AU3048901A - Dextrose and insulin fluid formulation for intravenous infusion - Google Patents

Description

WO 01/35943 PCT/INOO/00110 DEXTROSE AND INSULIN FLUID FORMULATION FOR INTRAVENOUS INFUSION. BY DR.H.T.GANGAL, HOSUR, HUBLI. 580021. KARNATAKA. INDIA. Patients receive intravenous fluids in the form of nutrients minerals vitamins antibiotics and other life saving drugs in a number of clinical conditions. It is also reliable and effective means of providing them with predictable effects and minimum of inconvenience. This may be the only means of treatment feasible in many occasions as a measure of resuscitative procedure to revive the patients from critically ill state to a state of survival and back to normal life. The presently available fluids are inadequate in all aspect except the water content of the need of the patient. They are hypotonic in effect even though they are isotonic when used in critical conditions. The author has been feeling, the needs of the patients under such circumstances by the presently infused fluids are hardly met. Thus putting the patient in a state of disadvantage to face the situation and to recover back to normal. Preamble With the development of science the desires and expectations of the patients keep on improving in terms of better results, at less cost, effort, and loss of working time, in previously treatable cases. And revival and prolongation of life when earlier they were not possible. Much has been achieved in these directions in medical science. As part of the treatment even today the intravenous infusions consist mainly water dextrose electrolytes. Subsequently the same route has been utilised for administration of antibiotics, proteins and lipid solutions along with many other soluble materials needed in particular instances. The commonly used solutions are in packing of 500 ml in the form of 1. 5% Dextrose 2. 0.9% NaCl solutions 3. Ringers lactate solutions etc. All these have been used, as basic fluids when patient needed administration of therapeutic fluids and other ingredients. In certain special circumstances, fluids like 1. 10% Dextrose 2. 10% Dextrose in normal saline (0.9%) 3. 20-25% Dextrose 4. Dialysis fluids 5. Blood and blood components 6. Low Molecular Dextrans 7. Mannitol 8. Bulk form antibiotics and 9. Many other drugs have been used today. Now, it appears evident that, we have been providing insufficient and inadequate calories; from limited sources of these needed calories by way of energy substrates. So also the electrolytes, vitamins and other needed elements. This late awareness of inadequate knowledge on the needs of the treatment of stress, shock, and critical conditions has resulted in many centres to put up added attention and efforts to study and WO 01/35943 PCT/INOO/00110 evaluate the effects. This effort has lead to more specific and allied in formations to be available, stressing the need to restore homeostasis towards normal, by restoring tissue perfusion and acid base balance towards normal. This will enable to improve the condition, to revive and restore normalcy, as has been stressed by the investigator. The presently available fluids are 1. Unable to meet the calorie need of the patient. These needed calories require to originate from dextrose, aminoacids, and fats. 2. Unable to meet the electrolytes required by the patient, in terms of variety and quantity, 3. The body is unable to utilise, the energy substrate and electrolytes available, in view of high levels of catacholamines, along with qualitative and quantitative deficiency of insulin, and disturbed hormonal levels. All these effects lead to a state of catabolism. Their consequential effects on the body are aptly described as a state of autocannibalism. We need to stop or prevent this from happening or continuing. This emphasises, the infusions to provide the needs of the body in terms of, calorie, electrolytes, vitamins and other essentials to enable and utilise to treat, improve, revive and restore normalcy. Prophylactic measures on this line of approach in expected situations like major operative procedures enable one to minimise the risks of the procedure considerably. The fluids needed are broadly categorised for use to suit the various situations. They are to be in packing of 500 ml for calculations .The following abbreviations are used to denote the fluid and their possible place of use. G - Ganual, N- Non diabetic, D - Diabetic, E - Electrolytes, H - Heparin, V - Vitamins, I - Insulin, where supplemental Potassium is added they are marked as K. PL - Plain / Soluble bovine insulin or Potentially equivalent Human insulin preferred. Dext - Dextrose. A.E - Actual electrolytes to replace the Extra cellular electrolytes, A.M - Actual electrolytes needed in Maintenance solutions as are presently available, to be taken as 500 ml packing for values of their contents. The fluids needed to treat patients who are said to be non-diabetic, as are known to day, are called GN 1 containing the ingredients as stated in the abbreviated text form in the columns Sr.no GN 1 1 10%Dext + 0.9%Nacl + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 16 LU PL Insulin 1K 10%Dext + 0.9%Nacl + 0.6875gm Cal Glu + 20 mEq Kcl (1.50 gm) + 16 LU PL Insulin 2 10%Dext in A.E Sol + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 16 IU PL Insulin 3 10%Dext in A.M.Sol + 0.6875gm Cal Giu + 10 mEq Kcl (0.75 gm) + 16 IU PL Insulin 4 15%Dext + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 24 IU PL Insulin 5 20%Dext + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 32 IU PL Insulin 5K 20%Dext + 0.6875gm Cal Glu + 20 mEq Kcl (1.50 gm) + 32 IU PL Insulin There could be / are occasions where electrolyte requirements could be higher. In such situation WO 01/35943 PCT/INOO/00110 we need to provide higher doses in the form GN 2 - E Group of solutions Sr.no GN2-E 1 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 16 IU PL Insulin 1K 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 20 mEq Kci (1.500 gm) + 16 IU PL Insulin 2 10%Dext in A.E Sol + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 16 IU PL Insulin 3 10%Dext in A.M.Sol + 1.032 gm Cal Glu + 10 mEq Kcl (0.750 gm) + 16 IU PL Insulin 4 15%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 24 LU PL Insulin 5 20%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 32 IU PL Insulin 5K 20%Dext + 1.032 gm Cal Giu + 20 mEq Kcl (1.500 gm) + 32 LU PL Insulin L There could be / are occasions where Heparin may be required and can be added to GN 1 Group of Solutions. These fluids thus formed could be called as GN3 - H Group of Solutions Sr.no GN 3- H 1 10%Dext + 0.9%Nacl + 0.6875 gmCal Glu + 10 mEq Kcl (0.75 gm) + 16 IU PI Insulin 1000 IU Heparin 1K 10%Dext + 0.9%Nacl + 0.6875gm Cal Glu + 20 mEq Kcl (1.50 gm) + 16 IU PI Insulin 1000 IU Heparin 2 10%Dext in A.E Sol + 0.6875 gmCal Gin + 10 mEq Kcl (0.75 gm) + 16 IU Pl Insulin 1000 LU Heparin 3 10%Dext in A.M.Sol + 0.6875 gmCal Glu + 10 mEq Kcl (0.75 gm) + 16 LU PI Insulin 1000 IU Heparin 4 15%Dext + 0.6875 gmCal Glu + 10 mEq Kcl (0.75 gm) + 24 LU P Insulin 1000 IU Heparin 5 20%Dex + 0.6875 gmCal Glu + 10 mEq Kcl (0.75 gm) + 32 LU PI Insulin 1000 LU Heparin 5K 20%Dext + 0.6875gm Cal Glu + 20 m1Eq Kcl (1.50 gm) + 32 IU PI Insulin 1000 IU Heparin There could be / are occasions where Vitamins may be required and can be added to GN 1 Group of Solutions. These fluids thus formed could be called as GN 4 - V Group of Solutions Sr.no GN 4-V 1 10%Dext + 0.9%Nacl + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 16 IU P1 Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I WO 01/35943 PCT/INOO/00110 1K 10%Dext + 0.9%Nacl + 0.6875gm Cal Gin + 20 mEq Kcl (1.50 gm) + 16 IU P Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 2 10%Dext in A.E Sol + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 16 IU P Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 3 10%Dext in A.M.Sol + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 16 IU P Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 4 15%Dext + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 24 IU P Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 5 20%Dext + 0.6875gm Cal Glu + 10 mEq Kcl (0.75 gm) + 32 IU P Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 5K 20%Dext + 0.6875gm Cal Gin + 20 mEq Kcl (1.50 gm) + 32 IU P Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I There could be / are occasions where electrolyte requirements could be higher along with the need of Heparin. In such situation we need to provide these doses in the form of GN 5 - EH group of solutions. Sr.no GN 5- EH 1 10%Dext + 0.9%Nacl + 1.032gm Cal Glu + 15 mEq Kcl (1.125 gm) + 16 IU PL Insulin 1000 IU Heparin 1K 10%Dext + 0.9%Nacl + 1.032gm Cal Glu + 20 mEq Kel (1.500 gm) + 16 IU PL Insulin 1000 IU Heparin 2 10%Dext in A.E Sol + 1.032gm Cal Glu + 15 mEq Kcl (1.125 gm) + 16 LU PL Insulin 1000 IU Heparin 3 10%Dext in A.M.Sol + 1.032gm Cal Glu + 10 mEq Kcl (0.750 gm) + 16 IU PL Insulin 1000 IU Heparin 4 15%Dext + 1.032gm Cal Glu + 15 mEq Kcl (1.125 gm) + 24 IU PL Insulin 1000 IU Heparin 5 20%Dext + 1.032gm Cal Gin + 15 mEq Kcl (1.125 gm) + 32 LU PL Insulin 1000 IU Heparin 5K 20%Dext + 1.032gm Cal Glu + 20 mEq Kcl (1.50 gm) + 32 IU PL Insulin 1000 IU Heparin There could be / are occasions where requirements could be the need of additional electrolytes and also Vitamin along with GN 1 Solutions. In such situation we need to provide these doses in the form of GN 6 - EV aroup of solutions WO 01/35943 PCT/INOO/00110 Sr.no GN6-EV 1 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 16 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1K 10%Dext + 0.9%Nacl + 1.032gm Cal Glu + 20 mEq Kcl (1.500 gm) + 16 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 2 10%Dext in A.E Sol + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 16 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 3 10%Dext in A.M.Sol + 1.032 gm Cal Glu + 10 mEq Kcl (0.750 gm) + 16 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 4 15%Dext + 1.032 gm C al Glu + 15 mEq Kcl (1.125 gm) + 24 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 5 20%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 32 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 5K 20%Dext + 1.032gm Cal Glu + 20 mnEq Kcl (1.500 gm)+ 32 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I There could be / are occasions where requirements could be the need of, Heparin and also Vitamins along with GN 1 Solutions. In such situation we need to provide these doses in the form of GN 7 - HV group of solutions Sr. no GN 7 - HV 1 10%Dext + 0.9%Nacl + 0.6875 gm Cal Gin + 10 mEq Kcl (0.75 gm) + 16 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 1K 10%Dext + 0.9%Nacl + 0.6875 gm Cal Glu + 20 mEq Kcl (1.50 gm) + 16 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, 1 1000 IU Heparin 2 10%Dext in A.E Sol + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 16 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, 1 1000 LU Heparin 3 10%Dext in A.M.Sol + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 16 LU PL Insulin. Vitamins A, D, E, B-comp,C, CC, DL-M, 1 1000 IU Heparin 4 15%Dext + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm)+ 24 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 5 20%Dext + 0.6875 gm Cal Glu + 10 mEq Kel (0.75 gm) + 32 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 5K 20%Dext + 0.6875gm Cal Glu + 20 mEq Kcl (1.50 gm) + 32 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin WO 01/35943 PCT/INOO/00110 There could be / are occasions where requirements could be the need of higher amounts of Electrolytes, Heparin and also Vitamins along with GN 1 Solutions. In such situation we need to provide these doses in the form of GN8 - EHV group of solutions Sr. no GN 8- EHV 1 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 16 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 LU Heparin 1K 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 20 mEq Kcl (1.500 gm) + 16 1U PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, 1 1000 IU Heparin 2 10%Dext in A.E Sol + 1.032 gm Cal Gin + 15 mEq Kcl (1.125 gm) + 16 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 3 10%Dext in A.M.Sol + 1.032 gin Cal Glu + 10 mEq Kcl (0.750 gm) + 16 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 LU Heparin 4 15%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 24 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 5 20%Dext + 1.032 gm Cal Gin + 15 mEq Kcl (1.125 gm) + 32 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, 1 1000 IU Heparin 5K 20%Dext + 1.032 gm Cal Glu + 20 mEq Kel (1.500 gm) + 32 IU PLInsulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 LU Heparin The use of GN 1 fluids in treating manifest diabetic cases, the need of insulin will be definitely more. Hence additional quantity of insulin is added to this group of solutions called GD 9. Sr.no GD 9 1 10%Dext + 0. 9%Nacl + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 20 IU PL Insulin 1K 10%Dext + 0.9%Nacl + 0.6875 gm Cal Glu + 20 mEq Kcl (1.50 gm) + 20 IU PL Insulin 2 10%Dext in A.E Sol + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm)+ 20 LU PL Insulin 3 10%Dext in A.M.Sol + 0.6875 gm Cal Gin + 10 mEq Kcl (0.75 gm) + 20 LU PL Insulin 4 15%Dext + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) +30 LU PL Insulin 5 20%Dext + 0.6875 gm Cal Glu + 10 nEq Kcl (0.75 gm)+ 40 IU PL Insulin 5K 20%Dext + 0.6875 gm Cal Glu + 20 mEq Kcl (1.50 gm)+ 40 IU PL Insulin There could be/are occasions where electrolyte requirements could be higher than in GD 9 solutions In such situation we need to provide higher doses to provide tenth group solutions called GD 1.-E Sr. no GD 10 - E WO 01/35943 PCT/IN00/00110 1 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 20 IU PL Insulin 1K 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 20 mEq Kcl (1.500 gm) + 20 IU PL Insulin 2 10%Dext in A.E Sol + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 20 IU PL Insulin 3 10%Dext in A.M.Sol + 1.032 gm Cal Glu + 10 mEq Kcl (0.750 gm) + 20 IU PL Insulin 4 15%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 30 IU PL Insulin 5 20%Dext + 1.032 gm Cal Gin + 15 mEq Kcl (1.125 gm) + 40 LU PL Insulin 5K 20%Dext + 1.032 gm Cal Gin + 20 mEq Kcl (1.500 gm) + 40 IU PL Insulin There could be / are occasions where Heparin may be required and can be added to GD 9 Group of Solutions. These fluids thus formed could be called as GD 11 - H Group of Solutions Sr. no GD 11 - H 1 10%Dext + 0. 9%Nacl + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 20 IU PL Insulin 1000 LU Heparin 1K 10%Dext + 0.9%Nacl + 0.6875 gm Cal Glu + 20 nEq Kcl (1.50 gm) + 20 LU PL Insulin 1000 IU Heparin 2 10%Dext in A.E Sol + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 20 LU PL Insulin 1000 LU Heparin 3 10%Dext in A.M.Sol + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 20 IU PL Insulin 1000 IU Heparin 4 15%Dext + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 30 LU PL Insulin 1000 IU Heparin 5 20%Dext + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 40 LU PL Insulin 1000 IU Heparin 5K 20%Dext + 0.6875 gm Cal Glu + 20 mEq Kcl (1.50 gm) + 40 IU PL Insulin 1000 IU Heparin There could be / are occasions where Vitamins may be required and can be added to GD 9 Group of Solutions. These fluids thus formed could be called as GD 12 - V Group of Solutions Sr. no GD 12 - V I 10%Dex + 0.9%Nacl + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 20 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1K 10%Dex + 0.9%Nacl + 0.6875 gm Cal Glu + 20 mEq Kcl (1.50 gm) + 20 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 2 10%Dex in A.E Sol + 0.6875 gm Cal GIu + 10 mEq Kel (0.75 gm) + 20 IU PL Insulin WO 01/35943 PCT/INOO/00110 Vitamins A, D, E, B-comp,C, CC, DL-M, I 3 10%Dex in A.M.Sol + 0.6875 gm Cal Gin + 10 mEq Kcl (0.75 gm) + 20 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 4 15%Dex + 0.6875 gm Cal Glu + 10 mEq Kcl (0.75 gm) + 30 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 5 20%Dex + 0.6875 gm Cal Gin + 10 mEq Kcl (0.75 gm) + 40 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 5K 20%Dex + 0.6875 gm Cal Giu + 20 mEq Kcl (1.50 gm) + 40 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I There could be / are occasions where electrolyte requirements could be higher along with the need of Heparin. In such situation we need to provide these doses in the form of GD 13 - EH group of solutions Sr.no GD 13 - EH 1 10%Dext + 0.9%NacI + 1.032 gm Cal Gin + 15 mEq Kcl (1.125 gm) + 20 IU PL Insulin 1000 IU of Heparin 1K 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 20 mEq Kcl (1.500 gm) + 20 IU PL Insulin 1000 LU of Heparin 2 10%Dext in A.E Sol + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 20 LU PL Insulin 1000 LU of Heparin 3 10%Dext in A.M.Sol + 1.032 gm Cal Glu + 10 mEq Kcl (0.750 gm) + 20 IU PL Insulin 1000 LU of Heparin 4 15%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 30 IU PL Insulin 1000 IU of Heparin 5 20%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 40 LU PL Insulin 1000 IU of Heparin 5K 20%Dext + 1.032 gm Cal Glu+ 20 mEq Kcl (1.500 gm) + 40 IU PL Insulin 1000 IU of Heparin The GD 9 solutions are supplemented with Electrolytes and Vitamins to gain GD 14 - EV solutions. Sr. no GD 14 - E V 1 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 20 IU PL Insulin Vitamins A, D, E, B-comp, C, CC, DL-M, I 1K 10%Dext + 0.9%Nacl + 1.032 gm Cal Glu + 20 mEq Kcl (1.500 gm) + 20 LU PL Insulin Vitamins A, D, E, B-comp, C, CC, DL-M, I WO 01/35943 PCT/INOO/00110 2 10%Dext in A.E Sol + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 20 IU PL Insulin Vitamins A, D, E, B-comp, C, CC, DL-M, I 3 10%Dext in A.M.Sol + 1.032 gm Cal Glu + 10 mEq Kel (0.750 gm) + 20 IU PL Insulin Vitamins A, D, E, B-comp, C, CC, DL-M, I 4 15%Dext + 1.032 gm Cal Glu + 15 mEq Kcl (1.125 gm) + 30 IU PL Insulin Vitamins A, D, E, B-comp, C, CC, DL-M, I 5 20%Dext + 1.032 gm Cal Glu + 15 mEq Kel (1.125 gm) + 40 LU PL Insulin Vitamins A, D, E, B-comp, C, CC, DL-M, I 5K 20%Dext + 1.032 gm Cal Glu + 20 mEq Kcl (1.500 gm) + 40 IU PL Insulin Vitamins A, D, E, B-comp, C, CC, DL-M, I The GD 9 group of fluids is supplemented with Heparin and Vitamins. They provide GD 15 - H V group of solutions. Sr. no GD 15 - H V 1 10%Dext + 0.9%Nacl + 0.6875 gm CalGlu + 10 mEq Kcl (0.75 gm) + 20 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU of Heparin 1K 10%Dext + 0.9%Nacl + 0.6875 gm CalGlu + 20 mEq Kcl (1.50 gm)+ 20 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, 1 1000 IU of Heparin 2 10%Dext in A.E Sol + 0.6875 gm CalGlu + 10 mEq Kcl (0.75 gm) + 20 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU of Heparin 3 10%Dext in A.M.Sol + 0.6875 gm CaiGlu + 10 mEq Kcl (0.75 gm) + 20 LU PL Insulin. Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 LU of Heparin 4 15%Dext + 0.6875 gm CalGlu + 10 mEq Kcl (0.75 gm)+ 30 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU of Heparin 5 20%Dext + 0.6875 gm CalGlu + 10 mEq Kel (0.75 gm) + 40 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU of Heparin 5K 20%Dext + 0.6875 gm CalGlu + 20 mEq Kcl (1.50 gm)+ 40 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 LU of Heparin The GD 9 combination fluids are supplemented with Electrolytes, Heparin and Vitamins. These fluids form the GD 16 - EHV. Group of solutions Sr. no GD 16 - E HV 1 10%Dext + 0.9%Nacl + 1.032 gmCal Glu + 15 mEq Kcl (1.125 gm) + 20 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 1K 10%Dext + 0.9%Nacl + 1.032 gmCal Glu + 20 mEq Kcl (1.500 gm) + 20 IU PL Insulin WO 01/35943 PCT/INOO/00110 Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 2 10%Dext in A.E Sol + 1.032 gmCal Glu + 15 mEq Kcl (1.125 gm) + 20 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 3 10%Dext in A.M.Sol + 1.032 gmCal Glu + 10 mEq Kcl (0.750 gm) + 20 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 4 15%Dext + 1.032 gmCal Glu + 15 mEq Kcl (1.125 gm) + 30 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin 5 20%Dext + 1.032 gmCal Glu + 15 mEq Kcl (1.125 gm) + 40 IU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 LU Heparin 5K 20%Dext + 1.032 gmCal Gin + 20 mEq Kcl (1.500 gm) + 40 LU PL Insulin Vitamins A, D, E, B-comp,C, CC, DL-M, I 1000 IU Heparin Clarification information The tables below provide information about A.E, the Actual electrolytes in Extra cellular replacement and A.M, Actual electrolytes in Maintenance solutions as are available. The values expressed in the table against each item is the actual content of the ingredients in 100 ml of each fluids as are in use today. Sr. no Each 100ml contains A.E A.M 1 Sodium Acetate .P 0. 64 gm 0. 28 gm 2 Sodium Chloride I.P 0. 50 gm 91 mg 3 Potassium Chloride IP 75 mg 0. 15 gm 4 Sodium Citrate IP 75 mg 5 Calcium Chloride IP 52 mg 6 Magnesium Chloride I.P 31 mg 7 Sodium Meta bi Sulphite IP 20 mg 21 mg 8 Dibasic Potassium Phosphate. I.P - 0. 13 gm Bicarbonate Precursor - Osmolarity (A-E Solutions) Approx 570 Calculated Osmolarity (A-M Solutions) Approx 400 Concentration of Electrolytes in (mEq / L) Sr. no Electrolytes in (mEq / L) A.E A.M 9 Sodium 140 40 10 Chloride 103 40 11 Acetates 47 20 10 WO 01/35943 PCTINOO/00110 12 Potassium 10 35 13 Citrates 8 0 14 Calcium 5 0 15 Magnesium 3 0 16 Phosphate 0 15 17 Total Cations - 75 18 Total Anions - 75 The Vitamins added per 500 ml of fluids. Sr. no Vitamins Qty 1 Vitamin A, I.P. (as Palmitate) 4000 LU 2 Thiamine Hydrochloride I.P 100 mg 3 Pyridoxine Hydrochloride LP 10 mg 4 Riboflavin Sodium Phosphate I.P 10 mg 5 Nicotinamide I.P 100 mg 6 D. Pantothenol I.P 20 mg 7 Vitamin B12. I.P 15 mcg 8 Ascorbic acid. I.P 200 mg 9 Cholecalciferol I.P 300 IU 10 Alpha Tocoferil Acetate I.P 5 mg 11 Choline Chloride 10 mg 12 DIMethionine 10 mg 13 Inositol 6 mg Oil Soluble Vitamins A, D, E, are made water soluble to be used here. With these improved formulations, it has been possible to meet the largely needed requirements under various types of critical clinical conditions, as can be rationalised to day. One should appreciate; these formulations may be able to meet the needed requirements. They will enable us to standardise the approach, and give scope in future a better way to improve further the formulations. Thus will enabling us to gain still further occasion to improve the formulations to attain better results within scope of the appended claims in formulations. We may also gain better and larger scope of their use in various other conditions. The formulations consist of the following and other ingredients mentioned in the above clarifications and in the text. 1. Water: Water is the main and the essential natural component of the body, and is also the main vehicle / media through which the body's circulation is maintained. This makes it possible the essentials of life 11 WO 01/35943 PCT/INOO/00110 -and function are made available from the body to the cell level and receives back the wastes from the cell level to the organ to be eliminated out of the body. It helps to mentain physiological state in and around the body, congenial to sustain normal life. The volume of the water needed by the body varies with the functional level, the problems faced and the environment. Accordingly the volume of fluid needed to be infused, to balance the need and the output and also to maintain an effective circulation, are required into consideration to asses. 2. Dextrose: A major source of energy out of all other essential energy substrates. A must for living and sustaining life. Dextrose in the form of 5% as an isotonic solution has been the main stay of intravenous infusion in all forms of conditions where infusion forms the treatment as well as a resuscitative measure. In states of stress, shock, and critical conditions, this isotonic solution is now understood to have hypotonic solution effect. This type of fluids, are likely to cause enormous harmful effects. Where as the fluids we use in hypertonic form enable us to provide needed higher calories along with insulin, and also avoid effects of hypotonic solutions. Normally it forms the main source of energy to be supplemented by amino acids, and emulsified fat solutions. This helps to meet the needs of essential amino acids, and also fats; along with it enables to prevent the bad and rebound effects of prolonged use of carbohydrates alone. This results in accumulation of acidic components and triggering of catacholamine response, indeed an unwanted response at an odd occasion to result in further effects to an already critical condition. Here, 10%, 15%, 20%, are used to provide higher amount of dextrose along with insulin, electrolytes, vitamins, and Heparin to meet the high levels of metabolism. This is likely to avoid auto cannibalism and its consequent outcome of survival. 3. Na: Sodium chloride forms a major and a main electrolyte. It is also called the second pump to maintain the circulation. Sodium Chloride: 0.9% Nacl is an isotonic solution, commonly used as such or in combination with Dextrose solutions. It is one of the main electrolyte, the body needs. It is mainly an extra cellular electrolyte with a small intracellular component, having a reciprocal gradient relation with K ion responding to any effective agents. The intake and output needs to be balanced. The body contains a large amount, nearing around 5000 mEq of Na, with an average need of, 80 - 100, mEq / Day. This is mostly lost in the urine. In the normal individual, on one hand there is a large reserve, on the other hand there is an excellent mechanism to conserve it by normal functioning kidney. This can result in bringing urinary loss of Na to near zero, in the absence of intake of Na. Still large fluctuations do occur with resultant serious problems. Hence it needs to be managed properly to retain homeostasis 4. Ca: Calcium similarly forms a major cation component of the body, having role to play in homeostasis, membrane potentials, inter cellular junctions and cell functions. Calcium: Calcium forms around 2% of the bodyweight. Ninety nine % of it is in the form of bone. Part of it is constantly changing to contribute to the extra-cellular component. This is under the influence of

II

WO 01/35943 PCT/IN00/00110 simple ion exchange. Paratharmone, Vit D, Corticosteroids cause disturbances in Calcium content. Any variations in the extra-cellular component affect the homeostasis. This in turn results in deranged cellular functions. Average Indian diet may contain as low as 0.2 Gms as against the daily need of 0.5 to 0.6 gm on an average. The needs are higher in later terms of pregnancy and lactation, thus needing up to around 1 gram of Calcium a day. Intracellular Ca regulates cell metabolism, it's function and inter junction permeability. With normally functioning kidneys, 99% of the Ca gets reabsorbed from the tubules. Urinary Ca excretion increases with hypercalcaemia of any cause, metabolic acidosis and use of cortisones. Ca is an important component of the cell membrane and competes with Na. Raised Ca, in blood increases the threshold for contraction and low Ca leads to tetany. Ca also plays role in coagulation of blood, coupling mechanism between excitation and contraction of muscles, and secretary mechanism of Insulin. 5. K: Potassium mainly an intracellular electrolyte having a significant role to play in cell membrane potentials and cell functions. Potassium chloride: KCl solution is available for intravenous use, needs to be diluted considerably to use. Normally there is about 3500 mEq of Potassium in the body, of which 98%is intracellular and hardly 2% is in extra-cellular compartment. This small part of the Potassium plays a major role in the functioning of the smooth, skeletal, and cardiac muscles. As a result any variations that occur in its level can certainly cause considerable problems. Seventy-five percent of the Potassium is found in the skeletal muscles. Normally on an average the body needs around 50 to 80 mEq of Potassium per day. The main route of loss is through normally functioning kidney. The minimum that is lost through urine could be 20 mEq even in the absence of Potassium intake. In view of the high quantity of Potassium is in intracellular compartment any injury to the organs is bound to increase the extra-cellular Potassium. It is to a certain extent dependent on the level of Sodium, other hormones and diuretics. Its movements / transfer is related to metabolism. There are occasions where intracellular Potassium deficiency may be present although the plasma level is normal; such situations need careful evaluation than casual look. 6. Other electrolytes: As are included in the A.E, extra cellular electrolyte replacement component and A.M, electrolyte maintenance replacement component solutions are also essential to the body's function and are required to be maintained in balance. All these have been used in clinical application. 7. Insulin: Insulin is an essential hormone required in the process of metabolism of carbohydrates, proteins, and fats. Involving almost all organs in the body. It is now fairly well established, in clinical states needing intravenous infusions, there is qualitative and quantitative deficiency of insulin. 8. Heparin: It is a naturally occurring substance, not occurring in blood to a measurable extent, prevents blood coagulation. It plays significant role in cases of trauma induced on any account.

WO 01/35943 PCT/IN00/00110 Blood coagulation is essentially a series of enzymatic reactions involving a number of plasma proteins. Many of these are present only in traces. Within an intact healthy circulatory system these enzymes, for the most part, are in an inactive form, when the blood is shed on wettable surfaces, a series of auto catalytic enzymatic reaction is initiated, this is a process of more complex and confused in results, interpretations, and opinions. Heparin when added as a therapeutic agent, it acts at a number of sites along the chain of reaction. Its probable initial, action is to prevent the development of thromboplastin activity. Heparin has immediate action on the coagulation system. It is a naturally occurring sulfonated polysaccharide with strong anticoagulant action. It is rapidly inactivated and removed from the circulation. It is difficult to maintain therapeutic level in the blood while avoiding the danger from bleeding. Here it is used to prevent likely initiation of early thromboembolic phenomenon. In the present situation medical science is not as exact as mathematics and it may not be so forever. Life science is so complex, and every effort, to understand, evaluate, or treat, involves, time, money, risk and need of invasive procedures, with added risks. 9. Vitamins: Fat and water-soluble vitamins are organic compounds, forming as components or cofactors for enzymes concerned with metabolism of carbohydrates, fats, and proteins. Most of the vitamins are acquired from dietary sources. Very few to a small extent are synthesised in the body. B. Group vitamins act, as essential co-enzymes required as intermediary in the metabolism. Dietary vitamins need to be converted to its co-enzyme form in order to be useful. It is also noted these vitamins are interdependent on their metabolism and utilisation. In the absence of sources of supply, use of various drugs affecting their metabolism, that too under circumstances of raised metabolic state, there, does occur an occasion to provide these needed Vitamins in the form of intravenous administration. These Vitamins are classified, as Fat Soluble Vitamins, A D.E.K are stored in the body. Water Soluble Vitamins, B Group & C are not stored and any excess is rapidly excreted in the urine. They are not toxic. And tend not to cause interaction with drugs. This likely Vitamin deficiency occurring during total parenteral nutrition, are attended by providing as follows. Vitamin A: -Daily dose of around 10,000 to 20,000 I.U in the form of made as water soluble could be essential to maintain the integrity of the epithelial cells, synthesis of glucocortcoids, cholesterol, and for somatic growth, upper respiratory tract epithelium. Vitamin B 1 : - It is mainly concerned with Carbohydrate metabolism. IV / IM administration of large doses may cause anaphylactic shock and interfere with action of other B vitamins.

B

3 - Nicotinic acid is required in Protein metabolism, necessary in respiration WO 01/35943 PCTIINOO/00110

B

6 - Indirectly affects carbohydrate metabolism, directly the catacholamines, gamma-amino butyric acid, etc., BT - is involved in fundamental biological reactions.

B

12 . is necessary in maintenance of function of the nervous system and conduction mechanism. C: - Concerned with cellular respiration / oxidation-reduction reactions, and formation of collagen, intercellular matrix development of cartilage, wound healing, carbohydrate metabolism. Vitamin D: - Facilitates interdepartmental metabolism between vitamins, and maintains Ca. homeostasis. It is quite important in the acute conditions, like mobilisation of insulin, coupling mechanism of excitation and contraction mechanism of muscles. These have some relevance to diabetes normal organ function and essential hypertension. E: - Alpha Tocopheryl Acetate is said to be essential to maintain integrity and stability of biological membranes, normal structure and function of the nervous system and is mostly used on an empirical base. It is known to be antioxidant. Choline Chloride is akin to B group of Vitamins but synthesised in the human body. It plays an important role as a structural component of tissues and in biological methilation reactions. It is a precursor of acetylcholine, and some hormones. Its biogenesis is universal in nature. It helps to spare amino acids in protein synthesis. It prevents fatty infiltration of liver, a hypertropic agent; average estimated consumption appears to be around 500 to 900 mgm/a day. DL - Methionine: - is sulphur containing aminoacid and inseparable dietary component. Methionine has lipotropic action, and is considered as useful adjutant of treatment of liver diseases. It enhances synthesis of glutathione, necessary for detoxification of toxic metabolites of paracetamol. Average needs are around 200 to 500 mgm. Inosital: - occurs in nearly all plant, and animal cell, suggesting it to be an essential cell constituent. It is found to be a constituent of an amylase enzyme system. To a certain extent it is synthesised by the intestinal flora. It possesses weak lipotropic activity prevents fatty liver. It could be beneficial in diabetic neuropathy. Stress, trauma, shock, critical conditions, sepsis, surgery increase the catabolic rate. This increased catabolism is a self-destructive response to the above stated illnesses. It is termed as auto cannibalism needing everyone's attention to prevent it occurring. The developments in medical sciences appear to have been based mostly on the outcome of interested individuals efforts. There has been no systematic developmental effort to study life science, as it stands smaller priority, in the Government and personal levels. Hence allocation of funds in comparison with defence, industry etc is very meagre. In such circumstances the evaluations are difficult. Presently adopted methods of treatment are largely based on the individual knowledge, and capability to evaluate the condition he is handling. Thus giving large scope for variations and the resultant outcomes.

WO 01/35943 PCT/INOO/00110 On the background of the experience in the experimental surgery in developing open heart surgery and handling critically ill patients, major trauma patients, the concept adopted by me and resultant comparatively better outcomes led me to continue the work and peruse to gain further information on the line. I continued to try the concept in conditions where the senior colleagues could not expect any hope (with appreciable good results), convinced me, the approach stands better scope in the present situation. With more and more information now available, the scope of use of my concept has enlarged and the results have proved its worthiness to be pursued. It needs fair variations with the fundamental concept remaining to be the backbone in all its variant approach in different clinical pictures. I feel stress, trauma, shock critical conditions; surgery infections cause state of disturbed neuro hormonal response resulting in changed hormonal catacholamine levels, homeostatic conditions, altered level of defence mechanism and metabolism. All needs to be attended, to provide proper physiological response to restore normalcy and recovery. This needs the approach to be well balanced, gradual, predictable and reasonable, to gain near natural normal life, without the need of prolonged therapy assisted sustenance of life. 1) I also feel every individual is potentially diabetic, hypertensive more so under states of stress and allied situations is now corroborated by quite a few. 2) There is a raised metabolism under states of stress & critical condition leading to auto cannibalism, a worst situation leading to multiple organ dysfunction syndromes. As a preventive measure to minimise such occurrences, I use these fluids, in 1) Stress - Primary Hypertension Angina pectoris. 2) Shock, a) Multiple traumatic injuries. b) Perforative peritonitis c) Pancreatitis d) Major operative procedures e) Major vascular surgeries. Like thrombo-end arterectomies Meso-caval anatomises in portal hypertension etc. 3) Cirrhosis of liver 4) Scorpion strings, Snake bites 5) Bacterial resistant infections - Septic shock 6) In conditions a) Coronary Artery diseases b) Myocardial Infarcts c) Following Cardio-Vascular Surgeries 7) Adult Respiratory distress Syndromes. / Multi-organ Dysfunction Syndrome 16 WO 01/35943 PCT/INOO/00110 8) In the treatment of Cancer 9) Poly - Cystic Kidney 10) Alzheimer's disease & many other clinical conditions associated with critical situations. 11) These fluids possibly by their concurrent use in conditions like HIV and Australian Antigen Virus infection rabies, and tetanus may provide better results by restoring the cell and organ environment, to a near normal level, and assist the defence mechanism of the body they have beneficial effects on the cell membrane. 1'"

Claims (25)

1. Water, the main media, 500-ml.

2. Dextrose 10% to 20%

3. Insulin 0.32 to 0.40. I.U, /Gm of Dextrose

4. Sodium Chloride (NaCI) 0 to 4.5Gms

5. Calcium Gluconate 0.6875 to 1.375Gms

6. Potassium Chloride (KCI) 0 to 1.5 Gms

7. Sodium Acetate 0 to 3.2 Gms

8. Sodium Citrate 0 to 375 mgm

9. Calcium Chloride 0 to 260 mgm

10. Magnesium chloride 0 to 155 mgm

11. Sodium Meta-Bisulphite 0 to 105 mgm

12. Dibasic Potassium Phosphate 0 to 0.65 Gms C. Vitamins I.P.

13. Vitamin A 0 to 4000 I U

14. Thiamine Hydrochloride I.P. 0 to 50 mg

15. Pyridoxine Hydrochloride I.P. 0 to 6 mg

16. Riboflavin Sodium Phosphate 0 to 6

17. Nicotinamide I.P. 0 to 50 mg

18. D.Pantothenol I.P. 0 to 10 mg

19. Vitamin B12 .P 0 to 15 mcg

20. Ascorbic acid IP 0 to 200 mg

21. Cholecalciferol I.p. 0 to 300 LU

22 Alpha Tocoferil Acetate I.P. 0 to 2 mg

23. Choline chloride 0 to 5 mg

24. Di-methionine 0 to 5 mg

25. Inositol 0 to 3 mg D. Heparin 0 to 1000 LU The above claims A, B, C and D enable me to claim further that these fluids are effective in treating the conditions stated above. The above formulations have proved effective all along for use on immediate use of their formulation. In case there is going to be problem of stability of the formulation, they will necessarily be put in combination (separate) packages suitable for mixing immediately prior to its use. 1 o WO 01/35943 PCT/INOO/00110 ABSTRACT DEXTROSE AND INSULIN FLUID FORMULATION FOR INTRAVENOUS INFUSION. BY DR.H.T.GANGAL, HOSUR, HUBLL 580021. KARNATAKA. INDIA. Patients receive intravenous fluids in the form of, fluid, media, nutrients minerals vitamins antibiotics and other life saving drugs in a number of clinical conditions. It is also reliable and effective means of providing them predictable effects with minimum of inconvenience. This may be the only means of treatment feasible on many occasions as a measure of resuscitative procedure to revive the patients from critically ill state to a state of survival and back to normal life. The presently available fluids are inadequate in all aspect except the water content of the need of the patient. They are hypotonic in effect even though they are isotonic when used in critical conditions. The author has been feeling, the needs of the patients under such circumstances by the presently infused fluids are hardly met. Thus putting the patient in a state of disadvantage to face the situation and to recover back to normal. With the development of science the desires and expectations of the patients keep on improving in terms of better results, at less cost, effort and loss of working time, in previously treatable cases. And revival and prolongation of life when earlier they were not possible. Much has been achieved in these directions in medical science. As part of the treatment even today the intravenous infusions consist mainly water dextrose electrolytes. Subsequently the same route has been utilized for administration of antibiotics, Proteins and lipid solutions along with many other soluble materials needed in particular instances. WO 01/35943 PCT/INOO/00110 Sequence listing part of description 1. Introduction of Dextrose And Insulin Fluid Formulation for Intravenous Infusion. 2. Preamble . 3. Background of abbreviations. 4. Formulations in tabulations. 5. Clarification information on A.E., and A.M., Solutions. 6. Osmolarity. 7. Concentration of Electrolytes. 8. Vitamins per 500 ml of fluids. 9. Ingredients like Water, Dextrose. 10. Ingredients like electrolytes. 11. Ingredients like Insulin, and Heparin. 12. Ingredients like vitamins and other precursors. 13. Field of application. 14. Scope of its application in future. In