US20160287674A1 - Treatment Type 2 Diabetes Mellitus Patients - Google Patents

Treatment Type 2 Diabetes Mellitus Patients Download PDF

Info

Publication number
US20160287674A1
US20160287674A1 US15/068,286 US201615068286A US2016287674A1 US 20160287674 A1 US20160287674 A1 US 20160287674A1 US 201615068286 A US201615068286 A US 201615068286A US 2016287674 A1 US2016287674 A1 US 2016287674A1
Authority
US
United States
Prior art keywords
insulin
plasma glucose
patient
pharmaceutically acceptable
acceptable salt
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US15/068,286
Other languages
English (en)
Inventor
Christine Roy
Elisabeth SOUHAMI
Nacima Demil
Jenny Ye
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis Deutschland GmbH
Original Assignee
Sanofi Aventis Deutschland GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi Aventis Deutschland GmbH filed Critical Sanofi Aventis Deutschland GmbH
Assigned to SANOFI-AVENTIS DEUTSCHLAND GMBH reassignment SANOFI-AVENTIS DEUTSCHLAND GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ROY, CHRISTINE, SOUHAMI, ELISABETH, DEMIL, Nacima, YE, Jenny
Publication of US20160287674A1 publication Critical patent/US20160287674A1/en
Priority to US15/646,760 priority Critical patent/US10434147B2/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/26—Glucagons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • Subject of the present invention is a pharmaceutical combination for use in glycemic control, for use in the reduction of the HbA1c value, the fasting plasma glucose or/and the 2 hour postprandial plasma glucose, for use in the prevention of weight gain or/and for inducing weight loss, for use in the reduction of the risk of hypoglycemia, in a type 2 diabetes mellitus patient, said combination comprising
  • type 2 diabetes mellitus In contrast to type 1 diabetes, there is not generally a lack of insulin in type 2 diabetes mellitus but in many cases, particularly in progressive cases, the treatment with insulin is regarded as the most suitable therapy, if required in combination with orally administered anti-diabetic drugs.
  • a particular risk exists for overweight patients suffering from type 2 diabetes mellitus e.g. patients with a body mass index (BMI) ⁇ 30 kg/m 2 .
  • BMI body mass index
  • the risks of diabetes overlap with the risks of overweight, leading e.g. to an increase of cardiovascular diseases compared to type 2 diabetes mellitus patients being of a normal weight.
  • the compound desPro 36 Exendin-4(1-39)-Lys 6 -NH 2 (AVE0010, lixisenatide) is a derivative of Exendin-4.
  • AVE0010 is disclosed as SEQ ID NO:93 in WO 01/04156:
  • SEQ ID NO: 1 lixisenatide (44 amino acids) H-G-E-G-T-F-T-S-D-L-S-K-Q-M-E-E-E-A-V-R-L-F-I-E- W-L-K-N-G-G-P-S-S-G-A-P-P-S-K-K-K-K-K-K-NH 2
  • SEQ ID NO: 2 exendin-4 (39 amino acids) H-G-E-G-T-F-T-S-D-L-S-K-Q-M-E-E-E-A-V-R-L-F-I-E- W-L-K-N-G-G-P-S-S-G-A-P-P-S-NH 2
  • Exendins are a group of peptides which can lower blood glucose concentration.
  • the Exendin analogue lixisenatide is characterised by C-terminal truncation of the native Exendin-4 sequence.
  • Lixisenatide comprises six C-terminal lysine residues not present in Exendin-4.
  • Lixisenatide is also termed des-38-proline-exendin-4(He/oderma suspectum)-(1-39)-peptidylpenta-L-lysyl-L-lysinamide (CAS number 320367-13-3).
  • lixisenatide includes pharmaceutically acceptable salts thereof. The person skilled in the art knows suitable pharmaceutically acceptable salts of lixisenatide.
  • Insulin glargine is an analogue of human insulin.
  • Insulin glargine is 31 B -32 B -Di-Arg human insulin with further substitution of asparagine in position A21 by glycine.
  • Insulin glargine is also termed Gly(A21)-Arg(B31)-Arg(B32) human insulin.
  • the CAS number of insulin glargine is 160337-95-1.
  • “insulin glargine” includes pharmaceutically acceptable salts thereof. The person skilled in the art knows suitable pharmaceutically acceptable salts of insulin glargine.
  • Metformin is the international nonproprietary name of 1,1-dimethylbiguanide (CAS number 657-24-9). Metformin is a biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus (type 2 diabetes mellitus) not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Metformin is usually administered orally. However, control of type 2 diabetes mellitus in obese patients by metformin may be insufficient. Thus, in these patients, additional measures for controlling type 2 diabetes mellitus may be required. “Metformin”, as used herein, included pharmaceutically acceptable salts thereof. The person skilled in the art knows suitable pharmaceutically acceptable salts of metformin.
  • the effect of the combination of lixisenatide, insulin glargine and optionally metformin has been tested in obese type 2 diabetes mellitus patients poorly controlled with a basal insulin alone or a basal insulin in combination with one to three oral anti-diabetic drugs selected from metformin, sulfonylureas, dipeptidyl-peptidase-4 (DPP-4) inhibitors and glinides.
  • the diabetes patients still had a fasting plasma glucose concentration of about 9.2 to 9.5 mmol/L and a HbA1c value of about 8.5%.
  • the 2 hour postprandial plasma glucose was about 13.8 to 14.5 mmol/L (249 to 262 mg/dL). These values still exceed normoglycemic values.
  • insulin glargine combined with lixisenatide and optionally metformin may become a preferred option, attaining meaningful glycemic targets with less hypoglycemia and with weight loss compared with prandial insulin (such as insulin glulisine), as basal insulin plus oral anti-diabetic compounds or basal insulin plus prandial insulin (bolus administration) in difficult to control, obese, insulin-treated type 2 diabetes mellitus patients.
  • prandial insulin such as insulin glulisine
  • a first aspect of the present invention is a pharmaceutical combination for use in glycemic control in a type 2 diabetes mellitus patient, said combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the combination as described herein can be used for improving glycemic control.
  • “improvement of glycemic control” or “glycemic control” in particular refers to improvement of the 2 hour postprandial plasma glucose concentration, improvement of fasting plasma glucose concentration, or/and improvement of the HbA 1c value.
  • “improvement of glycemic control” or “glycemic control” includes the improvement of the 2 hour postprandial plasma glucose concentration.
  • “improvement of glycemic control” or “glycemic control” includes the reduction of the 2 hour postprandial plasma glucose concentration. Reduction means in particular that the 2 hour postprandial plasma glucose concentration reaches normoglycemic values or at least approaches these values.
  • “improvement of glycemic control” or “glycemic control” includes the improvement of the fasting plasma glucose concentration.
  • improvement of fasting plasma glucose concentration includes the reduction of the fasting plasma glucose concentration.
  • Reduction means in particular that the fasting plasma glucose concentration reaches normoglycemic values or at least approaches these values.
  • “improvement of glycemic control” or “glycemic control” includes the improvement of the HbA 1c value.
  • improvement of the HbA 1c value includes the reduction of the HbA 1c value.
  • Reduction of the HbA 1c value in particular means that the HbA 1c value is reduced below 6.5% or 7%.
  • Yet another aspect of the present invention is a pharmaceutical combination for use in the improvement of the HbA1c value, the fasting plasma glucose or/and the 2 hour postprandial plasma glucose in a type 2 diabetes mellitus patient, said combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • normoglycemic values are blood glucose concentrations of in particular 60-140 mg/d 1 (corresponding to 3.3 to 7.8 mmol/L). This range refers in particular to blood glucose concentrations under fasting conditions and postprandial conditions.
  • Criteria for a type 2 diabetes mellitus diagnosis include:
  • Type 2 Diabetes should not be based on a single plasma glucose concentration. Diagnosis may require continued observation with fasting or/and postprandial blood glucose levels or/and an oral glucose tolerance test.
  • fasting plasma glucose (FPG) and post challenge (postload) glucose can be classified as follows:
  • OGTT Oral Glucose Tolerance Test
  • Impaired glucose tolerance (IGT) and impaired fasting glucose concentration (IFG) are intermediate stages in the natural history of disordered carbohydrate metabolism between normal glucose homeostasis and diabetes.
  • normoglycemic values of fasting plasma glucose are blood glucose concentrations of in particular ⁇ 5.6 mmol/L.
  • normoglycemic values of postprandial plasma glucose are blood glucose concentrations of in particular ⁇ 7.8 mmol/L.
  • not adequately controlled by a particular anti-diabetic treatment means that this treatment is not sufficient to remove the symptoms of type 2 diabetes mellitus.
  • “not adequately controlled” by this treatment means that the patient does not reach normoglycemic values in terms of, for example, 2 hour postprandial plasma glucose concentration, HbA1c value or/and fasting plasma glucose concentration.
  • the type 2 diabetes mellitus patient to be treated according to the present invention may be a subject suffering from type 2 diabetes mellitus, wherein type 2 diabetes mellitus is not adequately controlled by treatment with a basal insulin monotherapy.
  • the type 2 diabetes mellitus patient to be treated according to the present invention may be a subject suffering from type 2 diabetes mellitus, wherein type 2 diabetes mellitus is not adequately controlled by treatment with a combination of a basal insulin and metformin alone, for instance with (a) a dose of at least 1.0 g/day metformin or at least 1.5 g/day metformin for at least 3 months, or/and (b) a dose of at the maximum 2.0 g/day metformin for at least 3 months or at the maximum 3.5 g/day metformin for at least 3 months.
  • the type 2 diabetes mellitus patient to be treated according to the present invention may be a subject suffering from type 2 diabetes mellitus, wherein the type 2 diabetes mellitus to be treated is not adequately controlled with compound (b) and optionally compound (c) alone.
  • Basal insulin includes insulin glargine, insulin detemir and isophane insulin (NPH insulin).
  • the basal insulin is in particular selected from insulin glargine, insulin detemir and isophane insulin (NPH insulin).
  • “to be treated according to the present invention”, “treatment according to the present invention”, or “therapy according to the present invention” relates to the treatment of a type 2 diabetes mellitus patient by the pharmaceutical combination comprising
  • a further aspect of the present invention is a pharmaceutical combination for use in the prevention of weight gain or/and for inducing weight loss, in a type 2 diabetes mellitus patient, said combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the examples of the present invention demonstrate that the claimed combination can reduce body weight in type 2 diabetes patients, as defined herein, wherein the comparative treatment (insulin glulisine once daily or three times daily) induces a significant weight gain.
  • Yet another aspect of the present invention is a pharmaceutical combination for use in the reduction of the risk of hypoglycemia, in a type 2 diabetes mellitus patient, said combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the examples of the present invention demonstrate that documented hypoglycemia was numerically and significantly lower with the claimed combination in view of the comparative treatment with insulin glulisine once daily or three times daily.
  • hypoglycemia is the critical limiting factor in the glycemic management of diabetes in both the short and long term. Despite steady improvements in the glycemic management of diabetes, population-based data indicate that hypoglycemia continues to be a major problem for people with both type 1 and type 2 diabetes (American diabetes association, workgroup on hypoglycemia: Defining and Reporting Hypoglycemia in Diabetes. Diabetes Care 28(5), 2005, 1245-1249).
  • the combination of the present invention can prevent hypoglycemia when administered to a type 2 diabetes mellitus patient, as described herein.
  • Prevention of hypoglycemia includes reduction of the number of hypoglycemic events and/or the severity of hypoglycemia events.
  • the combination as described herein is suitable for use in the prevention of hypoglycemia.
  • hypoglycemia is a condition wherein a type 2 diabetes mellitus patient experiences a plasma glucose concentration of below 70 mg/dL (or below 3.9 mmol/L), below 60 mg/dL (or below 3.3 mmol/L), below 54 mg/dL (or below 3.0 mmol/L), below 50 mg/dL, below 40 mg/dL, or below 36 mg/dL.
  • symptomatic hypoglycemia or “symptomatic hypoglycemic event” is a condition associated with a clinical symptom that results from the hypoglycemia, wherein the plasma glucose concentration can be below 70 mg/dL (or below 3.9 mmol/L), below 60 mg/dL (or below 3.3 mmol/L), below 54 mg/dL (or below 3.0 mmol/L), below 50 mg/dL, or below 40 mg/dL.
  • a clinical symptom can be, for example, sweating, palpitations, hunger, restlessness, anxiety, fatigue, irritability, headache, loss of concentration, somnolence, psychiatric disorders, visual disorders, transient sensory defects, transient motor defects, confusion, convulsions, and coma.
  • one or more clinical symptoms of symptomatic hypoglycemia can be selected.
  • Symptomatic hypoglycemia may be associated with prompt recovery after oral carbohydrate administration.
  • a symptomatic hypoglycemia event preferably has a plasma glucose concentration of below 60 mg/dL (or below 3.3 mmol/L).
  • “severe symptomatic hypoglycemia” or “severe symptomatic hypoglycemic event” is a condition with a clinical symptom, as indicated herein, that results from hypoglycemia, wherein the plasma glucose concentration can be below 70 mg/dL (or below 3.9 mmol/L), below 54 mg/dL (or below 3.0 mmol/L) or below 36 mg/dL (or below 2.0 mmol/L).
  • Severe symptomatic hypoglycemia can be associated with acute neurological impairment resulting from the hypoglycemic event.
  • the patient may require the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
  • a severe symptomatic hypoglycemia event preferably has a plasma glucose concentration of below 36 mg/dL (or below 2.0 mmol/L).
  • severe symptomatic hypoglycemia may include all episodes in which neurological impairment is severe enough to prevent self-treatment and which were thus thought to place patients at risk for injury to themselves or others.
  • the acute neurological impairment may be at least one selected from somnolence, psychiatric disorders, visual disorders, transient sensory defects, transient motor defects, confusion, convulsions, and coma.
  • “Requires assistance” means that the patient could not help himself or herself. Assisting a patient out of kindness, when assistance is not required, should not be considered a “requires assistance” incident.
  • Severe symptomatic hypoglycemia may be associated with prompt recovery after oral carbohydrate, intravenous glucose, or/and glucagon administration.
  • “documented symptomatic hypoglycemia” or “documented symptomatic hypoglycemic event” is an event during which typical symptoms of hypoglycemia accompanied by a measured plasma glucose concentration of 5. 70 mg/dL (5. 3.9 mmol/L), or less than or equal to 54 mg/dL (5 3.0 mmol/L).
  • Clinical symptoms that are considered to result from a hypoglycemic episode are, e.g., increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, coma.
  • asymptomatic hypoglycemia or “asymptomatic hypoglycemic event” is an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration less than or equal to 70 mg/dL (3.9 mmol/L), or less than or equal to 54 mg/dL (3.0 mmol/L).
  • probable symptomatic hypoglycemia or “probable symptomatic hypoglycemic event” is an event during which symptoms of hypoglycemia are not accompanied by a plasma glucose determination, but was presumably caused by a plasma glucose concentration less than or equal to 70 mg/dL (or less than or equal to 3.9 mmol/L), or less than or equal to 54 mg/dL (or less than or equal to 3.0 mmol/L); symptoms treated with oral carbohydrate without a test of plasma glucose.
  • “relative hypoglycemia” or “relative hypoglycemic event” is an event during which the person with diabetes reports any of the typical symptoms of hypoglycemia, and interprets the symptoms as indicative of hypoglycemia, but with a measured plasma glucose concentration greater than 70 mg/dL (or greater than 3.9 mmol/L).
  • the hypoglycemia can be a symptomatic hypoglycemia, a severe symptomatic hypoglycemia, a documented symptomatic hypoglycemia, a probable symptomatic hypoglycemia, a relative symptomatic hypoglycemia, or an asymptomatic hypoglycemia.
  • a symptomatic hypoglycemia more preferably a severe symptomatic hypoglycemia. “Reducing the risk of hypoglycemia”, as used herein, can include reducing the incidence of hypoglycemia.
  • the incidence of hypoglycemia per patient year can be computed per patient as: 365.25 ⁇ (number of episodes of hypoglycemia)/(number of days exposed) and summarized by type of event and treatment group. “Reducing the risk of hypoglycemia”, as used herein, can further include prevention of hypoglycemia in a patient, when the formulation described herein is administered to a type 2 diabetes mellitus patient, as described herein. “Reducing the risk of hypoglycemia”, as used herein, can further include reduction of the number of hypoglycemic events, and/or the severity of hypoglycemia events.
  • the type 2 diabetes mellitus patient suffering from type 2 diabetes mellitus to be treated according to the present invention may be obese.
  • a patient can be considered as obese if the body mass index is at least 30 kg/m 2 .
  • an obese type 2 diabetes mellitus patient may have a body mass index of at least 30 kg/m 2 .
  • the obese type 2 diabetes mellitus patient may have a body weight of at least 87 kg, at least 88 kg, at least 89 kg or at least 90 kg.
  • the type 2 diabetes mellitus patient may be obese prior to the onset of therapy with the combination according to the present invention.
  • the patient to be treated may have an age of less than 50 years.
  • the patient may also have an age of at least 50 years, or an age in the range of 50 to 64 years.
  • the patient may also have an age of at least 65 years, or an age in the range of 65 to 74 years.
  • the patient may also have an age of at least 75 years. It is preferred that the patient has an age of at least 65 years.
  • the type 2 diabetes mellitus to be treated according to the present invention may suffer from a type 2 diabetes mellitus not adequately controlled with a basal insulin monotherapy or a basal insulin and one to three oral anti-diabetics alone selected from the group consisting of metformin, a sulfonylurea, a DPP-4 inhibitor or a glinide alone.
  • the basal insulin is in particular selected from insulin glargine, insulin detemir and isophane insulin (NPH insulin).
  • this type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the type 2 diabetes mellitus patient to be treated according to the present invention may have a fasting plasma glucose of at least 9 mmol/L or at least 9.5 mmol/L when treated with a basal insulin monotherapy or a basal insulin and one to three oral anti-diabetics alone selected from the group consisting of metformin, a sulfonylurea, a DPP-4 inhibitor or a glinide alone.
  • the patient may have this fasting plasma glucose of at least 9 mmol/L L or at least 9.5 mmol/L prior to the onset of therapy with the combination according to the present invention.
  • the basal insulin is in particular selected from insulin glargine, insulin detemir and isophane insulin (NPH insulin).
  • this type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the patient may have a fasting plasma glucose in the range of 5.6 to 6.9 mmol/L when treated with compound (b) and optionally compound (c) alone. This range can be considered to be an impaired fasting plasma glucose concentration.
  • the patient may have a fasting plasma glucose of at least 6.6 mmol/L, at least 6.7 mmol/L, at least 6.8 mmol/L or at least 6.9 mmol/L, when treated with compound (b) and optionally compound (c) alone.
  • the type 2 diabetes mellitus patient to be treated according to the present invention may have a HbA1c of at least 8.5% when treated with a basal insulin monotherapy or a basal insulin and one to three oral anti-diabetics alone selected from the group consisting of metformin, a sulfonylurea, a DPP-4 inhibitor or a glinide alone.
  • the patient may have this a HbA1c of at least 8.5% prior to the onset of therapy with the combination according to the present invention.
  • the basal insulin is in particular selected from insulin glargine, insulin detemir and isophane insulin (NPH insulin).
  • this type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the patient may have a HbA1c of at least 7.5% or at least 7.8% when treated with compound (b) and optionally compound (c) alone.
  • the patient to be treated according to the present invention does not receive concomitant treatment with at least one of a sulfonylurea, a DPP-4 inhibitor and a glinide.
  • the type 2 diabetes mellitus has been diagnosed for at least 1 year or at least 2 years prior to the onset of a therapy according to the present invention.
  • the administration of the combination according to the present invention can comprise the steps:
  • step (i) or/and (ii) wherein the amount of compound (b) to be administered in steps (i) or/and (ii) is adjusted (titrated) so that a predetermined fasting plasma glucose level or/and a predetermined self-monitored plasma glucose level is reached or at least approximated.
  • adjustment (titration) of compound (b) is performed in steps (i).
  • step (i) the compounds (b) and (c) of the pharmaceutical combination of the present invention may be administered for at least 4 weeks, at least 8 weeks, at least 12 weeks, or at least 16 weeks.
  • step (i) comprises administration of compounds (b) and (c) for at least about 12 weeks.
  • Step (i) may be performed for at the maximum about 8 weeks, at the maximum about 12 weeks, at the maximum about 16 weeks, at the maximum about 20 weeks, or at the maximum about 24 weeks. Preferred is a duration of step (i) of about 12 weeks.
  • Step (i) may be performed with the proviso that compound (a) is not administered.
  • a treatment with a combination of insulin glargine, lixisenatide and optionally metformin can improve fasting plasma glucose concentration, HbA 1c value, body weight and the risk of hypoglycemia if the treatment starts with administration of insulin glargine and optionally metformin alone.
  • the dose of insulin glargine can be reduced.
  • the amount of compound (b) to be administered in steps (i) or/and (ii) is adjusted so that a predetermined fasting plasma glucose level or/and a predetermined self-monitored plasma glucose level is reached or at least approximated.
  • the amount of compound (b) to be administered in steps (i) or/and (ii) may be adjusted on the basis of daily measurements of plasma glucose concentration.
  • the amount of compound (b) to be administered in steps (i) or/and (ii) may adjusted so that
  • SMPG Self-monitored plasma glucose
  • 4-point Self Monitored Plasma Glucose or the “7-point Self Monitored Plasma Glucose”.
  • the 4 point and 7-point Self Monitored Plasma Glucose value are in particular average plasma glucose concentrations including fasting and postprandial conditions.
  • “4-point Self Monitored Plasma Glucose” in particular refers to the measurement of plasma glucose four times a day and calculation of the average plasma glucose concentration therefrom.
  • the 4-point Self Monitored Plasma Glucose measurements are performed pre-breakfast, post-breakfast, pre-dinner, and post-dinner.
  • 7-point Self Monitored Plasma Glucose in particular refers to the measurement of plasma glucose seven times a day and calculation of the average plasma glucose concentration therefrom.
  • the 7-point Self Monitored Plasma Glucose measurements are performed pre-breakfast, post-breakfast, pre-lunch, post-lunch, pre-dinner, post-dinner and at bed-time.
  • the “fasting self-monitored plasma glucose (SMPG)”, as used herein, is measured by the patient before breakfast, in particular before insulin glargine or/and lixisenatide injection and optional intake of metformin.
  • a type 2 diabetes mellitus patient may have a HbA1c value in the range of 7% to 10%.
  • the type 2 diabetes mellitus patient to be treated may have a HbA 1c value of at least about 7%, at least about 7.5%, at least about 7.8%, at least about 8%, at least about 8.5%, or at least about 9%.
  • the type 2 diabetes mellitus patient to be treated according to the present invention may have a 2 hours postprandial plasma glucose concentration of at least 11.1 mmol/L, at least 12 mmol/L, at least 13 mmol/L, at least 13.5 mmol/L or at least 14 mmol/L. These plasma glucose concentrations exceed normoglycemic concentrations, indicating that the type 2 diabetes mellitus is not adequately controlled if treated with an antidiabetic compound, as described herein.
  • Postprandial is a term that is well known to a person skilled in the art of diabetology.
  • the term “postprandial” describes in particular the phase after an ingestion of a meal or/and exposure to glucose under experimental conditions. In a healthy person this phase is characterised by an increase and subsequent decrease in blood glucose concentration.
  • the postprandial phase typically ends up to 2 h after a meal or/and exposure to glucose (2 h postprandial plasma glucose concentration).
  • the type 2 diabetes mellitus patient to be treated according to the invention may have a fasting plasma glucose concentration of at least 8 mmol/L, at least 8.5 mmol/L, at least 9 mmol/L, or at least 9.5 mmol/L. These plasma glucose concentrations exceed normoglycemic concentrations, indicating that the type 2 diabetes mellitus is not adequately controlled if treated with an antidiabetic compound, as described herein.
  • metformin can be administered according to commonly known administration protocols of metformin in accordance with the terms of marketing authorization.
  • metformin can be administrated once daily, twice daily or three times a day.
  • the metformin dose applied before the onset of the therapy as disclosed herein is continued in combination with (a) lixisenatide or/and a pharmaceutically acceptable salt thereof, and (b) insulin glargine or/and a pharmaceutically acceptable salt thereof, as disclosed herein.
  • metformin may be administered orally.
  • Metformin may be administered to a type 2 diabetes mellitus patient in need thereof, in an amount sufficient to induce a therapeutic effect.
  • Metformin may be administered in a dose of at least 1.0 g/day or at least 1.5 g/day.
  • Metformin may be administered in a dose of at the maximum of 2.0 g/day or at the maximum of 3.5 g/day.
  • the daily metformin dose can be divided into two or three separate doses.
  • metformin may be formulated in a solid dosage form, such as a tablet or pill.
  • Metformin may be formulated with suitable pharmaceutically acceptable carriers, adjuvants, or/and auxiliary substances.
  • lixisenatide or/and a pharmaceutically acceptable salt may be administered in an add-on therapy to administration of insulin glargine and optionally metformin.
  • the terms “add-on”, “add-on treatment” and “add-on therapy” relate to treatment according to the present invention with insulin glargine and lixisenatide, and optionally metformin.
  • Metformin, insulin glargine or/and lixisenatide each may be administered in a once-a-day-dosage.
  • Metformin, insulin glargine and lixisenatide may be administered by different administration routes.
  • Metformin may be administered orally, and lixisenatide and insulin glargine may be administered parenterally.
  • additives mean that the dose of metformin administered before the onset of the treatment according to the present invention, as disclosed herein, can be continued in the treatment of the present invention.
  • lixisenatide includes pharmaceutically acceptable salts thereof.
  • suitable pharmaceutically acceptable salts of lixisenatide is the acetate salt of lixisenatide.
  • lixisenatide or/and the pharmaceutically acceptable salt thereof may be administered to a type 2 diabetes mellitus patient in need thereof, in an amount sufficient to induce a therapeutic effect.
  • lixisenatide or/and the pharmaceutically acceptable salt thereof may be formulated with suitable pharmaceutically acceptable carriers, adjuvants, or/and auxiliary substances.
  • Lixisenatide or/and a pharmaceutically acceptable salt thereof may be administered parenterally, e.g. by injection (such as by intramuscular or by subcutaneous injection). Suitable injection devices, for instance the so-called “pens” comprising a cartridge comprising the active ingredient, and an injection needle, are known. Lixisenatide or/and a pharmaceutically acceptable salt thereof may be administered in a suitable amount, for instance in an amount in the range of 10 ⁇ g to 20 ⁇ g per dose.
  • lixisenatide or/and a pharmaceutically acceptable salt thereof may be administered in a daily dose in the range of 10 ⁇ g to 20 ⁇ g.
  • Lixisenatide or/and a pharmaceutically acceptable salt thereof may be administered by one injection per day.
  • Lixisenatide or/and a pharmaceutically acceptable salt thereof may be administered about 30 min before breakfast.
  • lixisenatide or/and a pharmaceutically acceptable salt thereof may be provided in a liquid composition, which preferably is an aqueous formulation. It is preferred that the liquid composition is suitable for parenteral administration, in particular for injection.
  • a liquid composition of the present invention may have an acidic or a physiologic pH.
  • An acidic pH preferably is in the range of pH 1-6.8, pH 3.5-6.8, or pH 3.5-5.
  • a physiologic pH preferably is in the range of pH 2.5-8.5, pH 4.0-8.5, or pH 6.0-8.5.
  • the pH may be adjusted by a pharmaceutically acceptable diluted acid (typically HCl) or pharmaceutically acceptable diluted base (typically NaOH).
  • the liquid composition comprising lixisenatide or/and a pharmaceutically acceptable salt thereof may comprise a suitable preservative.
  • a suitable preservative may be selected from phenol, m-cresol, benzyl alcohol and p-hydroxybenzoic acid ester.
  • a preferred preservative is m-cresol.
  • the liquid composition comprising lixisenatide or/and a pharmaceutically acceptable salt thereof may comprise a tonicity agent.
  • a suitable tonicity agent may be selected from glycerol, lactose, sorbitol, mannitol, glucose, NaCl, calcium or magnesium containing compounds such as CaCl 2 .
  • the concentration of glycerol, lactose, sorbitol, mannitol and glucose may be in the range of 100-250 mM.
  • the concentration of NaCl may be up to 150 mM.
  • a preferred tonicity agent is glycerol.
  • the liquid composition comprising lixisenatide or/and a pharmaceutically acceptable salt thereof may comprise methionine from 0.5 ⁇ g/mL to 20 ⁇ g/mL, preferably from 1 ⁇ g/ml to 5 ⁇ g/ml.
  • the liquid composition comprises L-methionine.
  • insulin glargine or/and a pharmaceutically acceptable salt thereof may be provided in a liquid composition, which preferably is an aqueous formulation. It is preferred that the liquid composition is suitable for parenteral administration, in particular for injection. The skilled person knows such liquid compositions of insulin glargine.
  • Surfactants can be added to pharmaceutical formulation comprising insulin glargine, for example, inter alia, non-ionic surfactants.
  • pharmaceutically customary surfactants are preferred, such as, for example: partial and fatty acid esters and ethers of polyhydric alcohols such as of glycerol, sorbitol and the like (Span®, Tween®, in particular Tween® 20 and Tween® 80, Myrj®, Brij®), Cremophor® or poloxamers.
  • the surfactants are present in the pharmaceutical composition in a concentration of 5-200 ⁇ g/ml, preferably of 5-120 ⁇ g/ml and particularly preferably of 20-75 ⁇ g/ml.
  • the formulation comprising insulin glargine or/and a pharmaceutically acceptable salt thereof can additionally contain preservatives (e.g. phenol, m-cresol, p-cresol, parabens), isotonic agents (e.g. mannitol, sorbitol, lactose, dextrose, trehalose, sodium chloride, glycerol), buffer substances, salts, acids and alkalis and also further excipients. These substances can in each case be present individually or alternatively as mixtures.
  • preservatives e.g. phenol, m-cresol, p-cresol, parabens
  • isotonic agents e.g. mannitol, sorbitol, lactose, dextrose, trehalose, sodium chloride, glycerol
  • buffer substances e.g. mannitol, sorbitol, lactose, dextrose, trehalose, sodium chloride, g
  • Glycerol, dextrose, lactose, sorbitol and mannitol can be present in the pharmaceutical formulation comprising insulin glargine or/and a pharmaceutically acceptable salt thereof in a concentration of 100-250 mM, NaCI in a concentration of up to 150 mM.
  • Buffer substances such as, for example, phosphate, acetate, citrate, arginine, glycylglycine or TRIS (i.e. 2-amino-2-hydroxymethyl-1,3-propanediol) buffer and corresponding salts, can be present in a concentration of 5-250 mM, preferably 10-100 mM.
  • Further excipients can be, inter alia, salts or arginine.
  • the zinc concentration of the formulation comprising insulin glargine or/and a pharmaceutically acceptable salt thereof is in the range of the concentration which is reached by the presence of 0-1000 ⁇ g/mL, preferably 20-400 ⁇ g/mL zinc, most preferably 90 ⁇ g/mL.
  • the zinc may be present in form of zinc chloride, but the salt is not limited to be zinc chloride.
  • glycerol and/or mannitol can be present in a concentration of 100-250 mmol/L, and/or NaCl is preferably present in a concentration of up to 150 mmol/L.
  • a buffer substance can be present in a concentration of 5-250 mmol/L.
  • Insulin glargine or/and a pharmaceutically acceptable salt thereof can be present in the pharmaceutical formulation in a concentration of 60-6000 nmol/ml, preferably 240-3000 nmol/ml.
  • the pH of the formulation comprising insulin glargine or/and a pharmaceutically acceptable salt thereof can be in the range of pH 1-6.8, preferably pH 3.5-6.8, more preferred pH 3.5-4.5, even more preferred pH 4.0-4.5.
  • Yet another aspect of the present invention is the use of a combination comprising
  • the patient may be a patient as defined herein.
  • Yet another aspect of the present invention is the use of a combination comprising
  • the fasting plasma glucose or/and the 2 hour postprandial plasma glucose in a type 2 diabetes mellitus patient preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the patient may be a patient as defined herein.
  • Yet another aspect of the present invention is the use of a combination comprising
  • the patient may be a patient as defined herein.
  • Yet another aspect of the present invention is the use of a combination comprising
  • the patient may be a patient as defined herein.
  • Yet another aspect of the present invention is method for glycemic control in a type 2 diabetes mellitus patient, said method comprising administration of a combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the patient may be a patient as defined herein.
  • Yet another aspect of the present invention is method for the improvement of the HbA1c value, the fasting plasma glucose or/and the 2 hour postprandial plasma glucose in a type 2 diabetes mellitus patient, said method comprising administration the use of a combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the patient may be a patient as defined herein.
  • Yet another aspect of the present invention is method for the prevention of weight gain or/and for inducing weight loss in a type 2 diabetes mellitus patient, said method comprising administration the use of a combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the patient may be a patient as defined herein.
  • Yet another aspect of the present invention is method for the reduction of the risk of hypoglycemia in a type 2 diabetes mellitus patient, said method comprising administration the use of a combination comprising
  • the type 2 diabetes mellitus to be treated preferably is not adequately controlled with compound (b) and optionally compound (c) alone.
  • the patient may be a patient as defined herein.
  • FIG. 1 Plot of mean change in HbA1 c(%) from baseline by visit—mITT population
  • FIG. 2 Peak of mean change in body weight (kg) from baseline by visit—mITT population
  • FIG. 3 Plot of mean insulin glargine daily dose (U) by visit—mITT population
  • FIG. 4 Plot of mean daily insulin glulisine dose (U) by visit—mITT population
  • FIG. 5 Plot of mean total insulin dose (U) by visit—mITT population
  • FIG. 6 Graphical study design. 1 Insulin glargine should be injected subcutaneously once daily at dinner or breakfast time (according to patient's/investigators' preference). Injection time (dinner or breakfast) should be fixed at V2 and remain the same throughout the study. 2 Injection of lixisenatide should be performed 30-60 minutes prior to dinner or breakfast (the one associated with the highest self-monitored 2h-PPG median value across 3 different days). Meal used for lixisenatide dosing should remain the same throughout the 26-week treatment period. 3 Injection of insulin glulisine should be done 0 to 15 minutes before dinner or breakfast (the one associated with the highest self-monitored 2h-PPG median value across 3 different days). Meal used for insulin glulisine dosing should remain the same throughout the 26-week treatment period. 4 Injection of insulin glulisine prior to breakfast, lunch and dinner.
  • ECG Electrocardiogram
  • FPG Fasting plasma glucose
  • GLP-1 Glucagon-like peptide-1
  • TID Ter in die (Three times a day)
  • LOCF Last observation carried forward.
  • a Analysis of covariance (ANCOVA) model with treatment groups lixisenatide, insulin glulisine QD, and insulin glulisine TID
  • Visit 7 Wide ⁇ 1 strata of HbA1c [ ⁇ 8.0, ⁇ 8.0%], randomization strata of metformin use, and country as fixed effects and baseline HbA1c value as a covariate.
  • the analysis included measurements obtained up to 14 days after the last injection of the investigational medicinal product. Patients with both baseline and Week 26 (LOCF) measurements are included.
  • insulin glulisine QD or lixisenatide vs. insulin glulisine TID.
  • the analysis included measurements obtained up to 3 days after the last injection of the investigational medicinal product. Patients with both baseline and Week 26 (LOCF) measurements are included.
  • FIG. 1 shows the mean change in HbA1c(%) from baseline by visit in the mITT population.
  • FIG. 2 shows the mean change in body weight (kg) from baseline by visit in the mITT population.
  • LOCF Last observation carried forward.
  • a Analysis of covariance (ANCOVA) model with treatment groups lixisenatide, insulin glulisine QD, insulin glulisine TID
  • the analysis included measurements obtained up to one day after the last injection of the investigational medicinal product. Patients with both baseline and Week 26 (LOCF) measurements are included.
  • LOCF Last observation carried forward.
  • a Analysis of covariance (ANCOVA) model with treatment groups lixisenatide, insulin glulisine QD, insulin glulisine TID
  • the analysis included measurements obtained up to the date of the last injection of the investigational medicinal product. Patients with both baseline and Week 26 (LOCF) measurements are included.
  • FIG. 3 shows the mean insulin glargine daily dose (U) by visit in the mITT population.
  • FIG. 4 shows the mean daily insulin glulisine dose (U) by visit in the mITT population.
  • FIG. 5 shows the mean total insulin dose (U) by visit in the mITT population
  • On-treatment period the time from the first injection of the investigational medicinal product up to 3 days after the last injection of the investigational medicinal product. 1 Calculated as (number of patients with events * 100 divided by total exposure + 3 days in patient years). 2 Calculated as (number of events * 100 divided by total exposure + 3 days in patient years).
  • Co-primary endpoints at 26 weeks were (1) non-inferiority (95% CI upper bound ⁇ 0.4%) in HbA 1c reduction with LIXI vs GLU-1 and (2) for LIXI vs GLU-3, either non-inferiority in HbA 1c reduction (2a) OR superiority (one-sided ⁇ 0.025) in body weight change (2b).
  • FPG, PPG, IG dose, composite outcomes, AEs, and hypoglycemia were assessed.
  • Each arm randomized 298 pts (T2DM duration 12 yrs, BI duration 3 yrs, weight ⁇ 90 kg).
  • AEs adverse events
  • BL baseline
  • CI confidence interval
  • FPG fasting plasma glucose
  • HbA 1c glycated hemoglobin
  • LOCF last observation carried forward
  • LS least squares
  • mITT modified intent-to-treat
  • PPG postprandial glucose
  • QD once daily
  • SD standard deviation
  • SE standard error
  • TID thrice daily.
  • n numbers are for the mITT population (all pts who received ⁇ 1 dose of study medication, with both a baseline assessment and ⁇ 1 post-baseline assessment).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
US15/068,286 2015-03-13 2016-03-11 Treatment Type 2 Diabetes Mellitus Patients Abandoned US20160287674A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/646,760 US10434147B2 (en) 2015-03-13 2017-07-11 Treatment type 2 diabetes mellitus patients

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP15159064.3 2015-03-13
EP15159064 2015-03-13

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/646,760 Division US10434147B2 (en) 2015-03-13 2017-07-11 Treatment type 2 diabetes mellitus patients

Publications (1)

Publication Number Publication Date
US20160287674A1 true US20160287674A1 (en) 2016-10-06

Family

ID=52684082

Family Applications (2)

Application Number Title Priority Date Filing Date
US15/068,286 Abandoned US20160287674A1 (en) 2015-03-13 2016-03-11 Treatment Type 2 Diabetes Mellitus Patients
US15/646,760 Active US10434147B2 (en) 2015-03-13 2017-07-11 Treatment type 2 diabetes mellitus patients

Family Applications After (1)

Application Number Title Priority Date Filing Date
US15/646,760 Active US10434147B2 (en) 2015-03-13 2017-07-11 Treatment type 2 diabetes mellitus patients

Country Status (22)

Country Link
US (2) US20160287674A1 (enExample)
EP (1) EP3268029B1 (enExample)
JP (1) JP6857129B2 (enExample)
KR (1) KR102694473B1 (enExample)
CN (1) CN107921099A (enExample)
AR (1) AR103914A1 (enExample)
AU (1) AU2016232448C1 (enExample)
CA (1) CA2979448A1 (enExample)
CL (1) CL2017002293A1 (enExample)
EA (1) EA034940B1 (enExample)
ES (1) ES2922551T3 (enExample)
IL (1) IL254496B (enExample)
MA (1) MA42287B1 (enExample)
MX (1) MX389091B (enExample)
NZ (1) NZ736299A (enExample)
PH (1) PH12017501662A1 (enExample)
PL (1) PL3268029T3 (enExample)
PT (1) PT3268029T (enExample)
SG (1) SG11201707372YA (enExample)
TN (1) TN2017000373A1 (enExample)
TW (1) TWI748945B (enExample)
WO (1) WO2016146514A1 (enExample)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10117909B2 (en) 2008-10-17 2018-11-06 Sanofi-Aventis Deutschland Gmbh Combination of an insulin and a GLP-1 agonist
US10159713B2 (en) 2015-03-18 2018-12-25 Sanofi-Aventis Deutschland Gmbh Treatment of type 2 diabetes mellitus patients
US10434147B2 (en) 2015-03-13 2019-10-08 Sanofi-Aventis Deutschland Gmbh Treatment type 2 diabetes mellitus patients
US12186374B2 (en) 2014-12-12 2025-01-07 Sanofi-Aventis Deutschland Gmbh Insulin glargine/lixisenatide fixed ratio formulation
US12303598B2 (en) 2009-11-13 2025-05-20 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition comprising a GLP-1-agonist and methionine

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102037996B1 (ko) 2018-03-22 2019-10-29 이화여자대학교 산학협력단 편도 유래 중간엽 줄기세포 또는 이의 조정 배지를 포함하는 제2형 당뇨병 예방 또는 치료용 조성물
KR20200132550A (ko) 2019-05-17 2020-11-25 이화여자대학교 산학협력단 편도 유래 중간엽 줄기세포 또는 이의 조정 배지를 포함하는 혈관질환 예방 또는 치료용 조성물
KR20190122196A (ko) 2019-10-22 2019-10-29 이화여자대학교 산학협력단 편도 유래 중간엽 줄기세포 또는 이의 조정 배지를 포함하는 제2형 당뇨병 예방 또는 치료용 조성물

Family Cites Families (408)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB835638A (en) 1956-12-01 1960-05-25 Novo Terapeutisk Labor As Insulin crystal suspensions having a protracted effect
GB840870A (en) 1957-08-03 1960-07-13 Novo Terapeutisk Labor As Improvements in or relating to insulin preparations
US3868358A (en) 1971-04-30 1975-02-25 Lilly Co Eli Protamine-insulin product
US3758683A (en) 1971-04-30 1973-09-11 R Jackson Insulin product
GB1554157A (en) 1975-06-13 1979-10-17 Takeda Chemical Industries Ltd Stable insulin preparation for intra nasal administration
US4153689A (en) 1975-06-13 1979-05-08 Takeda Chemical Industries, Ltd. Stable insulin preparation for nasal administration
GB1527605A (en) 1975-08-20 1978-10-04 Takeda Chemical Industries Ltd Insulin preparation for intranasal administration
US4165370A (en) 1976-05-21 1979-08-21 Coval M L Injectable gamma globulin
JPS6033474B2 (ja) 1978-05-11 1985-08-02 藤沢薬品工業株式会社 新規なヒアルロニダ−ゼｂｍｐ−８２３１およびその製造法
US4783441A (en) 1979-04-30 1988-11-08 Hoechst Aktiengesellschaft Aqueous protein solutions stable to denaturation
EP0018609B1 (de) 1979-04-30 1983-09-21 Hoechst Aktiengesellschaft Gegen Denaturierung beständige, wässrige Protein-Lösungen, Verfahren zu ihrer Herstellung und ihre Verwendung
JPS55153712A (en) 1979-05-18 1980-11-29 Kao Corp Insulin pharmaceutical preparation and its production
DE3033127A1 (de) 1980-09-03 1982-04-08 Hoechst Ag, 6000 Frankfurt Neue analoga des insulins
US4367737A (en) 1981-04-06 1983-01-11 George Kozam Multiple barrel syringe
JPS58501125A (ja) 1981-07-17 1983-07-14 ノルデイスク・インスリンラボラトリウム 安定な水性治療性インシユリン製剤及びその製造方法
NL193099C (nl) 1981-10-30 1998-11-03 Novo Industri As Gestabiliseerde insuline-oplossing.
DE3326472A1 (de) 1983-07-22 1985-02-14 Hoechst Ag, 6230 Frankfurt Neue insulin-derivate, verfahren zu deren herstellung und deren verwendung sowie pharmazeutische mittel zur behandlung des diabetes mellitus
DE3326473A1 (de) 1983-07-22 1985-01-31 Hoechst Ag, 6230 Frankfurt Pharmazeutisches mittel zur behandlung des diabetes mellitus
DE3327709A1 (de) 1983-07-29 1985-02-07 Hoechst Ag, 6230 Frankfurt Insulin-derivat-kristallsuspensionen, verfahren zu deren herstellung und deren verwendung
DE3333640A1 (de) 1983-09-17 1985-04-25 Hoechst Ag, 6230 Frankfurt Verfahren zur herstellung von insulin-derivaten, deren b-kette c-terminal verlaengert ist, neue basisch modifizierte insulin-derivate diese enthaltende mittel und ihre verwendung
CA1244347A (en) 1984-05-29 1988-11-08 Eddie H. Massey Stabilized insulin formulations
US4839341A (en) 1984-05-29 1989-06-13 Eli Lilly And Company Stabilized insulin formulations
EP0166971B1 (de) 1984-06-09 1990-02-28 Hoechst Aktiengesellschaft Insulinzubereitungen, Verfahren zu deren Herstellung und deren Verwendung
DE3440988A1 (de) 1984-11-09 1986-07-10 Hoechst Ag, 6230 Frankfurt Verfahren zur spaltung von peptiden und proteinen an der methionyl-bindung
DK113585D0 (da) 1985-03-12 1985-03-12 Novo Industri As Nye peptider
US5008241A (en) 1985-03-12 1991-04-16 Novo Nordisk A/S Novel insulin peptides
DK347086D0 (da) 1986-07-21 1986-07-21 Novo Industri As Novel peptides
CA1274774A (en) 1985-04-15 1990-10-02 Kenneth S. Su Method for administering insulin
US4689042A (en) 1985-05-20 1987-08-25 Survival Technology, Inc. Automatic medicament ingredient mixing and injecting apparatus
DE3526995A1 (de) 1985-07-27 1987-02-05 Hoechst Ag Fusionsproteine, verfahren zu ihrer herstellung und ihre verwendung
PH25772A (en) 1985-08-30 1991-10-18 Novo Industri As Insulin analogues, process for their preparation
US4960702A (en) 1985-09-06 1990-10-02 Codon Methods for recovery of tissue plasminogen activator
DE3636903A1 (de) 1985-12-21 1987-07-02 Hoechst Ag Fusionsproteine mit eukaryotischem ballastanteil
DE3541856A1 (de) 1985-11-27 1987-06-04 Hoechst Ag Eukaryotische fusionsproteine, ihre herstellung und verwendung sowie mittel zur durchfuehrung des verfahrens
US5496924A (en) 1985-11-27 1996-03-05 Hoechst Aktiengesellschaft Fusion protein comprising an interleukin-2 fragment ballast portion
CA1275922C (en) 1985-11-28 1990-11-06 Harunobu Amagase Treatment of cancer
DE3544295A1 (de) 1985-12-14 1987-06-19 Bayer Ag Thermoplastische formmassen mit hoher kriechstromfestigkeit
US5614492A (en) 1986-05-05 1997-03-25 The General Hospital Corporation Insulinotropic hormone GLP-1 (7-36) and uses thereof
PH23446A (en) 1986-10-20 1989-08-07 Novo Industri As Peptide preparations
ES2053723T3 (es) 1987-02-25 1994-08-01 Novo Nordisk As Nuevos derivados de insulina.
US5034415A (en) 1987-08-07 1991-07-23 Century Laboratories, Inc. Treatment of diabetes mellitus
DE3726655A1 (de) 1987-08-11 1989-02-23 Hoechst Ag Verfahren zur isolierung basischer proteine aus proteingemischen, welche solche basischen proteine enthalten
DK257988D0 (da) 1988-05-11 1988-05-11 Novo Industri As Nye peptider
US6875589B1 (en) 1988-06-23 2005-04-05 Hoechst Aktiengesellschaft Mini-proinsulin, its preparation and use
DE3827533A1 (de) 1988-08-13 1990-02-15 Hoechst Ag Pharmazeutische zubereitung zur behandlung des diabetes mellitus
US4923162A (en) 1988-09-19 1990-05-08 Fleming Matthew C Radiation shield swivel mount
DE3837825A1 (de) 1988-11-08 1990-05-10 Hoechst Ag Neue insulinderivate, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung
US5225323A (en) 1988-11-21 1993-07-06 Baylor College Of Medicine Human high-affinity neurotransmitter uptake system
WO1990007522A1 (en) 1988-12-23 1990-07-12 Novo Nordisk A/S Human insulin analogues
US4994439A (en) 1989-01-19 1991-02-19 California Biotechnology Inc. Transmembrane formulations for drug administration
US5514646A (en) 1989-02-09 1996-05-07 Chance; Ronald E. Insulin analogs modified at position 29 of the B chain
IL93282A (en) 1989-02-09 1995-08-31 Lilly Co Eli Insulin analogues
DK134189D0 (da) 1989-03-20 1989-03-20 Nordisk Gentofte Insulinforbindelser
ATE133087T1 (de) 1989-05-04 1996-02-15 Southern Res Inst Einkapselungsverfahren
US5358857A (en) 1989-08-29 1994-10-25 The General Hospital Corp. Method of preparing fusion proteins
IL95495A (en) 1989-08-29 1996-10-16 Hoechst Ag Fusion proteins their preparation and use
US5227293A (en) 1989-08-29 1993-07-13 The General Hospital Corporation Fusion proteins, their preparation and use
US5545618A (en) 1990-01-24 1996-08-13 Buckley; Douglas I. GLP-1 analogs useful for diabetes treatment
CN1020944C (zh) 1990-01-30 1993-05-26 阿图尔-费希尔股份公司费希尔厂 紧固件
US5397771A (en) 1990-05-10 1995-03-14 Bechgaard International Research And Development A/S Pharmaceutical preparation
ATE164080T1 (de) 1990-05-10 1998-04-15 Bechgaard Int Res Pharmazeutische zubereitung enthaltend n- glykofurole und n-äthylenglykole
DK155690D0 (da) 1990-06-28 1990-06-28 Novo Nordisk As Nye peptider
DK10191D0 (da) 1991-01-22 1991-01-22 Novo Nordisk As Hidtil ukendte peptider
US5272135A (en) 1991-03-01 1993-12-21 Chiron Ophthalmics, Inc. Method for the stabilization of methionine-containing polypeptides
CA2038597A1 (en) 1991-03-19 1992-09-20 Jose P. Garzaran A method and a pharmaceutical preparation for treating pain
US5614219A (en) 1991-12-05 1997-03-25 Alfatec-Pharma Gmbh Oral administration form for peptide pharmaceutical substances, in particular insulin
US6468959B1 (en) 1991-12-05 2002-10-22 Alfatec-Pharm Gmbh Peroral dosage form for peptide containing medicaments, in particular insulin
CH682806A5 (de) 1992-02-21 1993-11-30 Medimpex Ets Injektionsgerät.
CH682805A5 (de) 1992-02-24 1993-11-30 Medimpex Ets Anzeigeeinrichtung für ein Injektionsgerät.
DK36392D0 (da) 1992-03-19 1992-03-19 Novo Nordisk As Anvendelse af kemisk forbindelse
US5846747A (en) 1992-03-25 1998-12-08 Novo Nordisk A/S Method for detecting glucagon-like peptide-1 antagonists and agonists
DK39892D0 (da) 1992-03-25 1992-03-25 Bernard Thorens Peptid
US5253785A (en) 1992-04-02 1993-10-19 Habley Medical Technology Corp. Variable proportion dispenser
DK0600372T3 (da) 1992-12-02 1997-08-11 Hoechst Ag Fremgangsmåde til fremstilling af proinsulin med korrekt forbundne cystinbroer.
HUT71583A (en) 1992-12-18 1995-12-28 Lilly Co Eli Insulin-analogs
US5358708A (en) 1993-01-29 1994-10-25 Schering Corporation Stabilization of protein formulations
US5478323A (en) 1993-04-02 1995-12-26 Eli Lilly And Company Manifold for injection apparatus
US5424286A (en) 1993-05-24 1995-06-13 Eng; John Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same
AU6995794A (en) 1993-06-21 1995-01-17 Novo Nordisk A/S Aspb28 insulin crystals
US5506203C1 (en) 1993-06-24 2001-02-06 Astra Ab Systemic administration of a therapeutic preparation
US5534488A (en) 1993-08-13 1996-07-09 Eli Lilly And Company Insulin formulation
JPH09505308A (ja) 1993-11-19 1997-05-27 アルカーミズ・コントロールド・セラピューティクス・インコーポレイテッド・トゥー 生物学的活性剤を含有する生分解性微粒子の製造
US5705483A (en) 1993-12-09 1998-01-06 Eli Lilly And Company Glucagon-like insulinotropic peptides, compositions and methods
IT1265271B1 (it) 1993-12-14 1996-10-31 Alcatel Italia Sistema di predistorsione in banda base per la linearizzazione adattativa di amplificatori di potenza
US5595756A (en) 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
DE4405179A1 (de) 1994-02-18 1995-08-24 Hoechst Ag Verfahren zur Gewinnung von Insulin mit korrekt verbundenen Cystinbrücken
DE4405388A1 (de) 1994-02-19 1995-08-24 Hoechst Ag Verfahren zur Herstellung von Polyalkyl-1-oxa-diazaspirodecan-Verbindungen
JPH10501519A (ja) 1994-03-07 1998-02-10 インヘイル・セラピューティック・システムズ インシュリンを肺に送給できる方法および組成物
US5474978A (en) 1994-06-16 1995-12-12 Eli Lilly And Company Insulin analog formulations
US5559094A (en) 1994-08-02 1996-09-24 Eli Lilly And Company AspB1 insulin analogs
CA2196184C (en) 1994-09-09 2009-06-09 Yasutaka Igari Sustained release preparation containing metal salt of a peptide
US5879584A (en) 1994-09-10 1999-03-09 The Procter & Gamble Company Process for manufacturing aqueous compositions comprising peracids
US5547929A (en) 1994-09-12 1996-08-20 Eli Lilly And Company Insulin analog formulations
US5766582A (en) 1994-10-11 1998-06-16 Schering Corporation Stable, aqueous alfa interferon solution formulations
US5707641A (en) 1994-10-13 1998-01-13 Pharmaderm Research & Development Ltd. Formulations comprising therapeutically-active proteins or polypeptides
AR002976A1 (es) 1995-03-31 1998-05-27 Lilly Co Eli Formulaciones farmaceuticas parenterales de efecto prolongado de insulina; cristales de dichos analogos aplicables en dichas formulaciones yprocedimiento de las formulaciones mencionadas
US5990077A (en) 1995-04-14 1999-11-23 1149336 Ontario Inc. Glucagon-like peptide-2 and its therapeutic use
IL118127A0 (en) 1995-05-05 1996-09-12 Lilly Co Eli Single chain insulin with high bioactivity
US5824638A (en) 1995-05-22 1998-10-20 Shire Laboratories, Inc. Oral insulin delivery
US6143718A (en) 1995-06-07 2000-11-07 Amylin Pharmaceuticals, Inc. Treatment of Type II diabetes mellutis with amylin agonists
JP2002514892A (ja) 1995-06-08 2002-05-21 コブラ セラピューティクス リミテッド 遺伝子治療における合成ウイルス様粒子の使用
WO1997001331A2 (en) 1995-06-27 1997-01-16 Takeda Chemical Industries, Ltd. Method of producing sustained-release preparation
JPH11292787A (ja) 1995-08-15 1999-10-26 Asahi Chem Ind Co Ltd 生理活性ペプチドを含有する経粘膜投与製剤
DE19545257A1 (de) 1995-11-24 1997-06-19 Schering Ag Verfahren zur Herstellung von morphologisch einheitlichen Mikrokapseln sowie nach diesem Verfahren hergestellte Mikrokapseln
US5985309A (en) 1996-05-24 1999-11-16 Massachusetts Institute Of Technology Preparation of particles for inhalation
DE19637230A1 (de) 1996-09-13 1998-03-19 Boehringer Mannheim Gmbh Exendin-Analoga, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel
DE59712555D1 (de) 1996-06-05 2006-04-06 Roche Diagnostics Gmbh Exendin-analoga, verfahren zu deren herstellung und diese enthaltende arzneimittel
JP4472027B2 (ja) 1996-06-20 2010-06-02 ノボ ノルディスク アクティーゼルスカブ 炭水化物含有インスリン製剤
IL127366A0 (en) 1996-06-20 1999-10-28 Novo Nordisk As Insulin preparations containing NaCl
US5948751A (en) 1996-06-20 1999-09-07 Novo Nordisk A/S X14-mannitol
US6110703A (en) 1996-07-05 2000-08-29 Novo Nordisk A/S Method for the production of polypeptides
EP0966297B2 (en) 1996-08-08 2013-02-27 Amylin Pharmaceuticals, Inc. Regulation of gastrointestinal motility
AU752411B2 (en) 1996-08-13 2002-09-19 Genentech Inc. Formulation
US5783556A (en) 1996-08-13 1998-07-21 Genentech, Inc. Formulated insulin-containing composition
US6268343B1 (en) 1996-08-30 2001-07-31 Novo Nordisk A/S Derivatives of GLP-1 analogs
US6006753A (en) 1996-08-30 1999-12-28 Eli Lilly And Company Use of GLP-1 or analogs to abolish catabolic changes after surgery
JP3149958B2 (ja) 1996-08-30 2001-03-26 ノボ ノルディスク アクティーゼルスカブ Ｇｌｐ―１誘導体
US6277819B1 (en) 1996-08-30 2001-08-21 Eli Lilly And Company Use of GLP-1 or analogs in treatment of myocardial infarction
UA65549C2 (uk) 1996-11-05 2004-04-15 Елі Ліллі Енд Компані Спосіб регулювання ожиріння шляхом периферійного введення аналогів та похідних glp-1 (варіанти) та фармацевтична композиція
WO1998030231A1 (en) 1997-01-07 1998-07-16 Amylin Pharmaceuticals, Inc. Use of exendins and agonists thereof for the reduction of food intake
US7312196B2 (en) 1997-01-08 2007-12-25 Amylin Pharmaceuticals, Inc. Formulations for amylin agonist peptides
US6410511B2 (en) 1997-01-08 2002-06-25 Amylin Pharmaceuticals, Inc. Formulations for amylin agonist peptides
EP0981611A1 (en) 1997-02-05 2000-03-01 1149336 Ontario Inc. Polynucleotides encoding proexendin, and methods and uses thereof
US5846937A (en) 1997-03-03 1998-12-08 1149336 Ontario Inc. Method of using exendin and GLP-1 to affect the central nervous system
US6310038B1 (en) 1997-03-20 2001-10-30 Novo Nordisk A/S Pulmonary insulin crystals
US6043214A (en) 1997-03-20 2000-03-28 Novo Nordisk A/S Method for producing powder formulation comprising an insulin
AU742591B2 (en) 1997-03-20 2002-01-10 Novo Nordisk A/S Zinc free insulin crystals for use in pulmonary compositions
ZA984697B (en) 1997-06-13 1999-12-01 Lilly Co Eli Stable insulin formulations.
ES2190087T3 (es) 1997-06-13 2003-07-16 Genentech Inc Formulacion estabilizada de un anticuerpo.
DE19726167B4 (de) 1997-06-20 2008-01-24 Sanofi-Aventis Deutschland Gmbh Insulin, Verfahren zu seiner Herstellung und es enthaltende pharmazeutische Zubereitung
AU749914B2 (en) 1997-08-08 2002-07-04 Amylin Pharmaceuticals, Inc. Novel exendin agonist compounds
DE19735711C2 (de) 1997-08-18 2001-04-26 Aventis Pharma Gmbh Verfahren zur Herstellung eines Vorläufers von Insulin oder Insulinderivaten mit korrekt verbundenen Cystinbrücken
BR9813111A (pt) 1997-10-24 2000-08-15 Lilly Co Eli Composições de insulina insolúveis
US6444641B1 (en) 1997-10-24 2002-09-03 Eli Lilly Company Fatty acid-acylated insulin analogs
ZA989744B (en) 1997-10-31 2000-04-26 Lilly Co Eli Method for administering acylated insulin.
CA2309955A1 (en) 1997-11-12 1999-05-20 Alza Corporation Method for decreasing self-association of polypeptides
CA2309356C (en) 1997-11-14 2010-09-21 Amylin Pharmaceuticals, Inc. Novel exendin agonist compounds
WO1999025727A2 (en) 1997-11-14 1999-05-27 Amylin Pharmaceuticals, Inc. Novel exendin agonist compounds
WO1999029336A1 (en) 1997-12-05 1999-06-17 Eli Lilly And Company Glp-1 formulations
DE69924232D1 (de) 1998-01-09 2005-04-21 Novo Nordisk As Stabilisierte insulin-zubereitungen
DE69936446T2 (de) 1998-02-13 2008-03-06 Amylin Pharmaceuticals, Inc., San Diego Inotropische und diuretische effekte von exendin und glp-1
ID26788A (id) 1998-02-23 2001-02-08 Neurocrine Biosciences Inc Metoda pengobatan diabetes dengan menggunakan analogi peptida dari insulin
JP2003522099A (ja) 1998-02-27 2003-07-22 ノボ ノルディスク アクティーゼルスカブ 遅延作用プロファイルを有するｇｌｐ−１のｇｌｐ−１誘導体及びエキセンジン
IL138214A0 (en) 1998-03-09 2001-10-31 Zealand Pharmaceuticals As Pharmacolgically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis
DE69918070T2 (de) 1998-03-13 2005-08-25 Novo Nordisk A/S Stabilisierte, wässrige Glukagonlösungen, enthaltend Detergenzien
JP2002516880A (ja) 1998-06-05 2002-06-11 テクニオン リサーチ アンド デベロップメント ファウンデーション リミテッド インスリンを補った乳児用調製乳
JP2002526554A (ja) 1998-10-07 2002-08-20 メディカル カレッジ オブ ジョージア リサーチ インスティチュート，インコーポレイテッド 骨親和性ホルモンとして用いられるグルコース依存性インスリン親和性ペプチド
US6284725B1 (en) 1998-10-08 2001-09-04 Bionebraska, Inc. Metabolic intervention with GLP-1 to improve the function of ischemic and reperfused tissue
US6211144B1 (en) 1998-10-16 2001-04-03 Novo Nordisk A/S Stable concentrated insulin preparations for pulmonary delivery
JP2002527488A (ja) 1998-10-16 2002-08-27 ノボ ノルディスク アクティーゼルスカブ メントールを含有する肺送達のためのインスリン製剤
EP1121144B1 (en) 1998-10-16 2002-06-05 Novo Nordisk A/S Stable concentrated insulin preparations for pulmonary delivery
EP1131089B1 (en) 1998-11-18 2004-02-18 Novo Nordisk A/S Stable aqueous insulin preparations without phenol and cresol
US6489292B1 (en) 1998-11-18 2002-12-03 Novo Nordisk A/S Stable aqueous insulin preparations without phenol and cresol
DK1140145T4 (da) 1999-01-14 2019-07-22 Amylin Pharmaceuticals Llc Hidtil ukendte exendinagonistformuleringer og fremgangsmåder til indgivelse deraf
DE19908041A1 (de) 1999-02-24 2000-08-31 Hoecker Hartwig Kovalent verbrückte Insulindimere
US6248363B1 (en) 1999-11-23 2001-06-19 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
JP2000247903A (ja) 1999-03-01 2000-09-12 Chugai Pharmaceut Co Ltd 長期安定化製剤
JP2007204498A (ja) 1999-03-01 2007-08-16 Chugai Pharmaceut Co Ltd 長期安定化製剤
US6227819B1 (en) 1999-03-29 2001-05-08 Walbro Corporation Fuel pumping assembly
US6271241B1 (en) 1999-04-02 2001-08-07 Neurogen Corporation Cycloalkyl and aryl fused aminoalkyl-imidazole derivatives: modulators and GLP-1 receptors
CA2372214A1 (en) 1999-04-30 2000-11-09 Amylin Pharmaceuticals, Inc. Modified exendins and exendin agonists
DK1180121T3 (da) 1999-05-17 2004-03-01 Conjuchem Inc Langtidsvirkende insulinotrope peptider
US6978471B1 (en) 1999-05-25 2005-12-20 Thomson Licensing S.A. System for acquiring and processing broadcast programs and program guide data
JP2003501404A (ja) 1999-06-04 2003-01-14 デルルックス ファーマシューティカル コーポレイション 薬剤の脱水粒子からなる製剤およびこれの調製方法
US6344180B1 (en) 1999-06-15 2002-02-05 Bionebraska, Inc. GLP-1 as a diagnostic test to determine β-cell function and the presence of the condition of IGT and type II diabetes
EP1196189A2 (en) 1999-06-25 2002-04-17 Medtronic MiniMed, Inc. Multiple agent diabetes therapy
US6309663B1 (en) 1999-08-17 2001-10-30 Lipocine Inc. Triglyceride-free compositions and methods for enhanced absorption of hydrophilic therapeutic agents
DE19930631A1 (de) 1999-07-02 2001-01-11 Clemens Micheler Spritzvorrichtung zur Injektion mindestens zweier flüssiger Therapeutika, insbesondere Insuline
EP1076066A1 (en) 1999-07-12 2001-02-14 Zealand Pharmaceuticals A/S Peptides for lowering blood glucose levels
US6528486B1 (en) 1999-07-12 2003-03-04 Zealand Pharma A/S Peptide agonists of GLP-1 activity
CN1174741C (zh) 1999-09-21 2004-11-10 Rtp药品公司 生物活性物质的表面改性微粒组合物
DE19947456A1 (de) 1999-10-02 2001-04-05 Aventis Pharma Gmbh C-Peptid zur verbesserten Herstellung von Insulin und Insulinanaloga
CN1245216C (zh) 1999-10-04 2006-03-15 希龙公司 稳定化的含多肽的液体药物组合物
US6720001B2 (en) 1999-10-18 2004-04-13 Lipocine, Inc. Emulsion compositions for polyfunctional active ingredients
PL199278B1 (pl) 1999-11-03 2008-09-30 Bristol Myers Squibb Co Zastosowanie metforminy i gliburydu
US7022674B2 (en) 1999-12-16 2006-04-04 Eli Lilly And Company Polypeptide compositions with improved stability
EP1523993A1 (en) 1999-12-16 2005-04-20 Eli Lilly & Company Polypeptide compositions with improved stability
JP2003523972A (ja) 1999-12-16 2003-08-12 イーライ・リリー・アンド・カンパニー 安定性が改良されたポリペプチド組成物
US20010012829A1 (en) 2000-01-11 2001-08-09 Keith Anderson Transepithelial delivery GLP-1 derivatives
EP1250126A2 (en) 2000-01-11 2002-10-23 Novo Nordisk A/S Transepithelial delivery of glp-1 derivatives
WO2001052937A1 (en) 2000-01-24 2001-07-26 Medtronic Minimed, Inc. Mixed buffer system for stabilizing polypeptide formulations
US6395767B2 (en) 2000-03-10 2002-05-28 Bristol-Myers Squibb Company Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method
AU2001264789A1 (en) 2000-06-08 2001-12-17 Eli Lilly And Company Protein powder for pulmonary delivery
US6689353B1 (en) 2000-06-28 2004-02-10 Bayer Pharmaceuticals Corporation Stabilized interleukin 2
WO2002004481A2 (en) 2000-07-12 2002-01-17 Eli Lilly And Company Process to increase protein stability
DK1326630T3 (da) 2000-09-18 2008-09-15 Sanos Bioscience As Anvendelse af GLP-2-peptider
KR100508695B1 (ko) 2001-02-13 2005-08-17 한국과학기술연구원 인슐린의 경구투여용 제형과 그의 제조방법
US7060675B2 (en) 2001-02-15 2006-06-13 Nobex Corporation Methods of treating diabetes mellitus
DE10108211A1 (de) 2001-02-20 2002-08-22 Aventis Pharma Gmbh Verwendung von Fusionsproteinen, deren N-terminaler Anteil aus einem Hirudinderivat besteht, zur Herstellung rekombinanter Proteine über Sekretion durch Hefen
DE10108100A1 (de) 2001-02-20 2002-08-29 Aventis Pharma Gmbh Verwendung supersekretierbarer Peptide in Verfahren zu deren Herstellung und paralleler Verbesserung der Exportate eines oder mehrerer anderer Polypeptide von Interesse
DE10108212A1 (de) 2001-02-20 2002-08-22 Aventis Pharma Gmbh Fusionsprotein zur Sekretion von Wertprotein in bakterielle Überstände
AU2002248464A1 (en) 2001-02-21 2002-09-12 Medtronic Minimed, Inc. Stabilized insulin formulations
AU2002258428A1 (en) 2001-02-26 2002-09-12 Millennium Pharmaceuticals, Inc. Methods for the treatment of metabolic disorders, including obesity and diabetes
DE10114178A1 (de) 2001-03-23 2002-10-10 Aventis Pharma Gmbh Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität
EP1377608B1 (en) 2001-04-02 2009-09-16 Novo Nordisk A/S Insulin precursors and a process for their preparation
CN1160122C (zh) 2001-04-20 2004-08-04 清华大学 一种制备口服胰岛素油相制剂的方法
US20030026872A1 (en) 2001-05-11 2003-02-06 The Procter & Gamble Co. Compositions having enhanced aqueous solubility and methods of their preparation
US6737401B2 (en) 2001-06-28 2004-05-18 Metronic Minimed, Inc. Methods of evaluating protein formulation stability and surfactant-stabilized insulin formulations derived therefrom
US7156877B2 (en) 2001-06-29 2007-01-02 The Regents Of The University Of California Biodegradable/bioactive nucleus pulposus implant and method for treating degenerated intervertebral discs
FR2827604B1 (fr) 2001-07-17 2003-09-19 Sanofi Synthelabo Nouveaux derives de 1-phenylsulfonyl-1,3-dihydro-2h-indol-2- one, un procede pour leur preparation et les compositions pharmaceutiques en contenant
EP2022505B1 (en) 2001-07-31 2011-12-14 The Government of the United States of America, as represented by the Secretary of the Department of Health and Human Services GLP-1, exendin-4, peptide analogs and uses thereof
CN1635900A (zh) 2001-08-28 2005-07-06 伊莱利利公司 Glp－1和基础胰岛素的预混合物
WO2003035028A1 (en) 2001-10-19 2003-05-01 Nektar Therapeutics Modulating charge density to produce improvements in the characteristics of spray-dried proteins
AU2002335046A1 (en) 2001-10-19 2003-05-06 Inhale Therapeutic Systems, Inc. The use of proton sequestering agents in drug formulations
CN100424179C (zh) 2001-11-19 2008-10-08 诺沃挪第克公司 制备胰岛素化合物的方法
WO2003053363A2 (en) 2001-12-19 2003-07-03 Millennium Pharmaceuticals, Inc. Human diacylglycerol acyltransferase 2 (dgat2) family members and uses therefor
EP1545460A4 (en) 2001-12-20 2005-11-16 Lilly Co Eli INSULIN MOLECULE WITH TEMPORARY EFFECT
BR0215216A (pt) 2001-12-21 2004-11-16 Novo Nordisk Healthcare Ag Composição aquosa lìquida, método para preparar uma composição aquosa lìquida de um polipeptìdeo de fator vii, uso de uma composição aquosa lìquida, e, método para o tratamento de uma sìndrome de resposta ao fator vii
US8058233B2 (en) 2002-01-10 2011-11-15 Oregon Health And Science University Modification of feeding behavior using PYY and GLP-1
AU2003203146A1 (en) 2002-02-07 2003-09-02 Novo Nordisk A/S Use of glp-1 compound for treatment of critically ill patients
US20100069293A1 (en) 2002-02-27 2010-03-18 Pharmain Corporation Polymeric carrier compositions for delivery of active agents, methods of making and using the same
TWI351278B (en) 2002-03-01 2011-11-01 Nisshin Pharma Inc Agent for preventing and treating of liver disease
TW200810743A (en) * 2002-03-22 2008-03-01 Novartis Ag Combination of organic compounds
EP1506003A1 (en) 2002-05-07 2005-02-16 Novo Nordisk A/S Soluble formulations comprising insulin aspart and insulin detemir
EP1506230B1 (en) 2002-05-07 2011-01-19 Novo Nordisk A/S Soluble formulations comprising monomeric insulin and acylated insulin
US7115563B2 (en) 2002-05-29 2006-10-03 Insignion Holding Limited Composition and its therapeutic use
US20040022792A1 (en) 2002-06-17 2004-02-05 Ralph Klinke Method of stabilizing proteins at low pH
DE10227232A1 (de) 2002-06-18 2004-01-15 Aventis Pharma Deutschland Gmbh Saure Insulinzubereitungen mit verbesserter Stabilität
EP1525219B1 (en) 2002-07-04 2009-05-27 Zealand Pharma A/S Glp-1 and methods for treating diabetes
DE10235168A1 (de) 2002-08-01 2004-02-12 Aventis Pharma Deutschland Gmbh Verfahren zur Reinigung von Preproinsulin
EP1558237A4 (en) 2002-09-27 2007-01-17 Martek Biosciences Corp IMPROVED GLYCEMIC REGULATION IN PREDIABETE AND / OR DIABETES TYPE II USING DOCOSAHEXAENOIC ACID
KR20050083713A (ko) 2002-10-02 2005-08-26 질랜드 파마 에이/에스 안정화된 엑센딘-4 화합물
DK1583541T3 (da) 2002-11-20 2011-04-11 Neuronova Ab Forbindelser og fremgangsmåder til at øge neurogenese
US6969702B2 (en) 2002-11-20 2005-11-29 Neuronova Ab Compounds and methods for increasing neurogenesis
US20050209142A1 (en) 2002-11-20 2005-09-22 Goran Bertilsson Compounds and methods for increasing neurogenesis
CN1413582A (zh) 2002-11-29 2003-04-30 贵州圣济堂制药有限公司 盐酸二甲双胍肠溶片及其制备方法
EP1569682A2 (en) 2002-12-03 2005-09-07 Novo Nordisk A/S Combination treatment using exendin-4 and thiazolidinediones
GB0309154D0 (en) 2003-01-14 2003-05-28 Aventis Pharma Inc Use of insulin glargine to reduce or prevent cardiovascular events in patients being treated for dysglycemia
GB0304822D0 (en) 2003-03-03 2003-04-09 Dca Internat Ltd Improvements in and relating to a pen-type injector
AU2004216909A1 (en) 2003-03-04 2004-09-16 The Technology Development Company Ltd. Delivery system for drug and cell therapy
MXPA05009565A (es) 2003-03-11 2005-12-02 Novo Nordisk As Preparaciones farmaceuticas que comprenden insulina estabilizada con acido.
US20040186046A1 (en) 2003-03-17 2004-09-23 Pfizer Inc Treatment of type 1 diabetes with PDE5 inhibitors
KR20050121748A (ko) 2003-04-29 2005-12-27 일라이 릴리 앤드 캄파니 연장된 시간 작용을 갖는 인슐린 유사체
KR101293507B1 (ko) 2003-06-03 2013-08-06 노보 노르디스크 에이/에스 안정화된 약학적 펩티드 조성물
DE10325567B4 (de) 2003-06-05 2008-03-13 Mavig Gmbh Strahlenschutzanordnung mit separierbarer Umhüllung
JP2007504167A (ja) 2003-08-29 2007-03-01 セントカー・インコーポレーテツド 抗組織因子抗体を用いる移植片の生存を向上する方法
JP5518282B2 (ja) 2003-09-01 2014-06-11 ノヴォ ノルディスク アー／エス 安定なペプチドの製剤
WO2005023291A2 (en) 2003-09-11 2005-03-17 Novo Nordisk A/S Use of glp1-agonists in the treatment of patients with type i diabetes
EP1667724A2 (en) 2003-09-19 2006-06-14 Novo Nordisk A/S Albumin-binding derivatives of therapeutic peptides
EP1684793B1 (en) 2003-11-13 2011-09-21 Novo Nordisk A/S Pharmaceutical composition comprising an insulinotropic glp-1(7-37) analogue, asp(b28)-insulin, and a surfactant
US20060287221A1 (en) 2003-11-13 2006-12-21 Novo Nordisk A/S Soluble pharmaceutical compositions for parenteral administration comprising a GLP-1 peptide and an insulin peptide of short time action for treatment of diabetes and bulimia
US20050201978A1 (en) 2003-11-17 2005-09-15 Lipton James S. Tumor and infectious disease therapeutic compositions
WO2005061222A1 (en) 2003-12-22 2005-07-07 Novo Nordisk A/S Transparent, flexible, impermeable plastic container for storage of pharmaceutical liquids
US20060210614A1 (en) 2003-12-26 2006-09-21 Nastech Pharmaceutical Company Inc. Method of treatment of a metabolic disease using intranasal administration of exendin peptide
EP1701714A2 (en) 2004-01-07 2006-09-20 Nektar Therapeutics Improved sustained release compositions for pulmonary administration of insulin
US20070027063A1 (en) 2004-01-12 2007-02-01 Mannkind Corporation Method of preserving the function of insulin-producing cells
US20080248999A1 (en) 2007-04-04 2008-10-09 Biodel Inc. Amylin formulations
US20080090753A1 (en) 2004-03-12 2008-04-17 Biodel, Inc. Rapid Acting Injectable Insulin Compositions
CA2563379A1 (en) 2004-03-31 2005-10-20 Centocor, Inc. Human glp-1 mimetibodies, compositions, methods and uses
CA2566873C (en) 2004-05-20 2013-02-12 Diamedica Inc. Use of drug combinations for treating insulin resistance
WO2005117948A1 (en) 2004-06-01 2005-12-15 Ares Trading S.A. Method of stabilizing proteins
EP1758580A4 (en) 2004-06-24 2008-01-16 Incyte Corp N-SUBSTITUTED PIPERIDINE AND ITS USE AS A MEDICAMENT
WO2006000567A2 (en) 2004-06-28 2006-01-05 Novo Nordisk A/S Use of glp-1 receptor agonists and / or dpp-iv inhibitors in combination with proton pump inhibitors and ppar agonists for the preparation of a medicament for the treatment of diabetes type i i and impaired pancreatic beta-cell function
JP2008507280A (ja) 2004-07-21 2008-03-13 アンブレツクス・インコーポレイテツド 非天然コードアミノ酸を用いた生合成ポリペプチド
CA2573856A1 (en) 2004-08-03 2006-02-16 Emisphere Technologies, Inc. Antidiabetic oral insulin-biguanide combination
DE602005008071D1 (de) 2004-08-13 2008-08-21 Hoffmann La Roche C-terminale modifikation von polypeptiden
DE102004043153B4 (de) 2004-09-03 2013-11-21 Philipps-Universität Marburg Erfindung betreffend GLP-1 und Exendin
WO2006028110A1 (ja) 2004-09-07 2006-03-16 Chugai Seiyaku Kabushiki Kaisha 水溶性ヒアルロン酸修飾物の製造方法
US20060073213A1 (en) 2004-09-15 2006-04-06 Hotamisligil Gokhan S Reducing ER stress in the treatment of obesity and diabetes
WO2006029634A2 (en) 2004-09-17 2006-03-23 Novo Nordisk A/S Pharmaceutical compositions containing insulin and insulinotropic peptide
JP2006137678A (ja) 2004-11-10 2006-06-01 Shionogi & Co Ltd インターロイキン−２組成物
JP5175103B2 (ja) 2004-11-12 2013-04-03 ノヴォ ノルディスク アー／エス 安定なペプチド製剤
WO2006051103A2 (en) 2004-11-12 2006-05-18 Novo Nordisk A/S Stable formulations of peptides
DE102004058306A1 (de) 2004-12-01 2006-07-27 Sanofi-Aventis Deutschland Gmbh Verfahren zur Herstellung von Carboxy-terminal amidierten Peptiden
SE0402976L (sv) 2004-12-03 2006-06-04 Mederio Ag Medicinsk produkt
SG158158A1 (en) 2004-12-22 2010-01-29 Centocor Inc Glp-1 agonists, compositions, methods and uses
US7879361B2 (en) 2005-01-04 2011-02-01 Gp Medical, Inc. Nanoparticles for drug delivery
US20090142338A1 (en) 2005-03-04 2009-06-04 Curedm, Inc. Methods and Compositions for Treating Type 1 and Type 2 Diabetes Mellitus and Related Conditions
ES2365410T3 (es) 2005-04-08 2011-10-04 Amylin Pharmaceuticals, Inc. Formulaciones farmacéuticas que comprenden péptido de incretina y un disolvente polar aprótico.
WO2006125763A1 (en) 2005-05-25 2006-11-30 Novo Nordisk A/S Stabilized polypeptide formulations
JP5198261B2 (ja) 2005-06-06 2013-05-15 カムルス エービー Ｇｌｐ−１類似体製剤
US7902254B1 (en) 2005-06-27 2011-03-08 Newtree Co., Ltd. Method for treating conditions mediated by PPAR using macelignan
US20080227847A1 (en) 2005-07-07 2008-09-18 Aditech Pharma Ab Novel Salts of Fumaric Acid Monoalkylesters and Their Pharmaceutical Use
WO2007024700A2 (en) 2005-08-19 2007-03-01 Amylin Pharmaceuticals, Inc. Exendin for treating diabetes and reducing body weight
JP2009507050A (ja) 2005-09-08 2009-02-19 ガストロテック・ファルマ・アクティーゼルスカブ 胆道ジスキネジーおよび／または胆道痛／不快の治療のためのｇｌｐ−１分子の使用
PT1926749E (pt) 2005-09-14 2011-09-29 Sanofi Aventis Deutschland Clivagem de precursores de insulinas por uma variante de tripsina
CN101267838B (zh) * 2005-09-20 2012-09-05 诺瓦提斯公司 Dpp-iv抑制剂降低低血糖事件的用途
KR101368525B1 (ko) 2005-09-20 2014-03-06 노파르티스 아게 저혈당 증상을 저하시키기 위한 ｄｐｐ-ⅳ 억제제의 용도
EP1945142B1 (en) 2005-09-26 2013-12-25 Medtronic, Inc. Prosthetic cardiac and venous valves
KR101105871B1 (ko) 2005-09-27 2012-01-16 주식회사 엘지생명과학 인 난포자극호르몬의 안정한 용액 제형
DE102005046113A1 (de) 2005-09-27 2007-03-29 Sanofi-Aventis Deutschland Gmbh Verfahren zur Amidierung von Polypetiden mit C-terminalen basischen Aminosäuren unter Verwendung spezifischer Endoproteasen
US8084420B2 (en) 2005-09-29 2011-12-27 Biodel Inc. Rapid acting and long acting insulin combination formulations
US20090264732A1 (en) 2005-10-11 2009-10-22 Huntington Medical Research Institutes Imaging agents and methods of use thereof
MY144556A (en) 2005-10-24 2011-09-30 Nestec Sa Dietary fiber formulation and method of administration
BRPI0520704A2 (pt) 2005-11-30 2009-05-19 Generex Pharm Inc formulação farmacêutica absorvida oralmente e método de administração
US20100029558A1 (en) 2005-12-06 2010-02-04 Bristow Cynthia L Alpha1 proteinase inhibitor peptides methods and use
WO2007075534A2 (en) 2005-12-16 2007-07-05 Nektar Therapeutics Al, Corporation Polymer conjugates of glp-1
US8435940B2 (en) 2006-01-05 2013-05-07 University Of Utah Research Foundation Methods and compositions related to improving properties of pharmacological agents targeting nervous system
WO2007081824A2 (en) 2006-01-06 2007-07-19 Case Western Reserve University Fibrillation resistant proteins
FR2896157B1 (fr) * 2006-01-13 2008-09-12 Merck Sante Soc Par Actions Si Combinaison de derives de triazine et d'agents de stimulation de secretion d'insuline.
WO2007082381A1 (en) 2006-01-20 2007-07-26 Diamedica Inc. Compositions containing (s)-bethanechol and their use in the treatment of insulin resistance, type 2 diabetes, glucose intolerance and related disorders
US20070191271A1 (en) 2006-02-10 2007-08-16 Dow Pharmaceutical Sciences Method for stabilizing polypeptides lacking methionine
WO2007095288A2 (en) 2006-02-13 2007-08-23 Nektar Therapeutics Methionine-containing protein or peptide compositions and methods of making and using
US7763582B2 (en) 2006-02-21 2010-07-27 University Of Medicine And Dentistry Of New Jersey Localized insulin delivery for bone healing
EP2241327A1 (en) 2006-03-15 2010-10-20 Novo Nordisk A/S Mixtures of Amylin and Insulin
TW200806317A (en) 2006-03-20 2008-02-01 Wyeth Corp Methods for reducing protein aggregation
EP2004213A1 (en) 2006-04-03 2008-12-24 Novo Nordisk A/S Glp-1 peptide agonists
CN101454019A (zh) 2006-04-12 2009-06-10 百达尔公司 速效和长效胰岛素联合制剂
MX2008013168A (es) 2006-04-13 2008-10-27 Sod Conseils Rech Applic Composiciones faramaceuticas del peptido 1 similar al glucagon humano, exendina-4 y análogos de los mismos.
CA2652989A1 (en) 2006-06-08 2007-12-13 Diabecore Medical Inc. Derivatized insulin oligomers
DE102006031962A1 (de) 2006-07-11 2008-01-17 Sanofi-Aventis Deutschland Gmbh Amidiertes Insulin Glargin
WO2008013938A2 (en) 2006-07-27 2008-01-31 Nektar Therapeutics Aerosolizable formulation comprising insulin for pulmonary delivery
JP5399244B2 (ja) 2006-08-17 2014-01-29 アミリン・ファーマシューティカルズ，リミテッド・ライアビリティ・カンパニー 選択可能な特性を持つｄｐｐ−ｉｖ耐性ｇｉｐハイブリッドポリペプチド
EP2057189B1 (en) 2006-08-25 2013-03-06 Novo Nordisk A/S Acylated exendin-4 compounds
UA100497C2 (ru) 2006-09-07 2013-01-10 Никомед Гмбх Комбинированное лечение сахарного диабета
EP2074141B1 (en) 2006-09-22 2016-08-10 Novo Nordisk A/S Protease resistant insulin analogues
MX2009011123A (es) 2007-04-23 2009-11-02 Intarcia Therapeutics Inc Formulaciones de suspensiones de peptidos insulinotropicos y sus usos.
WO2008145323A1 (en) 2007-05-31 2008-12-04 F. Hoffmann-La Roche Ag Pharmaceutical formulation for interferons
CN101678174A (zh) 2007-06-14 2010-03-24 塞诺菲-安万特德国有限公司 双室卡普耳
CN101678175A (zh) 2007-06-14 2010-03-24 塞诺菲-安万特德国有限公司 带有附件的双室卡普耳
EP2173407B1 (en) 2007-07-02 2020-02-19 Roche Diabetes Care GmbH A device for drug delivery
WO2009023566A2 (en) 2007-08-09 2009-02-19 Genzyme Corporation Method of treating autoimmune disease with mesenchymal stem cells
JP5710253B2 (ja) 2007-08-13 2015-04-30 ノボ・ノルデイスク・エー／エス 速効型インスリンアナログ
CN101366692A (zh) 2007-08-15 2009-02-18 江苏豪森药业股份有限公司 一种稳定的艾塞那肽制剂
GB0717399D0 (en) 2007-09-07 2007-10-17 Uutech Ltd Use of GLP-1 analogues for the treatment of disorders associated with dysfunctional synaptic transmission
GB0717388D0 (en) 2007-09-07 2007-10-17 Uutech Ltd Use of GIP for the treatment of disorders associated with dysfunctional synaptic transmission
KR20100057640A (ko) 2007-09-11 2010-05-31 몬도바이오테크 래보래토리즈 아게 치료제로서의 인슐린 ｃ-펩티드 단독 또는 ｇｌｐ-1과의 배합물의 용도
US20090104210A1 (en) 2007-10-17 2009-04-23 Tota Michael R Peptide compounds for treating obesity and insulin resistance
RS52566B (sr) 2007-11-01 2013-04-30 Merck Serono S.A. Tečne formulacije lh
CN101932601B (zh) 2007-11-08 2016-08-03 诺沃-诺迪斯克有限公司 胰岛素衍生物
CA2705821A1 (en) 2007-11-16 2009-05-22 Novo Nordisk A/S Pharmaceutical compositions containing insulin and an insulinotropic peptide
CN101444618B (zh) 2007-11-26 2012-06-13 杭州九源基因工程有限公司 含有艾塞那肽的药物制剂
CN102026666B (zh) 2007-12-11 2013-10-16 常山凯捷健生物药物研发（河北）有限公司 促胰岛素肽缀合物制剂
AU2009204309B2 (en) 2008-01-04 2012-11-22 Biodel, Inc. Insulin formulations for insulin release as a function of tissue glucose levels
NZ586590A (en) 2008-01-09 2012-06-29 Sanofi Aventis Deutschland Insulin analogues or derivatives having an extremely delayed time-action profile
JP5695909B2 (ja) 2008-01-09 2015-04-08 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 極度に遅延した時間作用プロファイルを有する新規なインスリン誘導体
DE102008003568A1 (de) 2008-01-09 2009-07-16 Sanofi-Aventis Deutschland Gmbh Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil
DE102008003566A1 (de) 2008-01-09 2009-07-16 Sanofi-Aventis Deutschland Gmbh Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil
ME01337B (me) 2008-02-08 2013-12-20 Biogenerix Ag Tečni preparat fsh
DK2240155T3 (da) 2008-02-13 2012-09-17 Intarcia Therapeutics Inc Indretninger, formuleringer og fremgangsmåder til levering af flere gavnlige midler
KR101556514B1 (ko) 2008-02-19 2015-10-02 바이오콘 리미티드 효모에서 발현된 정제된 이형 인슐린을 수득하는 방법
TWI394580B (zh) 2008-04-28 2013-05-01 Halozyme Inc 超快起作用胰島素組成物
US8329419B2 (en) 2008-05-23 2012-12-11 Amylin Pharmaceuticals, Llc GLP-1 receptor agonist bioassays
TWI451876B (zh) 2008-06-13 2014-09-11 Lilly Co Eli 聚乙二醇化之離脯胰島素化合物
EP4074327A1 (en) 2008-06-27 2022-10-19 Duke University Therapeutic agents comprising elastin-like peptides
CA2735289A1 (en) 2008-08-30 2010-03-04 Sanofi-Aventis Deutschland Gmbh Cartridge and needle system therefor
WO2010028055A1 (en) 2008-09-02 2010-03-11 Biodel, Inc. Insulin with a basal release profile
KR20110076918A (ko) 2008-09-10 2011-07-06 제넨테크, 인크. 단백질의 산화성 분해를 방지하기 위한 조성물 및 방법
CN101670096B (zh) 2008-09-11 2013-01-16 杭州九源基因工程有限公司 含有艾塞那肽的药物制剂
US20100092566A1 (en) 2008-10-15 2010-04-15 Alessi Thomas R Highly concentrated drug particles, formulations, suspensions and uses thereof
DK3228320T3 (da) 2008-10-17 2020-03-09 Sanofi Aventis Deutschland Kombination af et insulin og en glp-1-agonist
DE102008053048A1 (de) 2008-10-24 2010-04-29 Sanofi-Aventis Deutschland Gmbh Kombination von einem Insulin und einem GLP-1-Agonisten
AU2009309623B9 (en) 2008-10-30 2014-10-02 Novo Nordisk A/S Treating diabetes melitus using insulin injections with less than daily injection frequency
JP2009091363A (ja) 2008-11-21 2009-04-30 Asahi Kasei Pharma Kk Ｐｔｈの安定化水溶液注射剤
MA32970B1 (fr) * 2008-12-15 2012-01-02 Zealand Pharma As Analogues du glucagon
AR075204A1 (es) 2009-01-29 2011-03-16 Boehringer Ingelheim Int Inhibidores de dpp-4 y composiciones farmaceuticas que los comprenden, utiles para tratar enfermedades metabolicas en pacientes pediatricos, particularmente diabetes mellitus tipo 2
JP5677321B2 (ja) 2009-02-04 2015-02-25 サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング 血糖コントロール用の情報を提供するための医療デバイス及び方法
NZ594044A (en) 2009-02-13 2014-08-29 Boehringer Ingelheim Int Antidiabetic medications comprising a dpp-4 inhibitor (linagliptin) optionally in combination with other antidiabetics
EP2435061A4 (en) 2009-05-28 2013-03-27 Amylin Pharmaceuticals Inc DAMPING GLP-1 RECEPTOR AGONIST COMPOUNDS
TW201105346A (en) 2009-07-06 2011-02-16 Sanofi Aventis Deutschland Heat-stable and vibration-stable insulin preparations
US20120232002A1 (en) 2009-07-06 2012-09-13 Sanofi-Aventis Deutschland Gmbh Slow-acting insulin preparations
MX2012000304A (es) 2009-07-06 2012-01-27 Sanofi Aventis Deutschland Preparaciones insulinicas que comprenden metionina.
US8709400B2 (en) 2009-07-27 2014-04-29 Washington University Inducement of organogenetic tolerance for pancreatic xenotransplant
KR101759499B1 (ko) 2009-07-31 2017-07-19 사노피-아벤티스 도이칠란트 게엠베하 지속형 인슐린 조성물
US8642548B2 (en) 2009-08-07 2014-02-04 Mannkind Corporation Val (8) GLP-1 composition and method for treating functional dyspepsia and/or irritable bowel syndrome
AR078161A1 (es) 2009-09-11 2011-10-19 Hoffmann La Roche Formulaciones farmaceuticas muy concentradas de un anticuerpo anti cd20. uso de la formulacion. metodo de tratamiento.
CA2685638C (en) 2009-11-13 2017-02-28 Sanofi-Aventis Deutschland Gmbh Method of treatment of diabetes type 2 comprising add-on therapy to insulin glargine and metformin
CN102711804B (zh) 2009-11-13 2015-09-16 赛诺菲-安万特德国有限公司 包含glp-1激动剂和甲硫氨酸的药物组合物
ME01546B (me) 2009-11-13 2014-04-20 Sanofi Aventis Deutschland Liksisenatid kao dodatna terapija insulin glarginu i metforminu za liječenje dijabetesa tipa 2
PL3417871T3 (pl) 2009-11-13 2021-06-14 Sanofi-Aventis Deutschland Gmbh Kompozycja farmaceutyczna zawierająca agonistę GLP-1, insulinę i metioninę
PL2324853T3 (pl) 2009-11-13 2016-01-29 Sanofi Aventis Deutschland Liksysenatyd jako dodatek do metforminy w leczeniu cukrzycy typu 2
US20110118180A1 (en) 2009-11-13 2011-05-19 Sanofi-Aventis Deutschland Gmbh Method of treatment of diabetes type 2 comprising add-on therapy to metformin
US20110118178A1 (en) * 2009-11-13 2011-05-19 Sanofi-Aventis Deutschland Gmbh Method of treatment of diabetes type 2 comprising add-on therapy to insulin glargine and metformin
WO2011075623A1 (en) 2009-12-18 2011-06-23 Latitude Pharmaceuticals, Inc. One - phase gel compos ition compri s ing phos pholi pids
EP2460527A1 (en) 2010-01-21 2012-06-06 Sanofi Pharmaceutical composition for treating a metabolic syndrome
BR112012020481A2 (pt) 2010-02-22 2017-01-10 Univ Case Western Reserve método para tratar um paciente, o método compreendendo administrar uma formulação farmacêutica contendo uma quantidade fisiologicamente efetiva de um análogo de insulina ou um sal fisiologicamente.
AR081066A1 (es) 2010-04-02 2012-06-06 Hanmi Holdings Co Ltd Conjugado de insulina donde se usa un fragmento de inmunoglobulina
AR080884A1 (es) 2010-04-14 2012-05-16 Sanofi Aventis Conjugados de insulina-sirna
US8637458B2 (en) 2010-05-12 2014-01-28 Biodel Inc. Insulin with a stable basal release profile
AU2011202239C1 (en) 2010-05-19 2017-03-16 Sanofi Long-acting formulations of insulins
WO2011144674A2 (en) 2010-05-20 2011-11-24 Sanofi-Aventis Deutschland Gmbh PHARMACEUTICAL FORMULATION COMPRISING INSULIN GLARGINE AND SBE4-ß-CYD
EP2389945A1 (en) 2010-05-28 2011-11-30 Sanofi-Aventis Deutschland GmbH Pharmaceutical composition comprising AVE0010 and insulin glargine
WO2011160066A1 (en) 2010-06-17 2011-12-22 Regents Of The University Of Minnesota Production of insulin producing cells
US8532933B2 (en) 2010-06-18 2013-09-10 Roche Diagnostics Operations, Inc. Insulin optimization systems and testing methods with adjusted exit criterion accounting for system noise associated with biomarkers
US20130137645A1 (en) 2010-07-19 2013-05-30 Mary S. Rosendahl Modified peptides and proteins
RU2546520C2 (ru) 2010-08-30 2015-04-10 Санофи-Авентис Дойчланд Гмбх Применение ave0010 для производства лекарственного средства для лечения сахарного диабета 2 типа
EP2438930A1 (en) 2010-09-17 2012-04-11 Sanofi-Aventis Deutschland GmbH Prodrugs comprising an exendin linker conjugate
EP2632478B1 (en) 2010-10-27 2019-07-24 Novo Nordisk A/S Treating diabetes melitus using insulin injections administered with varying injection intervals
WO2012065996A1 (en) 2010-11-15 2012-05-24 Sanofi-Aventis Deutschland Gmbh PHARMACEUTICAL FORMULATION COMPRISING INSULIN GLARGINE AND MALTOSYL-ß-CYCLODEXTRIN
WO2012066086A1 (en) 2010-11-17 2012-05-24 Sanofi-Aventis Deutschland Gmbh PHARMACEUTICAL FORMULATION COMPRISING INSULIN GLARGINE AND SULFOBUTYL ETHER 7-ß-CYCLODEXTRIN
EP2651432A1 (en) 2010-12-14 2013-10-23 Novo Nordisk A/S Fast-acting insulin in combination with long-acting insulin
EP2670427A1 (en) 2011-02-02 2013-12-11 Sanofi-Aventis Deutschland GmbH Prevention of hypoglycaemia in diabetes mellitus type 2 patients
PL2683406T3 (pl) 2011-03-11 2019-11-29 Beth Israel Deaconess Medical Ct Inc Przeciwciała anty-cd40 i ich zastosowania
US20120277147A1 (en) 2011-03-29 2012-11-01 Sanofi-Aventis Deutschland Gmbh Prevention of hypoglycaemia in diabetes mellitus type 2 patients
US8735349B2 (en) 2011-05-13 2014-05-27 Sanofi-Aventis Deutschland Gmbh Method for improving glucose tolerance in a diabetes type 2 patient of younger than 50 years and having postprandial plasma glucose concentration of at least 14 mmol/L
US20130040878A1 (en) 2011-05-13 2013-02-14 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for use in the treatment of diabetes type 2 patients
AU2012257849B2 (en) 2011-05-13 2017-03-30 Sanofi-Aventis Deutschland Gmbh Lixisenatide and metformin for treatment of diabetes type 2
US9821032B2 (en) * 2011-05-13 2017-11-21 Sanofi-Aventis Deutschland Gmbh Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
JP2014520159A (ja) 2011-06-24 2014-08-21 アミリン・ファーマシューティカルズ，リミテッド・ライアビリティ・カンパニー Ｇｌｐ−１受容体アゴニストの徐放性製剤による糖尿病の治療方法
BR112014004726A2 (pt) 2011-08-29 2017-04-04 Sanofi Aventis Deutschland combinação farmacêutica para uso no controle glicêmico em pacientes de diabetes tipo 2
TWI559929B (en) 2011-09-01 2016-12-01 Sanofi Aventis Deutschland Pharmaceutical composition for use in the treatment of a neurodegenerative disease
ES2562651T3 (es) 2011-10-04 2016-03-07 Sanofi-Aventis Deutschland Gmbh Lixisenatida para el uso en el tratamiento de la estenosis o/y la obstrucción del sistema de conductos pancreáticos
WO2013050378A1 (en) 2011-10-04 2013-04-11 Sanofi-Aventis Deutschland Gmbh Glp-1 agonist for use in the treatment of stenosis or/and obstruction in the biliary tract
IN2014CN02616A (enExample) * 2011-10-28 2015-06-26 Sanofi Aventis Deutschland
US20130172244A1 (en) * 2011-12-29 2013-07-04 Thomas Klein Subcutaneous therapeutic use of dpp-4 inhibitor
US8901484B2 (en) 2012-04-27 2014-12-02 Sanofi-Aventis Deutschland Gmbh Quantification of impurities for release testing of peptide products
US9522235B2 (en) 2012-05-22 2016-12-20 Kaleo, Inc. Devices and methods for delivering medicaments from a multi-chamber container
AR092862A1 (es) 2012-07-25 2015-05-06 Hanmi Pharm Ind Co Ltd Formulacion liquida de insulina de accion prolongada y un peptido insulinotropico y metodo de preparacion
TWI641381B (zh) 2013-02-04 2018-11-21 法商賽諾菲公司 胰島素類似物及／或胰島素衍生物之穩定化醫藥調配物
MX364911B (es) 2013-03-01 2019-05-13 Fundacio Hospital Univ Vall Dhebron Institut De Recerca Peptidos para su uso en el tratamiento topico de enfermedades neurodegenerativas retinianas, en particular en fases de tempranas de retinopatia diabetica y otras enfermedades retinianas en las cuales la neurodegeneracion desempeña una funcion esencial.
GB201303771D0 (en) 2013-03-04 2013-04-17 Midatech Ltd Nanoparticles peptide compositions
RU2705797C2 (ru) 2013-04-03 2019-11-12 Санофи Лечение сахарного диабета с помощью составов инсулинов длительного действия
US20140371141A1 (en) * 2013-06-17 2014-12-18 Sanofi-Aventis Deutschland Gmbh Insulin glargine/lixisenatide fixed ratio formulation
AR098168A1 (es) 2013-10-25 2016-05-04 Sanofi Sa Formulación estable de insulina glulisina
ES2949095T3 (es) 2014-12-12 2023-09-25 Sanofi Aventis Deutschland Formulación de relación fija de insulina glargina/lixisenatida
AR103415A1 (es) 2015-01-16 2017-05-10 Sanofi Aventis Deutschland Tratamiento de pacientes pediátricos con diabetes mellitus de tipo 2
TWI748945B (zh) 2015-03-13 2021-12-11 德商賽諾菲阿凡提斯德意志有限公司 第２型糖尿病病患治療
TW201705975A (zh) 2015-03-18 2017-02-16 賽諾菲阿凡提斯德意志有限公司 第２型糖尿病病患之治療

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10117909B2 (en) 2008-10-17 2018-11-06 Sanofi-Aventis Deutschland Gmbh Combination of an insulin and a GLP-1 agonist
US12303598B2 (en) 2009-11-13 2025-05-20 Sanofi-Aventis Deutschland Gmbh Pharmaceutical composition comprising a GLP-1-agonist and methionine
US12186374B2 (en) 2014-12-12 2025-01-07 Sanofi-Aventis Deutschland Gmbh Insulin glargine/lixisenatide fixed ratio formulation
US10434147B2 (en) 2015-03-13 2019-10-08 Sanofi-Aventis Deutschland Gmbh Treatment type 2 diabetes mellitus patients
US10159713B2 (en) 2015-03-18 2018-12-25 Sanofi-Aventis Deutschland Gmbh Treatment of type 2 diabetes mellitus patients

Also Published As

Publication number Publication date
JP2018509419A (ja) 2018-04-05
EA201792030A1 (ru) 2018-01-31
NZ736299A (en) 2023-02-24
CA2979448A1 (en) 2016-09-22
TWI748945B (zh) 2021-12-11
HK1244216A1 (zh) 2018-08-03
TW201705974A (zh) 2017-02-16
KR102694473B1 (ko) 2024-08-13
SG11201707372YA (en) 2017-10-30
US20180092965A1 (en) 2018-04-05
AU2016232448C1 (en) 2021-09-16
TN2017000373A1 (en) 2019-01-16
ES2922551T3 (es) 2022-09-16
EP3268029B1 (en) 2022-04-27
MX2017011723A (es) 2017-11-13
EP3268029A1 (en) 2018-01-17
CL2017002293A1 (es) 2018-05-04
PL3268029T3 (pl) 2022-08-16
US10434147B2 (en) 2019-10-08
AU2016232448A1 (en) 2017-11-02
MA42287B1 (fr) 2022-08-31
AU2016232448B2 (en) 2021-05-27
BR112017018388A2 (pt) 2018-04-17
KR20170123699A (ko) 2017-11-08
CN107921099A (zh) 2018-04-17
IL254496B (en) 2022-02-01
MA42287A (fr) 2021-06-02
JP6857129B2 (ja) 2021-04-14
EA034940B1 (ru) 2020-04-09
AR103914A1 (es) 2017-06-14
PH12017501662A1 (en) 2018-03-19
MX389091B (es) 2025-03-20
PT3268029T (pt) 2022-07-18
IL254496A0 (en) 2017-11-30
WO2016146514A1 (en) 2016-09-22

Similar Documents

Publication Publication Date Title
US10434147B2 (en) Treatment type 2 diabetes mellitus patients
US20220054594A1 (en) Use of ave0010 for the manufacture of a medicament for the treatment of diabetes mellitus type 2
JP6329487B2 (ja) ２型糖尿病の治療プロトコル
US20240173384A1 (en) Treatment of pediatric type 2 diabetes mellitus patients
JP6676108B2 (ja) ２型糖尿病の処置のためのリキシセナチド及びメトホルミン
JP6410600B2 (ja) ２型糖尿病患者における低血糖症の予防
US20110118180A1 (en) Method of treatment of diabetes type 2 comprising add-on therapy to metformin
DK3010530T3 (en) FIXED-FORMULATED FORMULATION BETWEEN INSULIN GLARGIN AND LIXISENATIDE
CN107375909A (zh) 在2型糖尿病患者中预防低血糖症
KR20140038410A (ko) 2형 당뇨병에서 기저 인슐린에 대한 부가 치료요법으로서의 릭시세나티드
HUE027989T2 (en) A pharmaceutical composition for use in glycemic control in patients with type 2 diabetes
US20250319163A1 (en) Treatment of type 2 diabetes mellitus
KR20110052990A (ko) 인슐린 글라르긴 및 메트포르민에 대한 부가적 요법을 포함하는 2형 당뇨병의 치료 방법
HK1244216B (en) Treatment of type 2 diabetes mellitus patients
BR112017018388B1 (pt) Uso de combinação farmacêutica para o controle da glicemia em indivíduo com diabetes mellitus tipo 2
KR20110052987A (ko) 메트포르민에 대한 부가적 요법을 포함하는 2형 당뇨병의 치료 방법

Legal Events

Date Code Title Description
AS Assignment

Owner name: SANOFI-AVENTIS DEUTSCHLAND GMBH, GERMANY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ROY, CHRISTINE;SOUHAMI, ELISABETH;DEMIL, NACIMA;AND OTHERS;SIGNING DATES FROM 20160415 TO 20160608;REEL/FRAME:039120/0893

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION