CN115192625A - Oral composition - Google Patents

Oral composition Download PDF

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CN115192625A
CN115192625A CN202210763080.0A CN202210763080A CN115192625A CN 115192625 A CN115192625 A CN 115192625A CN 202210763080 A CN202210763080 A CN 202210763080A CN 115192625 A CN115192625 A CN 115192625A
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active ingredient
soybean oil
insulin
weight ratio
diabetes
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彭文
王峨县
孙磊
黄星
刘续征
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Hefei Tianhui Hatching Technology Co ltd
Shandong Haibang Biotechnology Co ltd
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Hefei Tianhui Hatching Technology Co ltd
Shandong Haibang Biotechnology Co ltd
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Priority to CN202210763080.0A priority Critical patent/CN115192625A/en
Priority to CN202310753650.2A priority patent/CN116999398A/en
Publication of CN115192625A publication Critical patent/CN115192625A/en
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    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
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    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
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    • A—HUMAN NECESSITIES
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    • 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
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Abstract

Aiming at the existing problems, the invention provides an oral composition which comprises an active ingredient and soybean oil, wherein the active ingredient comprises metformin and/or eicosapentaenoic acid salt of phenformin, and the active ingredient and the soybean oil synergistically lower the sugar, so that the sugar-reducing effect of the active ingredient can be obviously improved.

Description

Oral composition
Technical Field
The invention belongs to the field of diabetes treatment, and particularly relates to an oral composition.
Background
Diabetes is a chronic metabolic disease, seriously threatening global health.
Biguanides are important drugs for the treatment of diabetes, and common biguanides include metformin and phenformin, which act by reducing hepatic glycogen production, inhibiting glucose absorption in the intestinal tract, and increasing peripheral inhibition of glucose absorption and utilization, and increase insulin sensitivity by increasing peripheral sugar intake and utilization.
Metformin is the primary drug in the first-line and drug combination for controlling hyperglycemia in T2DM patients, and is recommended by diabetes treatment guidelines in several countries around the world. The 2020 version of Chinese guidelines for the prevention and treatment of type II diabetes indicate that metformin is currently the most commonly used hypoglycemic agent, has potential benefits (such as treatment of cardiovascular diseases, diabetic cardiovascular complications, etc.) in addition to a variety of hypoglycemic effects, and does not increase the risk of hypoglycemia. If there are no contraindications, metformin should remain in the therapeutic regimen for diabetes.
Metformin can be used for type 2 diabetes mellitus with ineffective blood sugar control by simple diet control and physical exercise, and can also be used for combined treatment with sulfonylureas drugs or insulin. Metformin has the formula:
Figure BDA0003724692110000011
it would therefore be a constant pursuit by those skilled in the art if the therapeutic efficacy of the eicosapentaenoic acid salt of metformin could be improved.
Disclosure of Invention
1. Problems to be solved
Aiming at the existing problems, the invention provides an oral composition which comprises an active ingredient and soybean oil, wherein the active ingredient comprises metformin and/or eicosapentaenoic acid salt of phenformin, and the active ingredient and the soybean oil synergistically lower the sugar, so that the sugar-reducing effect of the active ingredient can be obviously improved.
2. Technical scheme
In order to solve the above problems, the present invention adopts the following technical solutions.
In a first aspect, the present invention provides an oral composition comprising an active ingredient comprising metformin and/or an eicosapentaenoate of phenformin and soybean oil.
Preferably, the weight ratio of the active ingredients to the soybean oil is 100: (50 to 1000), preferably 100: (50 to 400), preferably 100: (400-1000).
Preferably, the weight ratio of the active ingredient to the soybean oil is
Active ingredient 100mg
Soybean oil 50mg
Or
Active ingredient 100mg
Soybean oil 400mg
Or
Active ingredient 100mg
1000mg of soybean oil.
In a second aspect, the present invention provides a pharmaceutical formulation comprising any one of the oral compositions described above and a pharmaceutical excipient.
Preferably, the pharmaceutical adjuvant comprises a binder, a disintegrant or a lubricant, and preferably, the pharmaceutical adjuvant further comprises a diluent, an emulsifier, a solubilizer, a colorant, an aromatic or a sweetener.
Preferably, the weight ratio of the binder, the lubricant and the disintegrant is:
0 to 4 of adhesive
0 to 20 portions of lubricant
0 to 6 portions of disintegrating agent
Or
0 to 3 parts of adhesive
0 to 10 parts of lubricant
0 to 3 portions of disintegrating agent
Or
Adhesive 3-4
10 to 20 portions of lubricant
3 to 6 portions of disintegrating agent.
Preferably, the adhesive is selected from one or more of starch slurry, gelatin solution, sucrose solution, polyvinylpyrrolidone, methylcellulose, ethyl cellulose, hydroxypropyl cellulose or hydroxypropyl methylcellulose, preferably, the disintegrating agent is selected from one or more of sodium carboxymethyl starch, dry starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose or cross-linked polyvinylpyrrolidone, preferably, the lubricant is selected from one or more of talcum powder, superfine silica gel powder, magnesium lauryl sulfate, polyethylene glycol, magnesium lauryl sulfate, stearic acid, calcium stearate or magnesium stearate.
Preferably, the dosage form of the pharmaceutical preparation is tablets, capsules, powder, granules, capsules, pills, suppositories, ointments, gels, aerosols, films, syrups, emulsions, suspensions or injections.
In a third aspect, the invention provides an oral composition as described in any one of the above and an application of a pharmaceutical preparation as described in any one of the above in preparing a medicament for treating or preventing hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, diabetes accompanied by non-alcoholic fatty liver, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver disease.
3. Advantageous effects
Compared with the prior art, the invention has the beneficial effects that:
(1) The oral composition can obviously improve the blood sugar reducing effect of the eicosapentaenoic acid salt of the metformin and/or the phenformin.
Detailed Description
In a first aspect, the present invention provides an oral composition comprising an active ingredient comprising metformin and/or an eicosapentaenoate of phenformin and soybean oil.
In one embodiment, the weight ratio of active ingredient to soybean oil is 100:50.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:55.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:60.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:65.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:70.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:75.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:80.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:85.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:90.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:95.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:100.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:110.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:120.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:130.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:150.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:170.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:190.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:200.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:220.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:230.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:240.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:250.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:270.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:300.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:310.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:320.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:350.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:370.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:390.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:400.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:430.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:450.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:470.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:480.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:500.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:520.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:550.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:600.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:650.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:700.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:750.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:800.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:850.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:900.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:950.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:1000.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:2000.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:3000.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:4000.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:5000.
in one embodiment, the weight ratio of active ingredient to soybean oil is 100:6000.
in one embodiment, the active ingredient weight is 5 mg/dose.
In one embodiment, the active ingredient is present in an amount of 10mg per dose.
In one embodiment, the active ingredient weight is 20 mg/dose.
In one embodiment, the active ingredient is 30 mg/dose.
In one embodiment, the active ingredient is 40 mg/dose.
In one embodiment, the active ingredient is present in an amount of 50mg per dose.
In one embodiment, the active ingredient is 70 mg/dose.
In one embodiment, the active ingredient is 100 mg/dose.
In one embodiment, the active ingredient is 130 mg/dose.
In one embodiment, the active ingredient is 200 mg/dose.
In one embodiment, the active ingredient weight is 250 mg/dose.
In one embodiment, the active ingredient is 300 mg/dose.
In one embodiment, the active ingredient has a weight of 400mg per dose.
In one embodiment, the active ingredient has a weight of 500mg per dose.
In one embodiment, the active ingredient is 600 mg/dose.
In one embodiment, the active ingredient is 700 mg/dose.
In one embodiment, the active ingredient has a weight of 800 mg/dose.
In one embodiment, the active ingredient weight is 900 mg/dose.
In one embodiment, the active ingredient weight is 1000 mg/dose.
In one embodiment, the active ingredient weight is 1100mg per dose.
In one embodiment, the active ingredient weight is 1200 mg/dose.
In one embodiment, the active ingredient weight is 1300 mg/dose.
In one embodiment, the active ingredient has a weight of 1400 mg/dose.
In one embodiment, the active ingredient has a weight of 1500mg per dose.
In one embodiment, the active ingredient has a weight of 1600mg per dose.
In one embodiment, the active ingredient is 1700 mg/dose.
In one embodiment, the active ingredient is 1800 mg/dose.
In one embodiment, the active ingredient has a weight of 2000mg per dose.
In one embodiment, the weight ratio of the active ingredient to the soybean oil is
Active ingredient 100mg
Soybean oil 50mg
Or
Active ingredient 100mg
Soybean oil 400mg
Or
Active ingredient 100mg
1000mg of soybean oil.
In a second aspect, the present invention provides a pharmaceutical formulation comprising any one of the oral compositions described above and a pharmaceutical excipient.
In one embodiment, the pharmaceutical excipient comprises a binder, a disintegrant, or a lubricant, and preferably, the pharmaceutical excipient further comprises a diluent, an emulsifier, a solubilizer, a colorant, a fragrance, or a sweetener.
In one embodiment, the weight ratio of the binder, lubricant and disintegrant is:
0 to 4 parts of adhesive
0 to 20 portions of lubricant
0 to 6 portions of disintegrating agent
Or
0 to 3 parts of adhesive
0 to 10 parts of lubricant
0 to 3 portions of disintegrating agent
Or
Adhesive 3-4
10 to 20 portions of lubricant
3 to 6 portions of disintegrating agent.
In one embodiment, the binder is selected from one or more of starch slurry, gelatin solution, sucrose solution, polyvinylpyrrolidone, methylcellulose, ethyl cellulose, hydroxypropyl cellulose or hydroxypropyl methylcellulose, preferably, the disintegrant is selected from one or more of sodium carboxymethyl starch, dry starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose or cross-linked polyvinylpyrrolidone, preferably, the lubricant is selected from one or more of talcum powder, silica gel micropowder, magnesium lauryl sulfate, polyethylene glycol, magnesium lauryl sulfate, stearic acid, calcium stearate or magnesium stearate.
In one embodiment, the pharmaceutical preparation is in the form of tablets, capsules, powders, granules, capsules, pills, suppositories, ointments, gels, aerosols, films, syrups, emulsions, suspensions or injections.
In a third aspect, the invention provides an oral composition as described in any one of the above and an application of a pharmaceutical preparation as described in any one of the above in preparing a medicament for treating or preventing hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, diabetes accompanied by non-alcoholic fatty liver, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver disease.
Example 1
Preparation of metformin eicosapentaenoate
The structure of eicosapentaenoic acid is as follows
Figure BDA0003724692110000091
Dissolving commercially available metformin hydrochloride with 1mo/L sodium hydroxide aqueous solution, stirring for half an hour, adding ethanol, performing rotary evaporation to remove the solvent, adding ethanol, filtering to remove sodium chloride, and performing rotary evaporation to the filtrate to obtain metformin free base.
Weighing 1mol of metformin free alkali, adding a proper amount of acetonitrile for dissolving, filtering to remove sodium chloride, slowly dropwise adding 0.9mol of eicosapentaenoic acid solution (dissolved in the acetonitrile) into the filtrate, stirring, cooling to 0-5 ℃, and filtering under the protection of nitrogen and in a dark place to obtain light tan solid, namely metformin eicosapentaenoic acid salt.
Example 2
Preparation of pharmaceutical compositions
Prescription (1000 tablets)
Raw and auxiliary materials Prescription amount (g)
Metformin eicosapentaenoate 100
Soybean oil 50
Polyvinylpyrrolidone 3
Magnesium lauryl sulfate 10
Sodium carboxymethyl starch 6
Weighing the raw materials according to the formula amount, sieving 100g of metformin eicosapentaenoic acid salt with a 80-mesh sieve, adding 6g of sodium carboxymethyl starch for mixing, adding 50g of soybean oil and a polyvinylpyrrolidone aqueous solution with the mass fraction of 3% (prepared by 3g of polyvinylpyrrolidone and purified water), uniformly stirring, sieving, granulating, after the granulation is finished, putting into a hot air circulation oven, drying at 50 ℃ for 0.5h, sieving with a 14-mesh sieve for size stabilization, after the size stabilization is finished, adding into a three-dimensional mixer, adding 10g of magnesium dodecyl sulfate, rotating at 50 r/min, mixing for 1h, after the mixing is finished, and tabletting to obtain the metformin eicosapentaenoic acid salt soybean composition oil.
Example 3
Preparation of pharmaceutical compositions
Prescription (1000 capsules)
Figure BDA0003724692110000101
Figure BDA0003724692110000111
Weighing the raw materials and auxiliary materials according to the formula, sieving 100g of metformin eicosapentaenoic acid salt by a sieve of 80 meshes, adding 400g of soybean oil, uniformly stirring, and filling into capsules after mixing to obtain the metformin eicosapentaenoic acid salt soybean oil composition.
Example 4
Preparation of pharmaceutical compositions
Prescription (1000 tablets)
Raw and auxiliary materials Prescription amount (g)
Metformin eicosapentaenoate 100
Soybean oil 1000
Polyvinylpyrrolidone 4
Magnesium stearate 20
Sodium carboxymethyl starch 3
Weighing the raw materials according to the formula, sieving 100g of metformin eicosapentaenoic acid salt with a 80-mesh sieve, adding 3g of sodium carboxymethyl starch for mixing, adding 1000g of soybean oil and a polyvinylpyrrolidone aqueous solution (prepared by 4g of polyvinylpyrrolidone and purified water) with the mass fraction of 5%, uniformly stirring, sieving, granulating, after the granulation is finished, putting the mixture into a hot air circulation oven, drying at 60 ℃ for 1h, sieving with a 14-mesh sieve for finishing granules, adding 20g of magnesium stearate into a three-dimensional mixer, adding 50 r/min for mixing for 1h, after the granulation is finished, tabletting to obtain the metformin eicosapentaenoic acid salt soybean oil composition.
Example 5
Animal experiments
The experimental method comprises the following steps:
establishing a diabetes model mouse:
70 rats are fasted for 6h, each rat is intraperitoneally injected with streptozotocin according to the dose of 40mg/kg once a day, and is simultaneously fed with high-fat feed, fasting blood sugar is measured by a Roche glucometer, and the fasting blood sugar value is more than 11.1mmol/L, which is considered as the success of molding. The model mice were randomly divided into 6 groups of 10 mice each. Another 10 unmolded rats were used as normal control groups.
Grouping experiments:
normal control group: 10 normal rats without molding were injected with physiological saline subcutaneously;
model control group: 10 model mice were injected subcutaneously with physiological saline;
drug group:
the pharmaceutical compositions prepared in examples 1-4 were administered, before each group was administered the gastric lavage drug, fasting blood glucose was measured with a glucometer, after each group was administered the gastric lavage drug, water was freely drunk and high-fat diet was continuously fed, after the 10 th administration, blood was sampled by cutting the tail, and blood glucose was measured with a glucometer for each rat to obtain the average blood glucose value of 10 rats in the corresponding group, the specific administration schedule was as follows:
group A: the pharmaceutical composition prepared in example 2 was administered once a day for 10 consecutive days after gavage of 10 model mice with a weight of 20mg/kg rat;
group B: the pharmaceutical composition prepared in example 3 was administered once a day for 10 consecutive days after gavage of 10 model mice with a weight of 20mg/kg rat;
group C: the pharmaceutical composition prepared in example 4 was administered once a day for 10 consecutive days after gavage of 10 model mice with a weight of 20mg/kg rat;
group D: 10 rats, metformin eicosapentaenoic acid salt prepared in example 1 was gavaged with 20mg/kg of body weight of the rats, and administered once a day for 10 days;
group E: 10 rats were gavaged with commercially available soybean oil at a rate of 20mg/kg, once daily for 10 days.
The results of the experiments are shown in the table below
Figure BDA0003724692110000121
Time/group classification Group A Group B Group C
0d 18.3±3.1 17.2±3.2 17.0±3.7
10d 7.1±1.5 6.7±3.4 7.5±2.3
Time/group classification Group D Group E Normal control group Model control group
0d 18.6±2.0 17.5±2.6 5.2±2.2 18.3±3.1
10d 10.3±1.9 18.3±2.0 6.0±2.4 19.0±2.5
Wherein, compared with the model control group, the P of the normal control group is less than 0.01, which indicates that the diabetes molding is successful.
Compared with a model control group, the group E has no obvious difference, and shows that the effect of reducing the blood sugar by using the soybean oil alone is not good.
Compared with the model control group, P of the A group, the B group, the C group and the D group is less than 0.01.
P is less than 0.05 in groups A, B and C compared with group D.
Therefore, the metformin eicosapentaenoic acid salt and the soybean oil are used together, so that the remarkable blood sugar reducing effect can be obtained, and the synergistic effect is achieved.

Claims (10)

1. Oral composition, characterized in that it comprises an active ingredient comprising metformin and/or the eicosapentaenoic acid salt of phenformin and soybean oil.
2. The oral composition according to claim 1, wherein the weight ratio of the active ingredient to soybean oil is 100: (50 to 1000), preferably 100: (50 to 400), preferably 100: (400-1000).
3. The oral composition of claim 1, wherein the weight ratio of the active ingredient to the soybean oil is
Active ingredient 100mg
Soybean oil 50mg
Or
Active ingredient 100mg
Soybean oil 400mg
Or
Active ingredient 100mg
1000mg of soybean oil.
4. Pharmaceutical preparation, characterized in that it comprises an oral composition according to any one of claims 1 to 3 and a pharmaceutical excipient.
5. The pharmaceutical formulation according to claim 4, wherein the pharmaceutical excipient comprises a binder, a disintegrant or a lubricant, preferably the pharmaceutical excipient further comprises a diluent, an emulsifier, a solubilizer, a colorant, a fragrance or a sweetener.
6. The pharmaceutical preparation according to claim 5, wherein the binder is selected from one or more of starch slurry, gelatin solution, sucrose solution, polyvinylpyrrolidone, methylcellulose, ethylcellulose, hydroxypropyl cellulose or hydroxypropyl methylcellulose, preferably, the disintegrant is selected from one or more of sodium carboxymethyl starch, dry starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose or cross-linked polyvinylpyrrolidone, preferably, the lubricant is selected from one or more of talc, aerosil, magnesium lauryl sulfate, polyethylene glycol, magnesium lauryl sulfate, stearic acid, calcium stearate or magnesium stearate.
7. The pharmaceutical preparation according to any one of claims 4 to 6, wherein the pharmaceutical preparation is in the form of tablets, capsules, powders, granules, capsules, pills, suppositories, ointments, gels, aerosols, films, syrups, emulsions, suspensions or injections.
8. A pharmaceutical formulation according to any one of claims 4 to 7, wherein the pharmaceutical formulation further comprises a second active ingredient which is a glucose-lowering drug, preferably wherein the second active ingredient comprises any one or a combination of insulin, an insulin analogue, a glycosidase inhibitor, a dipeptidyl peptidase IV inhibitor, a glucagon-like peptide-1 receptor agonist, a sodium-dependent glucose transporter-2 inhibitor, a sulfonylurea compound or a thiazolidinedione compound, preferably wherein the insulin comprises porcine insulin, human insulin or recombinant human insulin, preferably wherein the insulin analogue comprises insulin lispro, insulin aspart, insulin glargine or insulin detemir, preferably wherein the glycosidase inhibitor comprises acarbose, voglibose or miglitol, preferably, the dipeptidyl peptidase IV inhibitor comprises sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin, or tegagliptin, preferably, the glucagon-like peptide-1 receptor agonist comprises exenatide, belaglutide, liraglutide, loxapide, somaglutide, albiglutide, or dulaglutide, preferably, the sodium-dependent glucose transporter-2 inhibitor comprises canagliflozin, dapagliflozin, englipzin, rigagliflozin, or troglifloxagliflozin, preferably, the sulfonylurea compound comprises glibenclamide, glimepiride, gliclazide, glipizide, or gliquidone, preferably, the thiazolidinedione compound comprises rosiglitazone, troglitazone, ciglitazone, or glipizide.
9. Use of the oral composition according to any one of claims 1 to 3 for the preparation of a medicament for the treatment or prevention of hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, hyperlipidemia, diabetes with non-alcoholic fatty liver disease, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver disease.
10. Use of a pharmaceutical formulation according to any one of claims 4 to 9 in the manufacture of a medicament for the treatment or prevention of hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, hyperlipidemia, diabetes with non-alcoholic fatty liver disease, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver disease.
CN202210763080.0A 2022-06-30 2022-06-30 Oral composition Pending CN115192625A (en)

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WO2014008374A2 (en) * 2012-07-06 2014-01-09 Thetis Pharmaceuticals Llc Combination therapies comprising metformin salts and antihyperglycemia agents or antihyperlipidemia agents
CN103533833A (en) * 2011-01-12 2014-01-22 西蒂斯制药有限责任公司 Lipid-lowering antidiabetic agent
CN104684889A (en) * 2012-07-10 2015-06-03 西蒂斯制药有限责任公司 Tri-salt form of metformin

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US20130165679A1 (en) * 2011-12-22 2013-06-27 Kang Jian Biotech Corp., Ltd. Alpha-glucosidase inhibitor
WO2014008374A2 (en) * 2012-07-06 2014-01-09 Thetis Pharmaceuticals Llc Combination therapies comprising metformin salts and antihyperglycemia agents or antihyperlipidemia agents
CN104684889A (en) * 2012-07-10 2015-06-03 西蒂斯制药有限责任公司 Tri-salt form of metformin

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