Use of tomato extract as antihypertensive agent and process for making water soluble sugar free tomato extract

Abstract

Provided herein is technology relating to tomato extracts and particularly, but not exclusively to preparing and using tomato extracts as an anti-hypertensive agent to modulate blood pressure.

We claim: 
     
         1 . A composition comprising a water-soluble, sugar-free tomato extract or an active fraction thereof. 
     
     
         2 . The composition of  claim 1  wherein the active components of the composition have a molecular mass less than 1000 Da. 
     
     
         3 . The composition of  claim 1  or  2 , essentially free of lycopene. 
     
     
         4 . The composition of any of  claims 1  to  3  in the form of a dried powder. 
     
     
         5 . The composition of any of  claims 1  to  3  in the form of a solution that will pass through a 0.2 μm filter without loss of solids. 
     
     
         6 . The composition of any of  claims 1  to  5  essentially free of nucleosides. 
     
     
         7 . The composition of any of  claims 1  to  6  formulated for oral administration. 
     
     
         8 . The composition of any of  claims 1  to  7  formulated in a form selected from the group consisting of a solution, a suspension, a syrup, a tablet, a capsule, a lozenge, a snack bar, a health drink, an insert, and a patch. 
     
     
         9 . A method of manufacturing a tomato extract, the method comprising the steps of:
 a) homogenizing a tomato to produce a tomato homogenate;   b) filtering the tomato homogenate through a filter having a molecular weight cutoff of 1000 Da to produce a filtrate; and   c) collecting the filtrate to provide an extract.   
     
     
         10 . The method of  claim 9  further comprising freeze-drying the homogenate to produce a freeze-dried homogenate and dissolving the freeze-dried homogenate in water. 
     
     
         11 . The method of any of  claims 9  to  10  further comprising freeze-drying the filtrate to produce a freeze-dried filtrate and dissolving the freeze-dried filtrate in water. 
     
     
         12 . The method of any of  claims 9  to  11  further comprising removing a water-soluble sugar from the extract. 
     
     
         13 . A composition comprising a tomato extract, obtainable by a method comprising the steps of:
 a) homogenizing a tomato to produce a tomato homogenate;   b) filtering the tomato homogenate through a filter having a molecular weight cutoff of 1000 Da to produce a filtrate;   c) collecting the filtrate to provide an extract; and   d) removing a water-soluble sugar from the extract.   
     
     
         14 . A composition comprising a tomato extract for use as a medicament to treat hypertension. 
     
     
         15 . A composition comprising a tomato extract for use as a medicament to inhibit angiotensin converting enzyme (ACE). 
     
     
         16 . The composition of any of  claim 13  or  15  wherein the composition is a water-soluble, sugar-free tomato extract. 
     
     
         17 . The composition of any of  claim 13  or  15  wherein the tomato extract is made from a cold-break tomato paste. 
     
     
         18 . The composition of  14  or  15  produced by a process comprising the steps of:
 a) diluting in water a cold-break tomato paste of 28-30° Brix and a browning index less than 0.350 AU; 
 b) removing particulate matter greater than 0.2 μm to produce a solution; and 
 c) concentrating the solution to form a syrup of 62-65° Brix. 
 
     
     
         19 . The composition of  claim 14  or  15  produced by a process comprising the steps of:
 a) homogenizing tomatoes; 
 b) removing particulates by centrifugation and/or ultrafiltration; and 
 c) removing soluble sugars. 
 
     
     
         20 . The composition of  claim 19 , wherein the process further comprises fractionating the non-sugar components using high-pressure liquid chromatography. 
     
     
         21 . A pharmaceutical formulation comprising a tomato extract or an active component thereof and a pharmaceutically acceptable carrier suitable for treating hypertension or for inhibiting ACE, wherein said tomato extract or active fraction thereof is selected from the group consisting of juices, pastes, sauces, soups and compositions as described in any of  claims 1  to  8 . 
     
     
         22 . An anti-hypertension agent comprising a tomato extract or active fraction thereof, wherein said tomato extract or active fraction thereof is selected from the group consisting of juices, pastes, sauces, soups and compositions as described in any of  claims 1  to  8 . 
     
     
         23 . An ACE inhibitor comprising a tomato extract or active fraction thereof, wherein said tomato extract or active fraction thereof is selected from the group consisting of juices, pastes, sauces, soups and compositions as described in any of  claims 1  to  8 . 
     
     
         24 . A method of treating a subject comprising:
 a) identifying a subject having or at risk of having a condition associated with hypertension or ACE activity; and   b) administering a composition comprising a tomato extract or active fraction thereof to said subject.   
     
     
         25 . The method of  claim 24  wherein the tomato extract inhibits ACE. 
     
     
         26 . The method of any of  claims 24  to  25  wherein the tomato extract is an aqueous extract. 
     
     
         27 . The method of any of  claims 24  to  26  wherein the tomato is peeled prior to the step of homogenizing. 
     
     
         28 . The method of any of  claims 24  to  27  wherein the tomato extract is in the form of a concentrate or a dehydrate. 
     
     
         29 . The method of any of  claims 24  to  28  wherein the tomato extract is in the form of a concentrate which is at least 2-fold concentrated. 
     
     
         30 . The method of  29  wherein the tomato extract has been dehydrated to give a dry extract. 
     
     
         31 . The method of  claim 30  wherein the dry extract is in the form of a solid or semisolid dosage form. 
     
     
         32 . The method of any of  claims 24  to  31  wherein the extract is contained within a capsule shell. 
     
     
         33 . The method of any of  claims 24  to  32  wherein the extract contains a substantially heat stable water soluble compound or compounds having a molecular weight of less than 1000. 
     
     
         34 . The method of any of  claims 24  to  33  wherein the condition or disorder is selected from the group consisting of stroke, aneurysm, coronary heart disease (CHD), heart attack, atherosclerosis, ischemic heart disease, left ventricular hypertrophy, encephalopathy, congestive heart failure, hypertensive retinopathy, gout, tachycardia, kidney dysfunction, diabetes, and disease states associated with ACE activity and/or hypertension. 
     
     
         35 . The method of any of  claims 24  to  34 , wherein the extract is in the form of an active fraction of the fruit capable of passing through an ultrafiltration filter having a molecular weight cut-off of 1000 and containing a substantially heat stable, colorless or straw-colored, water soluble compound or compounds having a molecular weight of less than 1000. 
     
     
         36 . The method of any of  claims 24  to  35 , wherein said composition comprising a tomato extract or active fraction thereof is selected from the group consisting of juices, pastes, sauces, and soups. 
     
     
         37 . A method for the treatment a condition associated with hypertension, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a fruit extract having anti-hypertension activity, and wherein the fruit extract is obtained from a fruit of the plant family Solanaceae by a process comprising the steps of homogenizing the flesh of the fruit to form a homogenate and removing solids therefrom. 
     
     
         38 . The use of a composition of any one of  claims 1 - 8  for the manufacture of a medicament for use in treating a condition or disease state associated with hypertension or ACE activity. 
     
     
         39 . The use of  claim 38  wherein the condition or disease state is selected from the group consisting of stroke, aneurysm, coronary heart disease (CHD), heart attack, atherosclerosis, ischemic heart disease, left ventricular hypertrophy, encephalopathy, congestive heart failure, hypertensive retinopathy, gout, tachycardia, kidney dysfunction, diabetes, and disease states associated with ACE activity and/or hypertension. 
     
     
         40 . A process for the manufacture of a medicament for use in treating hypertension or inhibiting ACE comprising using a tomato extract or an active fraction thereof as defined in any one of  claims 1  to  8 . 
     
     
         41 . The composition of  claim 1  which is at least 2-fold concentrated, or at least 4-fold concentrated, or at least 8-fold, or at least 40-fold, or at least 100-fold, or at least 200-fold, or at least 1000-fold concentrated. 
     
     
         42 . The pharmaceutical formulation of  claim 21  in the form of a tablet, lozenge, capsule, powder, granulate, or gel. 
     
     
         43 . The pharmaceutical formulation of  claim 21  in the form of a unit dosage. 
     
     
         44 . A composition comprising a tomato extract or an active component or fraction thereof for promoting cardiovascular health. 
     
     
         45 . A composition for promoting cardiovascular health produced by a process comprising:
 a) homogenizing tomatoes;   b) removing particulates by centrifugation and/or ultrafiltration; and   c) removing soluble sugars.   
     
     
         46 . A process for the manufacture of a composition for use in promoting cardiovascular health, the process comprising using a tomato extract or an active fraction thereof as defined in any one of  claims 1  to  8 . 
     
     
         47 . A method of treating a subject comprising:
 a) identifying a subject having or at risk of having a condition associated with high blood pressure; and   b) administering a composition comprising a tomato extract or active fraction thereof to said subject.   
     
     
         48 . A method for the reduction of blood pressure, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a fruit extract having blood pressure lowering activity, and wherein the fruit extract is obtained from a fruit of the plant family Solanaceae by a process comprising the steps of homogenizing the flesh of the fruit to form a homogenate and removing solids therefrom. 
     
     
         49 . The method of  claim 48  wherein the fruit extract inhibits ACE. 
     
     
         50 . The method of any of  claims 48  to  49  wherein the fruit is a tomato. 
     
     
         51 . The method of any of  claims 48  to  50  wherein the fruit extract is an aqueous extract. 
     
     
         52 . The method of any of  claims 48  to  51  wherein the tomato is peeled prior to the step of homogenizing. 
     
     
         53 . The method of any of  claims 48  to  52  wherein the fruit extract is in the form of a concentrate or a dehydrate. 
     
     
         54 . The method of  claim 53  wherein the extract is in the form of a concentrate which is at least 2-fold concentrated. 
     
     
         55 . The method of  claim 53  wherein the extract has been dehydrated to give a dry extract. 
     
     
         56 . The method of  claim 55  wherein the dry extract is in the form of a solid or semisolid dosage form. 
     
     
         57 . The method of any of  claims 48  to  56  wherein the extract is contained within a capsule shell. 
     
     
         58 . The method of any of  claims 48  to  57  wherein the extract contains a substantially heat stable water soluble compound or compounds having a molecular weight of less than 1000. 
     
     
         59 . The method of any of  claims 48  to  58 , wherein the extract is in the form of an active fraction of the fruit capable of passing through an ultrafiltration filter having a molecular weight cut-off of 1000 and containing a substantially heat stable, colorless or straw-colored, water soluble compound or compounds having a molecular weight of less than 1000. 
     
     
         60 . The use of a composition of any one of  claims 1 - 8  for the manufacture of a medicament for use in treating a condition or disease state associated with high blood pressure. 
     
     
         61 . A process for the manufacture of a medicament for use in lowering blood pressure comprising using a tomato extract or an active fraction thereof as defined in any one of  claims 1  to  8 . 
     
     
         62 . Use of a composition comprising a tomato extract or active fraction thereof for treatment of a condition associated with hypertension or ACE activity. 
     
     
         63 . Use of  claim 62 , wherein the tomato extract is an aqueous extract. 
     
     
         64 . Use of any of  claims 62  to  63 , wherein the tomato is peeled prior to the step of homogenizing. 
     
     
         65 . Use of any of  claims 62  to  64 , wherein the tomato extract is in the form of a concentrate or a dehydrate. 
     
     
         66 . Use of  claim 65 , wherein the extract is in the form of a concentrate which is at least 2-fold concentrated. 
     
     
         67 . Use of  claim 66 , wherein the extract has been dehydrated to give a dry extract. 
     
     
         68 . Use of  claim 67 , wherein the dry extract is in the form of a solid or semisolid dosage form. 
     
     
         69 . Use of any of  claims 62  to  68 , wherein the extract is contained within a capsule shell. 
     
     
         70 . Use of any of  claims 62  to  69 , wherein the extract contains a substantially heat stable water soluble compound or compounds having a molecular weight of less than 1000. 
     
     
         71 . Use of any of  claims 62  to  70 , wherein the condition or disorder is selected from the group consisting of stroke, aneurysm, coronary heart disease (CHD), heart attack, atherosclerosis, ischemic heart disease, left ventricular hypertrophy, encephalopathy, congestive heart failure, hypertensive retinopathy, gout, tachycardia, kidney dysfunction, diabetes, and disease states associated with ACE activity and/or hypertension. 
     
     
         72 . Use of any of  claims 62  to  71 , wherein the extract is in the form of an active fraction of the fruit capable of passing through an ultrafiltration filter having a molecular weight cut-off of 1000 and containing a substantially heat stable, colorless or straw-colored, water soluble compound or compounds having a molecular weight of less than 1000. 
     
     
         73 . Use of any of  claims 62  to  72 , wherein said composition comprising a tomato extract or active fraction thereof is selected from the group consisting of juices, pastes, sauces, and soups.