Methods for the production of D-chiro-inositol and the use of D-chiro inositol obtained therefrom

• US 6,660,891 B2
• Filed: 05/11/2001
• Issued: 12/09/2003
• Est. Priority Date: 05/15/2000
• Status: Expired due to Fees

• Current Assignee: Insmed Incorporated
• Original Assignee: Insmed Incorporated
• Inventors: Miller, Paul, Sleevi, Mark C., Leonard, Patrick, Plourde, Robert, Johnson, Leland L. Jr., Campbell, A. S.
• Primary Examiner(s): Shippen, Michael L.
• Application Number:
  US09/853,032
• Publication Number:
  US 20020023877A1
• Time in Patent Office: 942 Days
• Field of Search: 568/833
• US Class Current: 568/833
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 29/88 by treatment giving rise to a chemical modification of at least one compound chemisorption C07C29/76
• CPC Class Codes: C07C 35/16 Inositols

Abstract

The present invention relates to methods for the production and isolation of D-chiro-inositol (DCI) from plant extracts. Specifically the present invention provides a method to produce D-chiro-inositol from a precursor moiety by conversion in concentrated hydrochloric acid. More specifically, the present invention relates to a method for the efficient production of DCI by a process involving the extraction of D-pinitol from soy hulls followed by conversion thereof to DCI.

Claims

1. A method to produce D-chiro-inositol comprising:

(a) preparing a reaction solution comprising a crude plant extract comprising a D-chiro-inositol precursor containing a D-chiro-inositol moiety selected from the group consisting of D-chiro-inositol, D-pinitol, ciceritol, 1D-2-O-alpha-D-galactopyranose-chiro-inositol, and fagopyritols in a solution of about 9 N to 12 N HCl; and

(b) reacting the solution of step (a) at a temperature in the range of about 65°

C. to about 110°

C. for a period of time sufficient to convert the D-chiro-inositol precursor to D-chiro-inositol.

2. The method of claim 1 wherein the reaction solution comprises a D-chiro-inositol precursor in a solution of about 9 N HCl.

3. The method of claim 1 wherein the reaction temperature is in the range of about 90°

C. to about 110°

C.

4. The method of claim 1 further comprising the steps:

(c) filtering the reaction solution of step (b) through decolorizing carbon;

(d) adjusting the solution of step (c) to a concentration of at least about 25% D-chiro-inositol; and

(e) precipitating the D-chiro-inositol from the reaction solution of step (d) with an aliphatic alcohol or mixture of at least two aliphatic alcohols.

5. The method of claim 4 wherein the D-chiro-inositol is precipitated by dilution of the solution of step (d) with about 2-fold to about 8-fold volume excess of the aliphatic alcohol or aliphatic alcohol mixture.

6. The method of claim 4 wherein the D-chiro-inositol is precipitated by dilution of the solution of step (d) with about 2-fold to about 8-fold volume excess of the aliphatic alcohol or aliphatic alcohol mixture while maintaining the resultant solution at a temperature of about 65°

C. to about 75°

C. during the course of alcohol dilution.

7. The method of claim 4 further comprising the steps;

(f) dissolving the precipitated D-chiro-inositol of step (e) in an aqueous solution; and

(g) removing contaminating ions with at least one ion exchange resin.

8. The method of claim 4 further comprising the steps;

(f) dissolving the precipitated D-chiro-inositol of step (e) in an aqueous solution and reprecipitating the D-chiro-inositol with and aliphatic alcohol or mixture of at least two aliphatic alcohols.

9. The method of claim 4 further comprising the steps;

(f) dissolving the precipitated D-chiro-inositol of step (e) in an aqueous solution;

(g) removing contaminating ions with at least one ion exchange resin; and

(h) reprecipitating the D-chiro-inositol with an aliphatic alcohol or mixture of at least two aliphatic alcohols.

10. A method to produce D-chiro-inositol comprising:

(a) preparing a reaction solution comprising a crude plant extract containing one or more carbohydrates or oligosaccarides, wherein the extract comprises a D-chiro-inositol moiety selected from the group consisting of D-chiro-inositol, D-pinitol, ciceritol, 1D-2-O-alpha-D-galactopyranose-chiro-inositol, and fagopyritols, in a solution of about 9 N to 12 N HCl; and

(b) reacting the solution of step (a) at a temperature in the range of about 90°

C. to about 110°

C. for a period of time sufficient to convert the D-chiro-inositol moiety to D-chiro-inositol.

11. The method of claim 10 further comprising:

(c) filtering the reaction solution of step (b) through decolorizing carbon;

(d) adjusting the solution of step (c) to a concentration of at least about 25% D-chiro-inositol; and

(e) precipitating the D-chiro-inositol from the reaction solution of step (d) by diluting the solution of step (d) with about 2-fold to about 8-fold volume excess of the aliphatic alcohol or a mixture of at least two aliphatic alcohols while maintaining the resultant solution at a temperature of about 65°

C. to about 75°

C. during the course of alcohol dilution.

12. The method of claim 10 wherein the plant extract is obtained from soy hulls.