がそれぞれ
1.7±0.3（mg／dl）、7.1±0.3（mg／dl）に上昇した
時点から、飼料（CE−２：日本クレア製）に実
施例１で得られた試料を0.1％混合した飼料を５
日間自由摂取させた。５日間の投与終了後、尾静
脈より採血し、血清中の無機リン濃度を測定し
た。結果を第２表に示す。
測定機器
クレアチニン：ベツクマンクレアチニン分析計
（ベツクマン社製）
無機リン：RaBA−Mark（京都第一科学
製）[Table] Example 4 The left renal artery branch of an 11-week-old Jcl-SD rat was partially ligated, and 7 days later, the renal hilum of the right kidney was ligated to create a renal failure model rat. After 30 days of follow-up observation using 4 rats, blood was collected from the tail vein, and serum creatinine and inorganic phosphorus concentrations were determined.
1.7 ± 0.3 (mg/dl) and 7.1 ± 0.3 (mg/dl), the feed (CE-2: manufactured by CLEA Japan) was mixed with 0.1% of the sample obtained in Example 1 for 5 minutes.
It was allowed to be taken ad libitum for days. After 5 days of administration, blood was collected from the tail vein and the inorganic phosphorus concentration in the serum was measured. The results are shown in Table 2. Measuring equipment Creatinine: Beckman creatinine analyzer (manufactured by Beckman) Inorganic phosphorus: RaBA-Mark (manufactured by Kyoto Daiichi Kagaku)
【表】
実施例 ５
実施例１，２及び比較例１で得られた試料を空
気中に放置した場合の経時的なリン吸着量の変化
を追跡した。その結果を第３図に示す。比較例１
で得られたMgO単独では、経時的にリン吸着性
能が低下するのに対し、実施例１及び２で得られ
たMgO−TiO2複合物では吸着量に変化は認めら
れず、安定に保ち得た。
なお、リン吸着量は、リン酸二水素トリウム
NaH2PO4濃度3.22mmole／ｌの溶液50mlを各々共
栓三角フラスコにとり、各試料100mgを加え、室
温で２時間振盪した後、過し、液中のリン濃
度をRaBAエース（京都第一科学製）により測定
し、リン吸着量を求めた。[Table] Example 5 When the samples obtained in Examples 1 and 2 and Comparative Example 1 were left in the air, changes in the amount of phosphorus adsorbed over time were tracked. The results are shown in FIG. Comparative example 1
With MgO obtained alone, the phosphorus adsorption performance deteriorates over time, whereas with the MgO-TiO 2 composites obtained in Examples 1 and 2, no change was observed in the adsorption amount and it could be kept stable. Ta. The amount of phosphorus adsorbed is thorium dihydrogen phosphate.
50 ml of a solution with a NaH 2 PO 4 concentration of 3.22 mmole/l was placed in a stoppered Erlenmeyer flask, 100 mg of each sample was added, and the mixture was shaken at room temperature for 2 hours, filtered, and the phosphorus concentration in the solution was measured using RaBA Ace (Kyoto Daiichi Scientific Co., Ltd.). The amount of phosphorus adsorption was determined by measuring the amount of phosphorus adsorbed by
第１図及び第２図はそれぞれ本発明MgO−
TiO2複合物及び比較物質のＸ線回折パターンを
示す図であり、第３図は本発明のMgO−TiO2複
合物と比較物質のリン吸着量の経時変化を示す図
である。
FIG. 1 and FIG. 2 respectively show the MgO-
FIG. 3 is a diagram showing X - ray diffraction patterns of a TiO 2 composite and a comparative material, and FIG. 3 is a diagram showing changes over time in the amount of phosphorus adsorbed in the MgO-TiO 2 composite of the present invention and a comparative material.
Claims (1)
るリン吸着剤。 ２ MgO−TiO2複合物のMgO／TiO2比がモル
比で99.99／0.01〜80／20である特許請求の範囲
第１項記載の吸着剤。 ３ MgO−TiO2複合物の比表面積が50〜700
m2／ｇである特許請求の範囲第１項記載の吸着
剤。 ４ 粉末Ｘ線回折法において、MgOの結晶回折
パターンを示す特許請求の範囲第１項記載の吸着
剤。 ５ 抗高リン血症剤である特許請求の範囲第１項
記載の吸着剤。 ６ 血液灌流用吸着剤である特許請求の範囲第１
項記載の吸着剤。[Claims] 1. A phosphorus adsorbent comprising a MgO-TiO 2 composite. 2. The adsorbent according to claim 1, wherein the MgO- TiO2 composite has a MgO/ TiO2 ratio of 99.99/0.01 to 80/20 in molar ratio. 3 Specific surface area of MgO- TiO2 composite is 50-700
The adsorbent according to claim 1, wherein the adsorbent has a particle size of m 2 /g. 4. The adsorbent according to claim 1, which exhibits a crystal diffraction pattern of MgO in powder X-ray diffraction. 5. The adsorbent according to claim 1, which is an antihyperphosphatemic agent. 6 Claim 1 which is an adsorbent for blood perfusion
Adsorbent as described in section.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62210713A JPS6456140A (en) | 1987-08-25 | 1987-08-25 | Compound adsorbent |
| ES88307827T ES2054816T3 (en) | 1987-08-25 | 1988-08-24 | COMPLEX OF MAGNESIUM OXIDE AND TITANIUM DIOXIDE AS A PHOSPHATE ADSORBENT. |
| DE8888307827T DE3881141T2 (en) | 1987-08-25 | 1988-08-24 | COMPOSITION OF MAGNESIUM OXYD AND TITANDIOXYD AS A PHOSPHATE SORBENT. |
| EP88307827A EP0311244B1 (en) | 1987-08-25 | 1988-08-24 | Complex of magnesium oxide and titanium dioxide as a phosphate adsorbent |
| US07/235,415 US4988569A (en) | 1987-08-25 | 1988-08-24 | Complex phosphate adsorbent of MgO-TiO2 |
| CA000575490A CA1324601C (en) | 1987-08-25 | 1988-08-24 | Complex phosphate adsorbent |
| KR1019880010842A KR910004018B1 (en) | 1987-08-25 | 1988-08-25 | Phosphate adsorbent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62210713A JPS6456140A (en) | 1987-08-25 | 1987-08-25 | Compound adsorbent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6456140A JPS6456140A (en) | 1989-03-03 |
| JPH0455737B2 true JPH0455737B2 (en) | 1992-09-04 |
Family
ID=16593869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62210713A Granted JPS6456140A (en) | 1987-08-25 | 1987-08-25 | Compound adsorbent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6456140A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04106020U (en) * | 1991-02-27 | 1992-09-11 | 栃木富士産業株式会社 | hub clutch |
| CN1313204C (en) * | 2004-10-13 | 2007-05-02 | 河南工业大学 | Process for preparing nanometer titania doping photocatalyst |
-
1987
- 1987-08-25 JP JP62210713A patent/JPS6456140A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6456140A (en) | 1989-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5968976A (en) | Pharmaceutical composition containing selected lanthanum carbonate hydrates | |
| EP0311244B1 (en) | Complex of magnesium oxide and titanium dioxide as a phosphate adsorbent | |
| CA1149743A (en) | Porous and spherical carbonaceous product | |
| US7588782B2 (en) | Rare earth metal compositions for treating hyperphosphatemia and related methods | |
| US3637657A (en) | Aluminum complex of sulfated polysaccharide and process for the preparation thereof | |
| US9511091B2 (en) | Rare earth metal compounds, methods of making, and methods of using the same | |
| JP2981573B2 (en) | Phosphate ion adsorbent | |
| KR20080037083A (en) | Pharmaceutical-grade ferric organic compounds, uses thereof and methods of making same | |
| JPH0455737B2 (en) | ||
| JPH0422618B2 (en) | ||
| CA2122908C (en) | Pharmaceutical compositions of gallium complexes of 3-hydroxy-4-pyrones | |
| EP2194028B1 (en) | Rare earth metal compounds, methods of making, and methods of using the same | |
| WO2002100419A1 (en) | Use of a phosphate adsorbent to combat vascular diseases | |
| Okazaki et al. | Complex phosphate adsorbent of MgO-TiO 2 | |
| JP2981574B2 (en) | Phosphate ion adsorbent | |
| JPH072903A (en) | Acetylated iron-chitosan complex, and its production and use | |
| JPH062580B2 (en) | Boehmite-like aluminum hydroxide, its production method and oral phosphate adsorbent containing it | |
| JPH0513092B2 (en) | ||
| US4918175A (en) | Bismuth (phosph/sulf)ated saccharides | |
| US4215143A (en) | Anti-ulcer pharmaceutical composition containing inositol hexasulfate aluminum or sodium aluminum salt as active ingredient |