Insulin Therapies for the Treatment of Diabetes, Diabetes Related Ailments, and/or Diseases or Conditions Other Than Diabetes or Diabetes Related Ailments

• US 20120035105A1
• Filed: 01/08/2010
• Published: 02/09/2012
• Est. Priority Date: 01/09/2009
• Status: Abandoned Application

• Current Assignee: SDG, Inc.
• Original Assignee: SDG, Inc.
• Inventors: Geho, W. Blair, Lau, John R.
• Application Number:
  US13/143,435
• Publication Number:
  US 20120035105A1
• Time in Patent Office: Days
• US Class Current: 514/6.5
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

The present invention includes a pharmaceutical composition comprising HDV insulin or oral HDV insulin, and one or more additional therapeutic agents useful for the treatment of diabetes and diabetes related ailments. The present invention also includes a method of making the pharmaceutical inventions of the application. The present invention further includes methods of treating diabetes and/or diabetes related ailments comprising administering a pharmaceutical composition of the invention to a patient in need thereof. The present invention also includes methods of treating diabetes related ailments comprising administering a pharmaceutical formulation of HDV insulin or a pharmaceutical formulation of oral HDV insulin.

Claims

1. A pharmaceutical composition comprising,

HDV insulin, and

one or more additional therapeutic agents not associated with HDV insulin.

2. The pharmaceutical composition of claim 1, wherein said one or more additional therapeutic agents not associated with HDV insulin are selected from the group consisting of an α

-glucosidase inhibitor, a lipase inhibitor, a sulfonyl urea, a meglitinide, a biguanide, a thiazolidinedione, pramlintide, an incretin mimetic, GLP-1 receptor agonist, a DPP-IV inhibitor, asprin, niacin, a fibrate, a bile acid sequestrant, a cholesterol absorption inhibitor, an omega-3 acid ethyl ester, a secretory phospholipase A2 (“

sPLA2”

) inhibitor, an oligonucleotide-based apolipoprotein B (“

apoB”

) inhibitor, a squalene synthase inhibitor, a statin, a fixed dose combination statin therapy, glucose, glucagon, heparin, an angiotensin II receptor antagonist, an ACE inhibitor, an antidepressant, an anticonvulsant, an opioid, C-peptide, an aldose reductase inhibitor, a pancreatic lipase inhibitor, a serotonin-norepinephrine reuptake inhibitor, a cannabinoid (“

CB1”

) receptor antagonist, a leptin receptor agonist, oxyntomodulin or an oxyntomodulin-derived peptide, peptide tyrosine-tyrosine (PYY), an anti-obesity therapy, an anti-obesity combination therapy, an erectile dysfunction medication, alpha-1-adrenergic receptor blockers, 5-alpha reductase inhibitors, fish oil, plant sterols and stanols, immunosuppressors, SGLT2 inhibitors, 11β

HSD1 inhibitors, adenosine A1 receptor agonists, anti-inflammatory agents, artificial sweeteners, bile acid receptor agonists, CCK receptor antagonists, CCR2 antagonists, diacylglycerol O-acyltransferase homolog 1 (DGAT-1) inhibitors, dopamine receptor agonists, dual-acting peptide-GLP-1 and glucagons receptor agonists, FGF-21 variants, fructose 1,6 bisphosphatase inhibitors, gastrin-releasing peptide (GRP) receptor agonists, GLP-1 analogs, glucagons receptor-antisense, glucokinase activators, glucose-dependent insulinotropic receptor (GDIR/GPR119) agonists, glutamic acid decarboxylases, HM74a agonists, HSP60 peptides, IL-1 antibody (Eli Lilly), insulin-derived peptides, longer acting human GLP-1 analogues, MAbs to CD3, MAbs to glucagon receptors, MAbs to IL-1, MAbs to IL-1β

, permeability inhibitors, plasmid encoding proinsulins, poly(ADP-ribose) polymerase inhibitors, PPAR agonists, PPAR alpha activators, PPAR gamma modulators, PPAR pan agonists, PPARα

/γ

modulators, protein tyrosine phosphatase 1B inhibitor, SGLT1 inhibitors, SIAC (soluble insulin analogue combination, soluble insulin basal analogues, sirtuin (SIRT1) activators, sodium channel blockers, other non-insulin compounds, and combinations thereof.

3. The pharmaceutical composition of claim 2, wherein

said α

-glucosidase inhibitor is selected from the group consisting of acarbose, miglitol, and voglibose;

said lipase inhibitor is orlistat;

said sulfonyl urea is selected from the group consisting of acetohexamide, chlorpropamide, tolbutamide, tolazamide, gliclazide, glyburide, glibenclamide, glipizide glimepiride, and gliquidone;

said meglitinide is selected from mitiglinide, nateglinide, and repaglinide;

said biguanide is selected from the group consisting of metformin, phenformin, and buformin;

said thiazolidinedione is selected from the group consisting of rosiglitazone, pioglitazone, troglitazone, and tesaglitazar;

said incretin mimetic is selected from the group consisting of exenatide and liraglutide;

said DPP-IV inhibitor is selected from the group consisting of sitagliptin, a combination of sitagliptin tin and metformin, vildagliptin, alogliptin, a combination of alogia and metformin, saxagliptin, and a combination of vildagliptin and metformin;

said fibrate is selected from the group consisting of fenofibrate, bezafibrate, and gemfibrozil;

said bile acid sequestrant is selected from the group consisting of colesevelam and cholestyramine;

wherein said cholesterol absorption inhibitor is selected from the group consisting of ezetimibe, FM-VP4, AEGR-733, implitapide and JTT-130;

said omega-3 acid ethyl ester is selected from the group consisting of Omacor™

, Esapent™

, Seacor™

, and Maxepa™

;

said secretory phospholipase A2 inhibitor is selected from the group consisting of S-5920, LY315920, and A-002;

said oligonucleotide-based apolipoprotein B inhibitor is mipomersen sodium;

said statin is selected from the group consisting of mevastatin, lovastatin, simvastatin, pravastatin, fluvastatin, pitavastatin, atorvastatin, cerivastatin, and rosuvastatin;

said squalene synthase inhibitor is lapaquisatat;

said fixed dose combination statin therapy is selected from the group consisting of simvastatin and ezetimibe (Vytorin™

), atorvastatin and amlodipine (Caduet™

), and lovastatin and nicotinic acid (Advicor™

);

said angiotensin II receptor antagonist is selected from the group consisting of valsartan, losartan, irbesartan, candesartan celexetil, olmesartan, a combination of losartan and hydrochlorothiazide, and a combination of valsartan and hydrochlorothiazide;

said ACE inhibitor is selected from the group consisting of benazepril, captopril, lisinopril, ramipril, enalapril, a combination of lisinopril and hydrochlorothiazide, and a combination of benazepril and amlodipine;

said antidepressant is selected from the group consisting of amitriptyline, imipramine, desipramine, dapoxetine, venlafaxin, bupropion, paroxetine, citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and zimelidine;

said anticonvulsant is selected from the group consisting of pregabalin, gabapentin, carbamazepine, lamotrigine, and topiramate;

said opioid is selected from morphine, codeine, thebaine, hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, nicomorphine, dipropanoylmorphine, benzylmorphine, ethylmorphine, fentanyl, pethidine, methadone, tramadol and propoxyphene;

said aldose reductase inhibitor is selected from epalrestat and ranirestat;

said pancreatic lipase inhibitor is orlistat;

said serotonin-norepinephrine reuptake inhibitor is sibutramine;

said cannabinoid receptor antagonist is selected from the group consisting of rimonabant and MK-0364;

said anti-obesity combination therapy is selected from the group consisting of a combination of topiramate and phentermine, a combination of bupropion and zonisamide, a combination of bupropion and naltrexone, a combination of phentermine and fluoxetine, a combination of phentermine and sertraline, a combination of phentermine and citalopram, a combination of phentermine and escitalopram, and a combination of phentermine and trazadone;

said erectile dysfunction medication is selected from the group consisting of alprostadil, tadalafil, vardenafil, and sildenafil,

said fish oil is selected from the group consisting of eicosapentaenoic acid “

EPA” and

docosahexaenoic acid (“

DHA”

) and combinations thereof; and

,

said plant sterols and stanols are selected from the group consisting of β

-sitosterol, β

-sitostanol, campesterol, sigmasterol and combinations thereof.

129. A method of treating diabetes, a diabetes related ailment, and/or a disease or condition other than diabetes in a patient in need thereof, said method comprising administering to said patient a composition selected from the group consisting of the pharmaceutical composition of claim 1 and the pharmaceutical composition of claim 33.

4-32. -32. (canceled)

33. A pharmaceutical composition comprising,

oral HDV insulin, and

one or more additional therapeutic agents not associated with oral HDV insulin.

34. The pharmaceutical composition of claim 33, wherein said one or more additional therapeutic agents not associated with oral HDV insulin are selected from the group consisting of an α

-glucosidase inhibitor, a lipase inhibitor, a sulfonyl urea, a meglitinide, a biguanide, a thiazolidinedione, pramlintide, an incretin mimetic, GLP-1 receptor agonist, a DPP-IV inhibitor, asprin, niacin, a fibrate, a bile acid sequestrant, a cholesterol absorption inhibitor, an omega-3 acid ethyl ester, a secretory phospholipase A2 (“

sPLA2”

) inhibitor, an oligonucleotide-based apolipoprotein B (“

apoB”

) inhibitor, a squalene synthase inhibitor, a statin, a fixed dose combination statin therapy, glucose, glucagon, heparin, an angiotensin II receptor antagonist, an ACE inhibitor, an antidepressant, an anticonvulsant, an opioid, C-peptide, an aldose reductase inhibitor, a pancreatic lipase inhibitor, a serotonin-norepinephrine reuptake inhibitor, a cannabinoid (“

CB1”

) receptor antagonist, a leptin receptor agonist, oxyntomodulin or an oxyntomodulin-derived peptide, peptide tyrosine-tyrosine (PYY), an anti-obesity therapy, an anti-obesity combination therapy, an erectile dysfunction medication, an alpha-1-adrenergic receptor blocker, a 5-alpha reductase inhibitor, fish oil, plant sterols and stanols, immunosuppressors, SGLT2 inhibitors, 11β

HSD1 inhibitors, adenosine A1 receptor agonists, anti-inflammatory agents, artificial sweeteners, bile acid receptor agonists, CCK receptor antagonists, CCR2 antagonists, diacylglycerol O-acyltransferase homolog 1 (DGAT-1) inhibitors, dopamine receptor agonists, dual-acting peptide-GLP-1 and glucagons receptor agonists, FGF-21 variants, fructose 1,6 bisphosphatase inhibitors, gastrin-releasing peptide (GRP) receptor agonists, GLP-1 analogs, glucagons receptor antisense, glucokinase activators, glucose-dependent insulinotropic receptor (GDIR/GPR119) agonists, glutamic acid decarboxylases, HM74a agonists, HSP60 peptides, IL-1 antibody (Eli Lilly), insulin-derived peptides, longer acting human GLP-1 analogues, MAbs to CD3, MAbs to glucagon receptors, MAbs to IL-1, MAbs to IL-1β

, permeability inhibitors, plasmid encoding proinsulins, poly(ADP-ribose) polymerase inhibitors, PPAR agonists, PPAR alpha activators, PPAR gamma modulators, PPAR pan agonists, PPARα

/γ

modulators, protein tyrosine phosphatase 1B inhibitor, SGLT1 inhibitors, SIAC (soluble insulin analogue combination, soluble insulin basal analogues, sirtuin (SIRT1) activators, sodium channel blockers, other non-insulin compounds, and combinations thereof.

35. The pharmaceutical composition of claim 34, wherein

said α

-glucosidase inhibitor is selected from the group consisting of acarbose, miglitol, and voglibose;

said lipase inhibitor is orlistat;

said sulfonyl urea is selected from the group consisting of acetohexamide, chlorpropamide, tolbutamide, tolazamide, gliclazide, glyburide, glibenclamide, glipizide, glimepiride, and gliquidone;

said meglitinide is selected from mitiglinide, nateglinide, and repaglinide;

said biguanide is selected from the group consisting of metformin, phenformin, and buformin;

said thiazolidinedione is selected from the group consisting of rosiglitazone, pioglitazone, troglitazone, and tesaglitazar;

said incretin mimetic is selected from the group consisting of exenatide and liraglutide;

said DPP-IV inhibitor is selected from the group consisting of sitagliptin, a combination of sitagliptin and metformin, vildagliptin, alogliptin, a combination of alogliptin and metformin, saxagliptin, and a combination of vildagliptin and metformin;

said fibrate is selected from the group consisting of fenofibrate, bezafibrate, and gemfibrozil;

said bile acid sequestrant is selected from the group consisting of colesevelam and cholestyramine;

wherein said cholesterol absorption inhibitor is selected from the group consisting of ezetimibe, FM-VP4, AEGR-733, implitapide and JTT-130;

said omega-3 acid ethyl ester is selected from the group consisting of Omacor™

, Esapent™

, Seacor™

, and Maxepa™

;

said secretory phospholipase A2 inhibitor is selected from the group consisting of S-5920, LY315920, and A-002;

said oligonucleotide-based apolipoprotein B inhibitor is mipomersen sodium;

said statin is selected from the group consisting of mevastatin, lovastatin, simvastatin, pravastatin, fluvastatin, pitavastatin, atorvastatin, cerivastatin, and rosuvastatin;

said squalene synthase inhibitor is lapaquisatat;

said fixed dose combination stalin therapy is selected from the group consisting of simvastatin and ezetimibe (Vytorin™

), atorvastatin and amlodipine (Caduet™

), and lovastatin and nicotinic acid (Advicor™

);

said angiotensin II receptor antagonist is selected from the group consisting of valsartan, losartan, irbesartan, candesartan celexetil, olmesartan, a combination of losartan and hydrochlorothiazide, and a combination of valsartan and hydrochlorothiazide;

said ACE inhibitor is selected from the group consisting of benazepril, captopril, lisinopril, ramipril, enalapril, a combination of lisinopril and hydrochlorothiazide, and a combination of benazepril and amlodipine;

said antidepressant is selected from the group consisting of amitriptyline, imipramine, desipramine, duloxetine, venlafaxin, bupropion, paroxetine, citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and zimelidine;

said anticonvulsant is selected from the group consisting of pregabalin, gabapentin, carbamazepine, lamotrigine, and topiramate;

said opioid is selected from morphine, codeine, thebaine, hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, nicomorphine, dipropanoylmorphine, benzylmorphine, ethylmorphine, fentanyl, pethidine, methadone, tramadol and propoxyphene;

said aldose reductase inhibitor is selected from epairestat and ranirestat;

said pancreatic lipase inhibitor is orlistat;

said serotonin-norepinephrine reuptake inhibitor is sibutramine;

said cannabinoid receptor antagonist is selected from the group consisting of rimonabant and MK-0364;

said anti-obesity combination therapy is selected from the group consisting of a combination of topiramate and phentermine, a combination of bupropion and zonisamide, a combination of bupropion and naltrexone, a combination of phentermine and fluoxetine, a combination of phentermine and sertraline, a combination of phentermine and citalopram, a combination of phentermine and escitalopram, and a combination of phentermine and trazadone;

said erectile dysfunction medication is selected from the group consisting of alprostadil, tadalafil, vardenafil, and sildenafil;

said fish oil is selected from the group consisting of eicosapentaenoic acid (“

EPA”

) and docosahexaenoic acid (“

DHA”

) and combinations thereof; and

said plant sterols and stanols are selected from the group consisting of β

-sitosterol, β

-sitostanol, campesterol, sigmasterol and combinations thereof.

36-64. -64. (canceled)

65. A method of preparing a pharmaceutical composition comprising HDV insulin and one or more additional therapeutic agents not associated with HDV insulin, said method comprising the steps of:

a. mixing lipid components and at least one targeting agent in aqueous media to form a first mixture;

b. adding at least one insulin to said first mixture to form a second mixture; and

c. formulating said second mixture with said one or more additional therapeutic agents.

67. The method of claim 65, wherein said one or more therapeutic agents are selected from the group consisting of an α

-glucosidase inhibitor, a lipase inhibitor, a sulfonyl urea, a meglitinide, a biguanide, a thiazolidinedione, pramlintide, an incretin mimetic, GLP-1 receptor agonist, a DPP-IV inhibitor, asprin, niacin, a fibrate, a bile acid sequestrant, a cholesterol absorption inhibitor, an omega-3 acid ethyl ester, a secretory phospholipase A2 (“

sPLA2”

) inhibitor, an oligonucleotide-based apolipoprotein B (“

apoB”

) inhibitor, a squalene synthase inhibitor, a statin, a fixed dose combination statin therapy, glucose, glucagon, heparin, an angiotensin II receptor antagonist, an ACE inhibitor, an antidepressant, an anticonvulsant, an opioid, C-peptide, an aldose reductase inhibitor, a pancreatic lipase inhibitor, a serotonin-norepinephrine reuptake inhibitor, a cannabinoid (“

CB1”

) receptor antagonist, a leptin receptor agonist, oxyntomodulin or an oxyntomodulin-derived peptide, peptide tyrosine-tyrosine (PYY), an anti-obesity therapy, an anti-obesity combination therapy, an erectile dysfunction medication, an alpha-1-adrenergic receptor blocker, a 5-alpha reductase inhibitor, fish oil, plant sterols and stanols, immunosuppressors, SGLT2 inhibitors, 11β

HSD1 inhibitors, adenosine A1 receptor agonists, anti-inflammatory agents, artificial sweeteners, bile acid receptor agonists, CCK receptor antagonists, CCR2 antagonists, diacylglycerol O-acyltransferase homolog 1 (DGAT-1) inhibitors, dopamine receptor agonists, dual-acting peptide-GLP-1 and glucagons receptor agonists, FGF-21 variants, fructose 1,6 bisphosphatase inhibitors, gastrin-releasing peptide (GRP) receptor agonists, GLP-1 analogs, glucagons receptor-antisense, glucokinase activators, glucose-dependent insulinotropic receptor (GDIR/GPR119) agonists, glutamic acid decarboxylases, HM74a agonists, HSP60 peptides, IL-1 antibody (Eli Lilly), insulin-derived peptides, longer acting human GLP-1 analogues, MAbs to CD3, MAbs to glucagon receptors, MAbs to IL-1, MAbs to IL-1β

, permeability inhibitors, plasmid encoding proinsulins, poly(ADP-ribose) polymerase inhibitors, PPAR agonists, PPAR alpha activators, PPAR gamma modulators, PPAR pan agonists, PPARα

/γ

modulators, protein tyrosine phosphatase 1B inhibitor, SGLT1 inhibitors, SIAC (soluble insulin analogue combination, soluble insulin basal analogues, sirtuin (SIRT1) activators, sodium channel blockers, other non-insulin compounds, and combinations thereof.

68. The method of claim 67, wherein said

α

-glucosidase inhibitor is selected from the group consisting of acarbose, and voglibose;

said lipase inhibitor is orlistat;

said sulfonyl urea is selected from the group consisting of acetohexamide, chlorpropamide, tolbutamide, tolazamide, gliclazide, glyburide, glibenclamide, glipizide, glimepiride, and gliquidone;

said meglitinide is selected from mitiglinide, nateglinide, and repaglinide;

said biguanide is selected from the group consisting of metformin, phenformin, and buformin;

said thiazolidinedione is selected from the group consisting of rosiglitazone, pioglitazone, troglitazone, and tesaglitazar;

said incretin mimetic is selected from the group consisting of exenatide and liraglutide;

said DPP-IV inhibitor is selected from the group consisting of sitagliptin, a combination of sitagliptin and metformin, vildagliptin, alogliptin, a combination of alogliptin and metformin, saxagliptin, and a combination of vildagliptin and metformin;

said fibrate is selected from the group consisting of fenofibrate, bezafibrate, and gemfibrozil;

said bile acid sequestrant is selected from the group consisting of colesevelam and cholestyramine;

wherein said cholesterol absorption inhibitor is selected from the group consisting of ezetimibe, FM-VP4, AEGR-733, implitapide and JTT-130;

said omega-3 acid ethyl ester is selected from the group consisting of Omacor™

, Esapent™

, Seacor™

, and Maxepa™

;

said secretory phospholipase A2 inhibitor is selected from the group consisting of S-5920, LY315920, and A-002;

said oligonucleotide-based apolipoprotein B inhibitor is mipomersen sodium;

said statin is selected from the group consisting of mevastatin, lovastatin, simvastatin, pravastatin, fluvastatin, pitavastatin, atorvastatin, cerivastatin, and rosuvastatin;

said squalene synthase inhibitor is lapaquisatat;

said fixed dose combination statin therapy is selected from the group consisting of simvastatin and ezetimibe (Vytorin™

), atorvastatin and amlodipine (Caduet™

), and lovastatin and nicotinic acid (Advicor™

);

said angiotensin II receptor antagonist is selected from the group consisting of valsartan, losartan, irbesartan, candesartan celexetil, olmesartan, a combination of losartan and hydrochlorothiazide, and a combination of valsartan and hydrochlorothiazide;

said ACE inhibitor is selected from the group consisting of benazepril, captopril, lisinopril, ramipril, enalapril, a combination of lisinopril and hydrochlorothiazide, and a combination of benazepril and amlodipine;

said antidepressant is selected from the group consisting of amitriptyline, imipramine, desipramine, duloxetine, venlafaxin, bupropion, paroxetine, citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and zimelidine;

said anticonvulsant is selected from the group consisting of pregabalin, gabapentin, carbamazepine, lamotrigine, and topiramate;

said opioid is selected from morphine, codeine, thebaine, hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, nicomorphine, dipropanoylmorphine, benzylmorphine, ethylmorphine, fentanyl, pethidine, methadone, tramadol and propoxyphene;

said aldose reductase inhibitor is selected from epalrestat and ranirestat;

said pancreatic lipase inhibitor is orlistat;

said serotonin-norepinephrine reuptake inhibitor is sibutramine;

said cannabinoid receptor antagonist is selected from the group consisting of rimonabant and MK-0364;

said anti-obesity combination therapy is selected from the group consisting of a combination of topiramate and phentermine, a combination of bupropion and zonisamide, a combination of bupropion and naltrexone, a combination of phentermine and fluoxetine, a combination of phentermine and sertraline, a combination of phentermine and citalopram, a combination of phentermine and escitalopram, and a combination of phentermine and trazadone;

said erectile dysfunction medication is selected from the group consisting of alprostadil, tadalafll, vardenafil, and sildenafil;

said fish oil is selected from the group consisting of eicosapentaenoic acid (“

EPA”

) and docosahexaenoic acid (“

DHA”

) and combinations thereof; and

said plant sterols and stanols are selected from the group consisting of β

-sitosterol, β

-sitostanol, campesterol, sigmasterol and combinations thereof.

66. A method of preparing a pharmaceutical composition comprising oral HDV insulin and one or more additional therapeutic agents not associated with oral HDV insulin, said method comprising the steps of:

a. forming oral HDV insulin by;

i. mixing lipid components and, optionally, at least one targeting agent in aqueous media to form a first mixture;

ii. adding at least one insulin to said first mixture to form a second mixture;

iii. adding said second mixture to gelatin to form a gelatin-associated mixture;

iv. drying said gelatin-associated mixture to form a dry mixture of oral HDV insulin; and

b. formulating said dry mixture of oral HDV insulin with said one or more additional therapeutic agents not associated with oral HDV insulin.

98. The method of claim 66, wherein said one or more therapeutic agents are selected from the group consisting of an α

-glucosidase inhibitor, a lipase inhibitor, a sulfonyl urea, a meglitinide, a biguanide, a thiazolidinedione, pramlintide, an incretin mimetic, GLP-1 receptor agonist, a DPP-IV inhibitor, asprin, niacin, a fibrate, a bile acid sequestrant, a cholesterol absorption inhibitor, an omega-3 acid ethyl ester, a secretory phospholipase A2 (“

sPLA2”

) inhibitor, an oligonucleotide-based apolipoprotein B (“

apoB”

) inhibitor, a squalene synthase inhibitor, a statin, a fixed dose combination statin therapy, glucose, glucagon, heparin, an angiotensin II receptor antagonist, an ACE inhibitor, an antidepressant, an anticonvulsant, an opioid, C-peptide, an aldose reductase inhibitor, a pancreatic lipase inhibitor, a serotonin-norepinephrine reuptake inhibitor, a cannabinoid (“

CB1”

) receptor antagonist, a leptin receptor agonist, oxyntomodulin or an oxyntomodulin-derived peptide, peptide tyrosine-tyrosine (PYY), an anti-obesity therapy, an anti-obesity combination therapy, an erectile dysfunction medication, an alpha-1-adrenergic receptor blocker, a 5-alpha reductase inhibitor, fish oil, plant sterols and stanols, immunosuppressors, SGLT2 inhibitors, 11β

SD1 inhibitors, adenosine A1 receptor agonists, anti-inflammatory agents, artificial sweeteners, bile acid receptor agonists, CCK receptor antagonists, CCR2 antagonists, diacylglycerol O-acyltransferase homolog 1 (DGAT-1) inhibitors, dopamine receptor agonists, dual-acting peptide-GLP-1 and glucagons receptor agonists, FGF-21 variants, fructose 1,6 bisphosphatase inhibitors, gastrin-releasing peptide (GRP) receptor agonists, GLP-1 analogs, glucagons receptor-antisense, glucokinase activators, glucose-dependent insulinotropic receptor (GDIR/GPR119) agonists, glutamic acid decarboxylases, HM74a agonists, HSP60 peptides, IL-1 antibody (Eli Lilly), insulin-derived peptides, longer acting human GLP-1 analogues, MAbs to CD3, MAbs to glucagon receptors, MAbs to IL-1, MAbs to IL-1β

, permeability inhibitors, plasmid encoding proinsulins, poly(ADP-ribose) polymerase inhibitors, PPAR agonists, PPAR alpha activators, PPAR gamma modulators, PPAR pan agonists, PPARα

/γ

modulators, protein tyrosine phosphatase 1B inhibitor, SGLT1 inhibitors, SIAC (soluble insulin analogue combination, soluble insulin basal analogues, sirtuin (SIRT1) activators, sodium channel blockers, other non-insulin compounds, and combinations thereof.

99. The method of claim 98, wherein

said α

-glucosidase inhibitor is selected from the group consisting of acarbose, miglitol, and voglibose;

said lipase inhibitor is orlistat;

said sulfonyl urea is selected from the group consisting of acetohexamide, chlorpropamide, tolbutamide, tolazamide, gliclazide, glyburide, glibenclamide, glipizide, glimepiride, and gliquidone;

said meglitinide is selected from mitiglinide, nateglinide, and repaglinide;

said biguanide is selected from the group consisting of metformin, phenformin, and buformin;

said thiazolidinedione is selected from the group consisting of rosiglitazone, pioglitazone, troglitazone, and tesaglitazar;

said incretin mimetic is selected from the group consisting of exenatide and liraglutide;

said DPP-IV inhibitor is selected from the group consisting of sitagliptin, a combination of sitagliptin and metformin, vildagliptin, alogliptin, a combination of alogliptin and metformin, saxagliptin, and a combination of vildagliptin and metformin;

said fibrate is selected from the group consisting of fenofibrate, bezafibrate, and gemfibrozil;

said bile acid sequestrant is selected from the group consisting of colesevelam and cholestyramine;

wherein said cholesterol absorption inhibitor is selected from the group consisting of ezetimibe, FM-VP4, AEGR-733, implitapide and JTT-130

said omega-3 acid ethyl ester is selected from the group consisting of Omacor™

, Esapent™

, Seacor™ and

Maxepa™

;

said secretory phospholipase A2 inhibitor is selected from the group consisting of S-5920, LY315920, and A-002;

said oligonucleotide-based apolipoprotein B inhibitor is mipomersen sodium;

said statin is selected from the group consisting of mevastatin, lovastatin, simvastatin, pravastatin, fluvastatin, pitavastatin, atorvastatin, cerivastatin, and rosuvastatin;

said squalene synthase inhibitor is lapaquisatat;

said fixed dose combination statin therapy is selected from the group consisting of simvastatin and ezetimibe (Vytorin™

), atorvastatin and amlodipine (Caduet™

), and lovastatin and nicotinic acid (Advicor™

);

said angiotensin II receptor antagonist is selected from the group consisting of valsartan, losartan, irbesartan, candesartan celexetil, olmesartan, a combination of losartan and hydrochlorothiazide, and a combination of valsartan and hydrochlorothiazide;

said ACE inhibitor is selected from the group consisting of benazepril, captopril lisinopril, ramipril, enalapril, a combination of lisinopril and hydrochlorothiazide, and a combination of benazepril and amlodipine;

said antidepressant is selected from the group consisting of amitriptyline, imipramine, desipramine, duloxetine, venlafaxin, bupropion, paroxetine, citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and zimelidine;

said anticonvulsant is selected from the group consisting of pregabalin, gabapentin, carbamazepine, lamotrigine, and topiramate;

said opioid is selected from morphine, codeine, thebaine, hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, nicomorphine, dipropanoylmorphine, benzylmorphine, ethylmorphine, fentanyl, pethidine, methadone, tramadol and propoxyphene;

said aldose reductase inhibitor is selected from epalrestat and ranirestat;

said pancreatic lipase inhibitor is orlistat;

said serotonin-norepinephrine reuptake inhibitor is sibutramine;

said cannabinoid receptor antagonist is selected from the group consisting of rimonabant and MK-0364;

said anti-obesity combination therapy is selected from the group consisting of a combination of topiramate and phentermine, a combination of bupropion and zonisamide, a combination of bupropion and naltrexone, a combination of phentermine and fluoxetine, a combination of phentermine and sertraline, a combination of phentermine and citalopram, a combination of phentermine and escitalopram, and a combination of phentermine and trazadone;

said erectile dysfunction medication is selected from the group consisting of alprostadil, tadalafil, vardenafil, and sildenafil;

said fish oil is selected from the group consisting of eicosapentaenoic acid (“

EPA”

) and docosahexaenoic acid (“

DHA”

) and combinations thereof; and

said plant sterols and stanols are selected from the group consisting of β

-sitosterol, β

-sitostanol, campesterol, sigmasterol and combinations thereof.

69-97. -97. (canceled)

100-128. -128. (canceled)

130. (canceled)

131. A method of treating a diabetes related ailment and/or a disease or conditions other than diabetes or a diabetes related ailment in a patient in need thereof, said method comprising

administering to said patient a pharmaceutical formulation of HDV insulin or pharmaceutical formulation of oral HDV insulin, and

optionally co-administering to said patient one or more additional therapeutic agents not associated with said HDV insulin or said oral HDV insulin.

132. The method of claim 131, wherein said diabetes related ailment and disease or condition other than diabetes is selected from the group consisting of, obesity, fatty liver, cardiovascular disease, diabetic coma, diabetic nephrophathy, diabetic neuropathy, erectile dysfunction, metabolic syndrome, diabetic retinopathy, peripheral insulin level elevation, pre-diabetes, cerebral vasospasm, coronary vasospasm, bronchial asthma, preterm labor, glaucoma, vascular smooth muscle cell proliferation, myocardial hypertrophy, malignoma, ischemia/reperfusion-induced injury, endothelial dysfunction, Crohn'"'"'s Disease and colitis, neurite outgrowth, Raynaud'"'"'s Disease, angina, Alzheimer'"'"'s disease, or benign prostatic hyperplasia, peripheral vascular disease, gout, dementia, and loss of mental acuity.

135. The method according to claim 131 wherein said one or more additional therapeutic agent is selected from the group consisting of an α

-glucosidase inhibitor, a lipase inhibitor, a sulfonyl urea, a meglitinide, a biguanide, a thiazolidinedione, pramlintide, an incretin mimetic, GLP-1 receptor agonist, a DPP-IV inhibitor, aspirin, niacin, a fibrate, a bile acid sequestrant, a cholesterol absorption inhibitor, an omega-3 acid ethyl ester, a secretory phospholipase A2 (“

sPLA2”

) inhibitor, an oligonucleotide-based apolipoprotein B (“

apoB”

) inhibitor, a squalene synthase inhibitor, a statin, a fixed dose combination statin therapy, glucose, glucagon, heparin, an angiotensin II receptor antagonist, an ACE inhibitor, an antidepressant, an anticonvulsant, an opioid, C-peptide, an aldose reductase inhibitor, a pancreatic lipase inhibitor, a serotonin-norepinephrine reuptake inhibitor, a cannabinoid (“

CB1”

) receptor antagonist, a leptin receptor agonist, oxyntomodulin or an oxyntomodulin-derived peptide, peptide tyrosine-tyrosine (PYY), an anti-obesity therapy, an anti-obesity combination therapy, an erectile dysfunction medication, an alpha-1-adrenergic receptor blocker, a 5-alpha reductase inhibitor, fish oil, plant sterols and stanols, immunosuppressors, SGLT2 inhibitors, 11β

HSD1 inhibitors, adenosine A1 receptor agonists, anti-inflammatory agents, artificial sweeteners, bile acid receptor agonists, CCK receptor antagonists, CCR2 antagonists, diacylglycerol O-acyltransferase homolog 1 (DGAT-1) inhibitors, dopamine receptor agonists, dual-acting peptide-GLP-1 and glucagons receptor agonists, FGF-21 variants, fructose 1,6 bisphosphatase inhibitors, gastrin-releasing peptide (GRP) receptor agonists, GLP-1 analogs, glucagons receptor-antisense, glucokinase activators, glucose-dependent insulinotropic receptor (GDIR/GPR119) agonists, glutamic acid decarboxylases, HM74a agonists, HSP60 peptides, IL-1 antibody (Eli Lilly), insulin-derived peptides, longer acting human GLP-1 analogues, MAbs to CD3, MAbs to glucagon receptors, MAbs to IL-1, MAbs to IL-1β

, permeability inhibitors, plasmid encoding proinsulins, poly(ADP-ribose) polymerase inhibitors, PPAR agonists, PPAR alpha activators, PPAR gamma modulators, PPAR pan agonists, PPARα

/γ

modulators, protein tyrosine phosphatase 1B inhibitor, SGLT1 inhibitors, SIAC (soluble insulin analogue combination, soluble insulin basal analogues, sirtuin (SIRT1) activators, sodium channel blockers, other non-insulin compounds, and combinations thereof.

133-134. -134. (canceled)

136. A kit comprising

a. a pharmaceutical composition comprising an insulin selected from the group consisting of HDV insulin and oral HDV insulin, and one or more additional therapeutic agents not associated with said insulin;

and

b. instructional material for administration of said composition to a human.

137. (canceled)

138. A kit comprising

a. a pharmaceutical formulation of an insulin selected from the group consisting of HDV insulin and oral HDV insulin, and one or more additional therapeutic agents for co-administration;

and

b. instructional material for co-administration of said pharmaceutical formulation of insulin and said therapeutic agents to a human.

139. (canceled)