JPS63254102A - Ferrous ion ligand complex like chitosan derivatives - Google Patents
Ferrous ion ligand complex like chitosan derivativesInfo
- Publication number
- JPS63254102A JPS63254102A JP12712586A JP12712586A JPS63254102A JP S63254102 A JPS63254102 A JP S63254102A JP 12712586 A JP12712586 A JP 12712586A JP 12712586 A JP12712586 A JP 12712586A JP S63254102 A JPS63254102 A JP S63254102A
- Authority
- JP
- Japan
- Prior art keywords
- chitosan
- complex
- ferrous ion
- ferrous
- chitosan derivatives
- 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
- 229920001661 Chitosan Polymers 0.000 title claims description 27
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 title claims description 6
- 229910001448 ferrous ion Inorganic materials 0.000 title claims description 6
- 239000003446 ligand Substances 0.000 title 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 11
- 239000011790 ferrous sulphate Substances 0.000 claims description 11
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 11
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 230000001180 sulfating effect Effects 0.000 claims description 5
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims 2
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims 1
- 150000004696 coordination complex Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 23
- 229910052742 iron Inorganic materials 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000005670 sulfation reaction Methods 0.000 description 5
- 238000011282 treatment Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229920002101 Chitin Polymers 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010022971 Iron Deficiencies Diseases 0.000 description 1
- XEEYBQQBJWHFJM-BJUDXGSMSA-N Iron-55 Chemical compound [55Fe] XEEYBQQBJWHFJM-BJUDXGSMSA-N 0.000 description 1
- XEEYBQQBJWHFJM-AKLPVKDBSA-N Iron-59 Chemical compound [59Fe] XEEYBQQBJWHFJM-AKLPVKDBSA-N 0.000 description 1
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000000850 deacetylating effect Effects 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- RWOPUSRMJZAVNS-UHFFFAOYSA-N n-methylformamide;sulfurochloridic acid Chemical compound CNC=O.OS(Cl)(=O)=O RWOPUSRMJZAVNS-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000004313 potentiometry Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- -1 pyrinone Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000000196 viscometry Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
本発明は第一鉄イオン配位錯体状のキトサン誘導体類に
関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to chitosan derivatives in the form of ferrous ion coordination complexes.
更に詳しくは、本発明は第一鉄イオン配位錯体状のキト
サン誘導体類に関し、このものは水性媒体に可溶であり
、上記の鉄を胃腸管中に調整した仕方で放つことができ
る。More particularly, the present invention relates to chitosan derivatives in the form of ferrous ion coordination complexes, which are soluble in aqueous media and capable of releasing said iron into the gastrointestinal tract in a controlled manner.
上記誘導体類はＦｅ＋＋と残りのキトサン単位中の２位
置及び３位置にそれぞれ存在するアミノ基及び水酸基と
の間に配位結合を形成した錯体状の６−〇−硫酸塩型（
１）
（ただし、ｎは２５０ないし２３００である）のキトサ
ン類を含有する。The above derivatives are complex-like 6-〇-sulfate type (
1) Contains chitosan (where n is 250 to 2300).
キトサン（■）：
はキチンを強塩基処理により脱アセチル化して得られる
多糖類である。Chitosan (■): is a polysaccharide obtained by deacetylating chitin by treatment with a strong base.
キチン自身は、実質上、
のＮ−アセチル−Ｄ−ゲルコサミド単位からなる広く分
布している天然多糖類である。Chitin itself is a widely distributed natural polysaccharide consisting essentially of N-acetyl-D-gelcosamide units.
本発明に依る方法において使用されたキトサンは沸とう
状態の５０重量係のＮａＯＨ溶液で処理してカニの殻か
ら抽出したキチンから得られた。The chitosan used in the method according to the invention was obtained from chitin extracted from crab shells by treatment with a boiling 50% by weight NaOH solution.
粘度計法で定量したこのキトサンの分子量は５０．００
０ないし４００，０００であることが見出され、また電
位差計法で定量したその脱アセチル化度は８０ないし９
２％であることが見出された。The molecular weight of this chitosan determined by viscometry is 50.00.
0 to 400,000, and its degree of deacetylation, determined by potentiometric method, was found to be between 80 and 9.
It was found to be 2%.
本発明に依る、Ｆｅを調整放出する性質をもつ可溶性キ
トサン誘導体類の製法は下記の諸工程を宮む：
ａ）キトサン（ＩＩ）を有機酸に溶解し：ｂ）硫酸第一
鉄溶液を加えて上記配位錯体を沈殿させ；
Ｃ）この沈殿錯体を濾過、洗浄、乾燥し：ｄ）この錯体
を、５０３−有機塩基又はクロルスルホン酸−メチルホ
ルムアミド錯体で処理して硫酸化する、諸工程。The method for producing soluble chitosan derivatives with controlled Fe release properties according to the present invention involves the following steps: a) dissolving chitosan (II) in an organic acid; b) adding a ferrous sulfate solution. c) filtering, washing and drying the precipitated complex; d) sulfating the complex by treating it with a 503-organic base or a chlorosulfonic acid-methylformamide complex; .
上記キトサンを、■程ａ）に依り、１ないし５容量チの
濃度の有機酸、好ましくは酢酸又はギ酸中で周囲温度で
溶解する。The chitosan is dissolved according to step a) in a concentration of 1 to 5 volumes of organic acid, preferably acetic acid or formic acid, at ambient temperature.
工程ｂ）は、工程ａ）の溶液に上記キトサンの１ないし
５倍のモル量の硫酸第一鉄溶液を加え、２ないし７のｐ
Ｈで１０ないし２５℃の温度で攪拌下に２ないし１６時
間、作用させて行なわれる。In step b), a ferrous sulfate solution with a molar amount of 1 to 5 times that of the above chitosan is added to the solution of step a), and a ferrous sulfate solution with a molar amount of 2 to 7
The reaction is carried out under stirring at a temperature of 10 to 25° C. for 2 to 16 hours.
上記の反応から生じた混合物をＥ過して沈殿錯体を回収
し、これを水とメタノールで洗浄し、ついで真空下に４
０ないし５０℃で乾燥する。The mixture resulting from the above reaction was filtered with E-filter to recover the precipitated complex, which was washed with water and methanol and then vacuumed for 44 hours.
Dry at 0 to 50°C.
■程ｄ）の硫酸化反応は、硫酸化剤として三酸化イオウ
と有機塩基、例えばピリノン、トリエチルアミン又はジ
メチルホルムアミドとの錯体又はりｏ Ａ／ スルホン
酸トホルムアミド、ジメチルホルムアミド又は他の有機
塩基との錯体を用いて、無水のジメチルホルムアミドか
らなる媒体中で行なわれる。■ The sulfation reaction in step d) can be carried out using a complex of sulfur trioxide and an organic base, such as pyrinone, triethylamine or dimethylformamide, or a complex of sulfonic acid with toformamide, dimethylformamide or another organic base as the sulfating agent. The complex is carried out in a medium consisting of anhydrous dimethylformamide.
上記硫酸化反応は０ないし２℃の温度で２０ないし６０
分間、ついで周囲温度で１６ないし４８時間、行なわれ
る。The above sulfation reaction is carried out at a temperature of 0 to 2°C for 20 to 60°C.
for 16 to 48 hours at ambient temperature.
硫酸化反応は、０ないし２℃で２０ないし６０分間、つ
いで周囲温度で１６ないし４８時間、行なわれる。The sulfation reaction is carried out at 0 to 2° C. for 20 to 60 minutes, then at ambient temperature for 16 to 48 hours.
この期間の終りに、硫酸化後に得られた混合物をＮａＨ
ＣＯｓ又はＫＯＨの如き無機塩基で中和し、ついで、存
在する有機塩基及び無機塩が完全に除去されるまで水で
透析する。At the end of this period, the mixture obtained after sulfation was diluted with NaH
Neutralization with an inorganic base such as COs or KOH followed by dialysis against water until the organic base and inorganic salts present are completely removed.
得られた生成物は０．８５ないし１．０の置換度及び４
ないし１５俤の鉄含有率を持っている。分子量は５０，
０００ないし４００，０００であり、このことは本発明
の条件下の上記硫酸化反応が、上記多糖類分子の分解に
進まないことを示している。The product obtained has a degree of substitution of 0.85 to 1.0 and a
It has an iron content of 15 to 15 yen. The molecular weight is 50,
000 to 400,000, indicating that the sulfation reaction under the conditions of the present invention does not proceed to decomposition of the polysaccharide molecule.
硫酸化形のこの生成物は高い溶解度を持ち、それ故、鉄
欠乏を補償するための治療の際に溶液として使用できる
。The sulfated form of this product has a high solubility and can therefore be used as a solution in treatments to compensate for iron deficiency.
本発明に依るキトサン誘導体類中含有鉄の人体吸収を評
価するため、我々は、標識鉄Ｆｅ ５５及びＦｅ５９を
使用する。Ｈ，Ｂｒ１ｃｅ及びり、 Ｈａｌｌｅｎｂｅ
ｒｇによシ記述された方法（ＡｃＴｉ Ｍｅｄ、 ５ｃ
ａｎｄ、 ５ｕｐｐ１．３７６゜１７１ ニア−２２，
１９６２）を用いた。この方法により、同時に同じ被検
者による、２個のＦｅに基づく生成物の吸収を研究する
ことができる。To evaluate the human absorption of iron contained in the chitosan derivatives according to the present invention, we use labeled iron Fe55 and Fe59. H, Br1ce and Hallenbe
The method described by AcTi Med, 5c
and, 5upp1.376°171 near-22,
1962) was used. This method allows the absorption of two Fe-based products to be studied by the same subject at the same time.
正常のシデレミア（Ｓｉｄｅｒｅｍｉａ ） トシｆ０
フィリンを持つ８名の健康な被検者に対し、我々は、一
つの同位元素で標識した硫酸第一鉄３０■を経口投与し
、翌日、我々は他の同位元素を含有する本発明に依るキ
トサン誘導体、生成物Ａとしての鉄を同量投与した。Normal Sideremia (Sideremia) Toshi f0
To eight healthy subjects with filin, we orally administered 30 μ of ferrous sulfate labeled with one isotope, and the next day we administered 30 μl of ferrous sulfate labeled with one isotope. The chitosan derivative, iron as product A, was administered in the same amount.
ついで我々は上記二つの調剤からの鉄の吸収率（チ）を
調べた（第１表）。We then investigated the iron absorption rate (Q) from the above two preparations (Table 1).
第１表から、生成物Ａに含有の鉄が腸水準において、硫
酸第一鉄に含有の鉄のチよりも決定的に大きい係で吸収
されることがわかる。It can be seen from Table 1 that the iron contained in product A is absorbed at a significantly greater rate at the intestinal level than the iron contained in ferrous sulfate.
第１表
硫酸第一鉄中に及び生成物Ａ中に含有の鉄の腸吸収被検
者 吸収
Ｆｅ ＳＯ４生成物Ａ
Ｍｌ ９．２ １１．６Ｒ
Ｄ ４．５ ８．９ＴＷ
７．９ １０．８ＡＮ
２０，４ ２３．２ＢＦ
１５．１ １７．４ＧＤ
５．６ ６．２Ｆ Ｅ
７．５ ８．０ＡＮ
６．４ ７．８Ｍ ９
．５７ １１．７３ＤＳ ５
．４３ ５．７６Ｐ”
＜０．０５平坦化データについ
てのスチューデントのｔ試験生成物Ａの許容性を決定す
るため、鉄欠乏性貧血の３０名の老人症患者に、平均３
８日の期間、鉄を６０〜７日の投与量で投与した。食事
に義務的（］０）
に関連させずに、患者の好みに応じて１日に１回又は２
回、生成物Ａを水溶液として摂取させた。Table 1 Intestinal absorption of iron in ferrous sulfate and in product A Subject Absorbed Fe SO4 Product A Ml 9.2 11.6R
D 4.5 8.9TW
7.9 10.8AN
20,4 23.2BF
15.1 17.4GD
5.6 6.2F E
7.5 8.0AN
6.4 7.8M 9
．． 57 11.73DS 5
．． 43 5.76P”
To determine the acceptability of the Student's t test Product A for <0.05 flattened data, 30 geriatric patients with iron deficiency anemia were given an average of 3
Iron was administered at doses ranging from 60 to 7 days over a period of 8 days. Once or twice a day, depending on patient preference, without obligatory (]0) connection to meals.
Product A was taken as an aqueous solution twice.
治療はすべての患者に対して至極良好に許容され、かつ
消化不良、腸又は他の障害についての訴えは全くなかっ
た。The treatment was very well tolerated by all patients and there were no complaints of dyspepsia, intestinal or other disorders.
シデレミアは平均増加率２１係を受け、ヘモグロビンが
増加し、患者の自覚症状が改善された。Sideremia received an average increase rate of 21, hemoglobin increased, and patients' subjective symptoms improved.
本発明によるキトサン誘導体類の製法の一実施例を非限
定的例示のため、以下に記載する。An example of the method for producing chitosan derivatives according to the invention is described below for non-limiting illustration.
実施例１
分子量３５０，０００でアセチル化度８ｏ係のキトサン
１００ｇを２容量係のギ酸水溶液５００７！に周囲温度
で溶解する。Example 1 100 g of chitosan with a molecular weight of 350,000 and a degree of acetylation of 8 degrees was mixed with 2 volumes of a formic acid aqueous solution of 5007! Soluble at ambient temperature.
生成溶液に磯度３３０ｇ／ｌの硫酸第一鉄溶液５゜−を
加え、ＰＨ２，５の溶液を得、これを攪拌下に２５℃の
温度で１６時間、保持する。A 5° solution of ferrous sulfate with a degree of roughness of 330 g/l is added to the resulting solution to obtain a solution with a pH of 2.5, which is kept under stirring at a temperature of 25° C. for 16 hours.
反応混合物を濾過してキトサン誘導体を回収し、これを
水洗し、ついで真空下４０℃で乾燥する。The reaction mixture is filtered to recover the chitosan derivative, which is washed with water and then dried under vacuum at 40°C.
かくして得た生成物を無水ジメチルホルムアミド４０〇
−中に分散させ、５０３−ピリジン錯体７．６ｙを加え
、混合物を攪拌下に１℃の温度で４０分間、ついで周囲
温度で３５時間、保持する。The product thus obtained is dispersed in 40° of anhydrous dimethylformamide, 7.6 y of 503-pyridine complex are added and the mixture is kept under stirring at a temperature of 1° C. for 40 minutes and then at ambient temperature for 35 hours.
かくして得た反応混合物を１０重量係のＮａ ＨＣＯ３
溶液を加えて中和し、ついで、存在する有機塩基及び無
機塩が完全に除去されるまで水で透析する。The reaction mixture thus obtained was mixed with 10 parts by weight of NaHCO3.
The solution is added to neutralize and then dialyzed against water until the organic base and inorganic salts present are completely removed.
生成物を真空下に乾燥して回収する。The product is recovered by drying under vacuum.
この方法で、下記の特性をもつキトサン誘導体１４．５
１１を得た：
硫酸塩基の置換度 ０９
鉄含有率 ９係In this method, a chitosan derivative 14.5 with the following properties can be obtained.
Obtained 11: Degree of substitution of sulfate base 09 Iron content rate 9
Claims (8)
及び３位置にそれぞれ存在するアミノ基及び水酸基との
間に配位結合を形成した錯体類状の、６−Ｏ−硫酸塩型
のキトサン類（ I ） ▲数式、化学式、表等があります▼（ I ） （ただし、ｎは２５０ないし２３００である） のキトサン類を含有する第一鉄イオン配位錯体類状のキ
トサン誘導体類。(1) A 6-O-sulfate type complex in which coordinate bonds are formed between Fe^+^+ and the amino group and hydroxyl group present at the 2- and 3-positions of the chitosan glucosamide ring, respectively. Chitosan (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (However, n is 250 to 2300) Chitosan derivatives in the form of ferrous ion coordination complexes containing chitosan.
強無機塩基で処理する、諸工程で行なうことを特徴とす
る、 Ｆｅ＾＋＾＋とキトサングルコサミド環の２位置及び３
位置にそれぞれ存在するアミノ基及び水酸基との間に配
位結合を形成した錯体類状の、６−Ｏ−硫酸塩型（ I
） ▲数式、化学式、表等があります▼（ I ） （ただし、ｎは２５０ないし２３００である） のキトサン類を含有する第一鉄イオン配位錯体類状のキ
トサン誘導体類の製造方法。(2) The following steps: a) Dissolve chitosan (II) ▲Mathematical formula, chemical formula, table, etc.▼(II) in an organic acid; b) Add ferrous sulfate solution to precipitate the coordination complex; c) filtering, washing and drying the precipitated complex; d) sulfating the dried complex with an organic base and then treating it with a strong inorganic base. 2 and 3 positions of the glucosamide ring
6-O-sulfate type (I
) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (However, n is 250 to 2300) A method for producing chitosan derivatives in the form of ferrous ion coordination complexes containing chitosan.
はギ酸に周囲温度で溶解させることを特徴とする、特許
請求の範囲第（１）項に記載の方法。(3) Process according to claim 1, characterized in that the chitosan is dissolved in acetic acid or formic acid at a concentration of 1 to 5% by volume at ambient temperature.
濃度の硫酸第一鉄溶液状で添加し、２ないし７のｐＨで
５ないし２５℃の温度で作用させることを特徴とする、
特許請求の範囲第（２）項に記載の方法。(4) The ferrous sulfate is added in the form of a ferrous sulfate solution with a concentration of 200 to 600 g/l, and is allowed to act at a pH of 2 to 7 and a temperature of 5 to 25°C.
A method according to claim (2).
１ないし５であることを特徴とする、特許請求の範囲第
（２）項に記載の方法。(5) The method according to claim (2), characterized in that the weight ratio of the chitosan to the added FeSO_4 is from 1 to 5.
リジン、トリメチルアミン又はジメチルホルムアミドと
の錯体を無水ジメチルホルムアミドからなる反応媒体中
で使用することにより、上記乾燥錯体を硫酸化すること
を特徴とする、特許請求の範囲第（２）項に記載の方法
。(6) The dry complex is sulfated by using a complex of sulfur trioxide and a weak base such as pyridine, trimethylamine or dimethylformamide as a sulfating agent in a reaction medium consisting of anhydrous dimethylformamide. The method according to claim (2).
又はジメチルホルムアミドとの錯体を用いて上記乾燥錯
体を硫酸化することを特徴とする、特許請求の範囲第（
２）項に記載の方法。(7) The dry complex is sulfated using a complex of chlorosulfonic acid and formamide or dimethylformamide as a sulfating agent.
The method described in section 2).
り定義し、調製した第一鉄イオン配位錯体状のキトサン
誘導体類を含有する医薬組成物。(8) A pharmaceutical composition containing chitosan derivatives in the form of ferrous ion coordination complexes defined and prepared according to claims (1) to (7).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12712586A JPH0240242B2 (en) | 1985-03-14 | 1986-05-30 | DAIICHITETSUIONHAIISAKUTAIJONOKITOSANJUDOTAIRUI |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT19916/85A IT1184161B (en) | 1985-03-14 | 1985-03-14 | CHITOSAN DERIVATIVES CONSTITUTED BY COORDINATION COMPLEXES WITH FERROUS IONS |
| JP12712586A JPH0240242B2 (en) | 1985-03-14 | 1986-05-30 | DAIICHITETSUIONHAIISAKUTAIJONOKITOSANJUDOTAIRUI |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63254102A true JPS63254102A (en) | 1988-10-20 |
| JPH0240242B2 JPH0240242B2 (en) | 1990-09-11 |
Family
ID=26327345
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12712586A Expired - Lifetime JPH0240242B2 (en) | 1985-03-14 | 1986-05-30 | DAIICHITETSUIONHAIISAKUTAIJONOKITOSANJUDOTAIRUI |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0240242B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997047323A3 (en) * | 1996-06-11 | 1998-04-23 | Zonagen Inc | Chitosan drug delivery system |
-
1986
- 1986-05-30 JP JP12712586A patent/JPH0240242B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997047323A3 (en) * | 1996-06-11 | 1998-04-23 | Zonagen Inc | Chitosan drug delivery system |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0240242B2 (en) | 1990-09-11 |
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