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Patent Searching and Data


Title:
INSULIN MIMETICS FROM HONEY
Document Type and Number:
WIPO Patent Application WO/2000/039135
Kind Code:
A2
Abstract:
The use of honey as a source material of P and A-type inositolphosphoglycans (IPGs) is disclosed, together with P and A-type cyclitol containing carbohydrates isolated from honey having the biological activities of activating PDH phosphatase or inhibiting cAMP dependent protein kinase and regulating lipogenesis respectively.

Inventors:
TABIDI IKHLAS (GB)
GUMAA KHALID (GB)
Application Number:
PCT/GB1999/004378
Publication Date:
July 06, 2000
Filing Date:
December 23, 1999
Export Citation:
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Assignee:
RADEMACHER GROUP LIMITED (GB)
TABIDI IKHLAS (GB)
GUMAA KHALID (GB)
International Classes:
A61K35/04; A61K35/64; A61K35/644; C07G3/00; (IPC1-7): C07G3/00
Domestic Patent References:
WO1998011116A11998-03-19
WO1998011117A11998-03-19
Other References:
S.W. HOMANS ET AL.: "Complete structure of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein" NATURE, vol. 333, 1988, pages 269-272, XP002140288
K. HORVATH ET AL.: "Simultaneous quantitation of mono-, di-, and trisaccharides by GC-MS of their TMS ether oxime derivatives: II. In honey" CHROMATOGRAPHIA, vol. 45, 1997, pages 328-335, XP000920509 cited in the application
Attorney, Agent or Firm:
Kiddle, Simon J. (Mewburn Ellis York House 23 Kingsway London WC2B 6HP, GB)
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Claims:
Claims:
1. A substance as obtainable from honey, wherein the substance is a cyclitol containing carbohydrate which is: (i) a Ptype substance having the biological activity of activating pyruvate dehydrogenase (PDH) phosphatase; or, (ii) an Atype substance having the biological activity of regulating lipogenic activity and inhibiting cAMP dependent protein kinase.
2. The substance of claim 1 as obtainable from honey by: (a) making an extract by heat and acid treatment of honey; (b) after centrifugation and charcoal treatment, allowing the resulting solution to interact overnight with an AG1X8 (formate form) anion exchange resin ; (c) collecting a fraction having Atype substance activity. obtained by eluting the column with 50mM HC1 (pH 1.3) and/or collecting a fraction having Ptype substance activity obtained by eluting the column with lOmM HC1 (pH 2.0); (d) neutralising to pH 4 (not to exceed pH 7.8) and lyophilising the fraction to isolate the substance; (e) employing descending paper chromatography using 4/1/1 butanol/ethanol/water as solvent; (f) purification using high voltage paper electrophoresis in pyridine/acetic acid/water; and, (g) purification and isolation using Vydac HPLC chromatography to obtain the isolated P or Atype substance.
3. The substance of claim 1 or claim 2 for use in a method of medical treatment.
4. Use of honey as a source material for a P or Atype substance, wherein the substance is a cyclitol containing carbohydrate which is: (i) a Ptype substance having the biological activity of activating pyruvate dehydrogenase (PDH) phosphatase; or, (ii) an Atype substance having the biological activity of regulating lipogenic activity and inhibiting cAMP dependent protein kinase.
5. A pharmaceutical composition comprising one or more of the substances of claim 1 or claim 2.
6. Use of a substance of claim 1 or claim 2 for the preparation of a medicament for the treatment of a condition characterised by a deficiency or imbalance of IPGs.
7. The use of claim 6, wherein the condition is diabetes.
8. The use of claim 7, wherein the diabetes is diabetes due to insulin resistance (Type II diabetes), Type I diabetes, or brittle diabetes.
9. The use of claim 6, wherein the condition is a lipotrophic disorder.
10. The use of claim 6, wherein the condition. is polycystic ovary disease.
11. Use of cellulose chromatography for purifying or isolating a P or Atype substance, wherein the substance is a cyclitol containing carbohydrate which is: (i) a Ptype substance having the biological activity of activating pyruvate dehydrogenase (PDH) phosphatase; or, (ii) an Atype substance having the biological activity of inhibiting cAMP dependent protein kinase.
12. The use of claim 11, wherein the use involves contacting a sample containing P or Atype substance with a column containing cellulose and eluting the substance from the column.
13. The use of claim 11 or claim 12, wherein the column comprises microcrystalline cellulose.
14. A method of purifying or isolating a P or Atype substance, wherein the substance is a cyclitol containing carbohydrate which is: (i) a Ptype substance having the biological activity of activating pyruvate dehydrogenase (PDH) phosphatase; or, (ii) an Atype substance having the biological activity of inhibiting cAMP dependent protein kinase; wherein the method comprises: (a) loading a column containing cellulose with a sample containing the P or Atype substance so that P or Atype substance binds to the column; and, (b) eluting the P or Atype substance from the column.
15. The method of claim 14, wherein the cellulose is microcrystalline cellulose.
16. The method of claim 14 or claim 15 further comprising the step of dissolving the sample containing the P or Atype substance in 4/1/1 butanol/water/ethanol (B: W: E) prior loading on the column.
17. The method of any one of claims 14 to 16, further comprising the step of washing the column with B: W: E and methanol.
18. The method of any one of claims 14 to 17, wherein the P or Atype substance is eluted with water and HC1.
Description:
INTERNATIONAL SEARCH REPORT-------- PCT/GB 99/04378 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category-Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. A S. W. HOMANS ET AL. :"Complete structure 1,3, 11 of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein" NATURE, vol. 333, 1988, pages 269-272, XP002140288 the whole document A K. HORVATH ET AL. :"Simultaneous 1,3, 11 quantitation of mono-, di-, and trisaccharides by GC-MS of their TMS ether oxime derivatives: II. In honey" CHROMATOGRAPHIA, vol. 45, 1997, pages 328-335, XP000920509 cited in the application figures 1 and 2; tables 2-4 8 (national application No. PCT/GB 99/04378 INTERNATIONAL SEARCH REPOrT Box I Observations where certain claims were found unsearchable (Continuation of item 1 of first sheet) This international Search Report has not been established in respect of certain claims under Article 17 (2) (a) for the following reasons: 1. Claims Nos.: because they relate to subject matter not required to be searched by this Authority, namely: 2. Claims Nos.: because they relate to parts of the International Application that do not comply with the prescribed requirements to such an extent that no meaningful International Search can be carried out, specifically: 3. Claims Nos.: because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4 (a). Box 11 Observations where unity of invention is lacking (Continuation of item 2 of first sheet) This International Searching Authority found multiple inventions in this international application, as follows: 1. As all required additional search fees were timely paid by the applicant, this International Search Report covers all searchable claims. 2. As all searchable claims could be searched without effort justifying an additional fee, this Authority did not invite payment of any additional fee. 3. As only some of the required additional search fees were timely paid by the applicant, this International Search Report covers only those claims for which fees were paid, specifically claims Nos.: 4. g No required additional search fees were timely paid by the applicant. Consequently, this International Search Report is restricted to the invention first mentioned in the claims; it is covered by claims Nos.: 1-10 (full) 11-18 (in part) Remark on Protest The additional search fees were accompanied by the appticant's protest. # No protest accompanied the payment of additional search fees.

FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 1. Claims: 1-10 (in full) 11-18 (in part) Pertaining to substances which can be isolated from honey.

2. Claims: 11-18 (in part) Pertaining to substances which may be isolated from any source other than honey. INTERNATIONAL SEARCH REPORT ntf ional Application No -"-*"tntf jona! ApphcatonNo nformation on patent family members Patent document Publication Patent family Publication cited in search report date member (s) date WO 9811116 A 19-03-1998 AT 192161 T 15-05-2000 AU 713103 B 25-11-1999 AU 4130797 A 02-04-1998 DE 69701812 D 31-05-2000 EP 0925305 A 30-06-1999 WO 9811117 A 19-03-1998 AT 192160 T 15-05-2000 AU 713100 B 25-11-1999 AU 4310197 A 02-04-1998 DE 69701811 D 31-05-2000 EP 0925304 A 30-06-1999