Water-soluble coagulant drug vitamin k2 solid-state complex and preparation method thereof

A vitamin and procoagulant technology, applied in the field of medicine, to achieve the effect of improving solubility

Inactive Publication Date: 2017-03-22
YUNNAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, the inclusion of vitamin K with modified β-cyclodextrins is currently 2 The study of molecular solid-state complexes has not been reported, altho

Method used

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  • Water-soluble coagulant drug vitamin k2 solid-state complex and preparation method thereof
  • Water-soluble coagulant drug vitamin k2 solid-state complex and preparation method thereof
  • Water-soluble coagulant drug vitamin k2 solid-state complex and preparation method thereof

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Experimental program
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Embodiment

[0036] Mono-[6-(diethylenetriamine)-6-deoxy]-β-cyclodextrin and vitamin K involved 2 The solid complexes were synthesized as follows:

[0037] 1) Synthesis of mono-[6-(diethylenetriamine)-6-deoxy]-β-cyclodextrin 2 Mono-[6-(diethylenetriamine)-6-deoxy]-β-cyclodextrin For the detailed synthetic route, see Figure 14 (Synthesized according to literature, I.Tabushi, N.Shimizu, T.Sugimoto, M.Shiozuka, K.Yamamura, J.Am.Chem.Soc.1977,99,7100; I.Tabushi, N.Shimizu, Jpn.Kodai Tokkyo Koho 78 102 985, 1978 [Chem. Abstr., 1979, 90, 39196b]).

[0038] Into a 100mL dry round-bottomed flask, add 40mL of diethylenetriamine purified by distillation, add 5.0g of mono-(6-oxo-6-p-toluenesulfonyl)-β-cyclodextrin while stirring, protect with nitrogen, and dissolve Raise the temperature to about 76°C and react for 7 hours, then distill off most of the diethylenetriamine under reduced pressure, add the remaining liquid to acetone, collect the precipitate by suction filtration, repeat the operation...

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Abstract

The invention discloses a water-soluble coagulant drug vitamin k2 solid-state complex and a preparation method thereof, and belongs to the technical field of medicines. The product is a solid-state complex of mono-[6-(diethylenetriamine)-6-deoxy]-[beta]-cyclodextrin and vitamin K2 at a mixing ratio of 2 to 1. The mono-[6-(diethylenetriamine)-6-deoxy]-[beta]-cyclodextrin is obtained by adding mono-(6-o-6-p-toluenesulfonyl)-[beta]-cyclodextrin to diethylenetriamine, conducting a reaction in a mode of dissolving and increasing temperature in a nitrogen atmosphere, adding acetone after most diethylenetriamine is distilled so as to obtain a crude product, dissolving the crude product in a water and separating the dissolved product so as to obtain the mono-[6-(diethylenetriamine)-6-deoxy]-[beta]-cyclodextrin. A vitamin K2 acetone solution is added to a mono-[6-(diethylenetriamine)-6-deoxy]-[beta]-cyclodextrin water solution, and it conducts stirring at 35-40 DEG C in a sealed mode for 4.5-5.5 days so as to remove acetone and vitamin K2 failing to participate in inclusion. The obtained product (the solid-state complex) is low in toxicity; and the solubility of the vitamin K2, through inclusion, in water is increased by 110 times, and the product, as a vitamin K2 substitute, is applicable to the clinical field.

Description

technical field [0001] The invention belongs to the technical field of medicines, in particular to water-soluble procoagulant drug vitamin K 2 Solid state composite and method for its preparation. Background technique [0002] Vitamin K 2 (English name menaquinone) has the following structure: [0003] [0004] Refers to a family of homologues of 2-methyl-1,4-naphthoquinone, the third position of which is substituted by isopentenyl side chains containing 4 to 13 isoprene units, these are called menaquinones; The suffix (-4) indicates the number of isodiene units on the side chain. In 1934, Danish scientists first discovered vitamin K and confirmed that it was a fat-soluble vitamin. naturally occurring vitamin K 1 、K 2 , Vitamin K 1 Widely present in green plants, it is an important source of vitamin K in food; vitamin K 2 Mainly synthesized by intestinal bacteria. Vitamin K is biologically active in animals 2 , while vitamin K 1 and vitamin K 3 be converted in...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K31/122A61K47/40A61P7/04A61K47/69
CPCA61K31/122A61K9/146
Inventor 赵焱杨自明朱茜朱洪友阮琼郑萍尹华滔
Owner YUNNAN NORMAL UNIV
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