CN116999398A - An oral composition - Google Patents

An oral composition Download PDF

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Publication number
CN116999398A
CN116999398A CN202310753650.2A CN202310753650A CN116999398A CN 116999398 A CN116999398 A CN 116999398A CN 202310753650 A CN202310753650 A CN 202310753650A CN 116999398 A CN116999398 A CN 116999398A
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active ingredient
soybean oil
insulin
weight ratio
diabetes
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Inventor
彭文
王峨县
孙磊
黄星
刘续征
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Hefei Tianhui Biotechnology Co ltd
Shandong Haibang Biotechnology Co ltd
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Hefei Tianhui Biotechnology Co ltd
Shandong Haibang Biotechnology Co ltd
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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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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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 eicosapentaenoate of phenformin, and the active ingredient and the soybean oil can reduce blood sugar in a synergistic way, so that the blood sugar reducing effect of the active ingredient can be remarkably improved.

Description

An 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 that severely threatens global health. The ninth version of IDF shows that 4.63 million adults currently have diabetes. If adequate countermeasures were not taken, by 2030, global diabetics would reach 5.78 million people and by 2045 would jump to a striking 7 million.
Biguanides are important drugs for the treatment of diabetes, and common biguanides include metformin and phenformin, which act by reducing liver glycogen production, inhibiting glucose absorption in the intestinal tract, and increasing peripheral resistance to glucose absorption and utilization, and increase insulin sensitivity by increasing peripheral sugar uptake and utilization.
Metformin is a primary medication in first-line and drug combination for controlling hyperglycemia in patients with T2DM and is recommended by guidelines for diabetes treatment in various countries around the world. The 2020 edition of Chinese guidelines for the prevention and treatment of type II diabetes indicates that metformin is currently the most commonly used hypoglycemic agent, has potential benefits beyond various hypoglycemic effects (such as treatment of cardiovascular diseases, diabetic cardiovascular complications, etc.), and does not increase the risk of hypoglycemia. If there is no contraindication, metformin should remain in the treatment regimen for diabetes.
The metformin can be used for treating type 2 diabetes with simple diet and physical exercise for controlling blood sugar inefficiency, and can also be used for treating with sulfonylurea drugs or insulin. The chemical formula of the metformin is:
it is therefore always a pursuit of the person skilled in the art if the therapeutic effect of eicosapentaenoic acid salts of metformin is 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 eicosapentaenoate of phenformin, and the active ingredient and the soybean oil can reduce blood sugar in a synergistic way, so that the blood sugar reducing effect of the active ingredient can be remarkably improved.
2. Technical proposal
In order to solve the problems, the invention adopts the following technical scheme.
In a first aspect the present invention provides an oral composition comprising an active ingredient comprising metformin and/or an eicosapentaenoate salt of phenformin and soybean oil.
Preferably, the weight ratio of the active ingredient to the soybean oil is 100: (50 to 1000), preferably 100: (50 to 400), preferably 100: (400-1000).
Preferably, the weight of the active ingredient and the soybean oil is
100mg of active ingredient
Soybean oil 50mg
Or (b)
100mg of active ingredient
Soybean oil 400mg
Or (b)
100mg of active ingredient
Soybean oil 1000mg.
In a second aspect, the present invention provides a pharmaceutical formulation comprising any of the above oral compositions and a pharmaceutically acceptable adjuvant.
Preferably, the pharmaceutical excipients comprise binders, disintegrants or lubricants, preferably, the pharmaceutical excipients further comprise diluents, emulsifiers, solubilizers, colorants, fragrances or sweeteners.
Preferably, the weight ratio of the binder, the lubricant and the disintegrating agent is:
adhesive 0-4
Lubricant 0-20
0 to 6 portions of disintegrating agent
Or (b)
Adhesive 0-3
Lubricant 0-10
0 to 3 portions of disintegrating agent
Or (b)
3 to 4 of adhesive
10 to 20 portions of lubricant
3 to 6 portions of disintegrating agent.
Preferably, 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 disintegrating agent is selected from one or more of carboxymethyl starch sodium, dry starch, low-substituted hydroxypropyl cellulose, crosslinked sodium carboxymethyl cellulose or crosslinked polyvinylpyrrolidone, preferably, the lubricant is selected from one or more of talcum powder, micro silica gel, 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 the use of a pharmaceutical formulation as described in any one of the above for the preparation of a medicament for the treatment or prophylaxis of hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, diabetes with non-alcoholic fatty liver, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver.
3. Advantageous effects
Compared with the prior art, the invention has the beneficial effects that:
(1) The oral composition of the invention can obviously improve the hypoglycemic effect of the eicosapentaenoate 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 salt of phenformin and soybean oil.
In one embodiment, the weight ratio of the 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 the active ingredient to soybean oil is 100:60.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:65.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:70.
in one embodiment, the weight ratio of the 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 the 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 the 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 the active ingredient to soybean oil is 100:110.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:120.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:130.
in one embodiment, the weight ratio of the 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 the 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 the active ingredient to soybean oil is 100:230.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:240.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:250.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:270.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:300.
in one embodiment, the weight ratio of the 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 the active ingredient to soybean oil is 100:430.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:450.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:470.
in one embodiment, the weight ratio of the 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 the 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 the active ingredient to soybean oil is 100:800.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:850.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:900.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:950.
in one embodiment, the weight ratio of the 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 the active ingredient to soybean oil is 100:4000.
in one embodiment, the weight ratio of the active ingredient to soybean oil is 100:5000.
in one embodiment, the weight ratio of the 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 weight is 10 mg/dose.
In one embodiment, the active ingredient weight is 20 mg/dose.
In one embodiment, the active ingredient weight is 30 mg/dose.
In one embodiment, the active ingredient weight is 40 mg/dose.
In one embodiment, the active ingredient weight is 50 mg/dose.
In one embodiment, the active ingredient weight is 70 mg/dose.
In one embodiment, the active ingredient weight is 100 mg/dose.
In one embodiment, the active ingredient weight is 130 mg/dose.
In one embodiment, the active ingredient weight is 200 mg/dose.
In one embodiment, the active ingredient weight is 250 mg/dose.
In one embodiment, the active ingredient weight is 300 mg/dose.
In one embodiment, the active ingredient weight is 400 mg/dose.
In one embodiment, the active ingredient weight is 500 mg/dose.
In one embodiment, the active ingredient weight is 600 mg/dose.
In one embodiment, the active ingredient weight is 700 mg/dose.
In one embodiment, the active ingredient weight is 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 1100 mg/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 weight is 1400 mg/dose.
In one embodiment, the active ingredient weight is 1500 mg/dose.
In one embodiment, the active ingredient weighs 1600 mg/dose.
In one embodiment, the active ingredient weight is 1700 mg/dose.
In one embodiment, the active ingredient weight is 1800 mg/dose.
In one embodiment, the active ingredient weighs 2000 mg/dose.
In one embodiment, the weight of the active ingredient and soybean oil is
100mg of active ingredient
Soybean oil 50mg
Or (b)
100mg of active ingredient
Soybean oil 400mg
Or (b)
100mg of active ingredient
Soybean oil 1000mg.
In a second aspect, the present invention provides a pharmaceutical formulation comprising any of the above oral compositions and a pharmaceutically acceptable adjuvant.
In one embodiment, the pharmaceutical excipients comprise a binder, disintegrant or lubricant, preferably, the pharmaceutical excipients further comprise a diluent, emulsifier, solubilizer, colorant, fragrance or sweetener.
In one embodiment, the binder, lubricant and disintegrant are present in a weight ratio of:
adhesive 0-4
Lubricant 0-20
0 to 6 portions of disintegrating agent
Or (b)
Adhesive 0-3
Lubricant 0-10
0 to 3 portions of disintegrating agent
Or (b)
3 to 4 of adhesive
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, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose or hydroxypropyl methyl cellulose, preferably, the disintegrating agent is selected from one or more of carboxymethyl starch sodium, 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, micro powder silica gel, magnesium lauryl sulfate, polyethylene glycol, magnesium dodecyl sulfate, stearic acid, calcium stearate or magnesium stearate.
In one embodiment, the pharmaceutical formulation is in the form of a tablet, capsule, powder, granule, capsule, pill, suppository, ointment, gel, aerosol, film, syrup, emulsion, suspension, or injection.
In a third aspect, the invention provides an oral composition as described in any one of the above, and the use of a pharmaceutical formulation as described in any one of the above for the preparation of a medicament for the treatment or prophylaxis of hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, diabetes with non-alcoholic fatty liver, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver.
Example 1
Preparation of metformin eicosapentaenoate
The structure of eicosapentaenoic acid is as follows
Commercial metformin hydrochloride is dissolved in 1mo/L aqueous sodium hydroxide solution, stirred for half an hour, ethanol is added, the solvent is removed by rotary evaporation, then ethanol is added, sodium chloride is removed by filtration, and the filtrate is rotary evaporated to obtain metformin free base.
Weighing 1mol of metformin free alkali, adding a proper amount of acetonitrile for dissolution, filtering to remove sodium chloride, slowly dripping 0.9mol of eicosapentaenoic acid solution (dissolved in acetonitrile) into the filtrate, stirring, cooling to 0-5 ℃, and filtering under the protection of nitrogen and in the absence of light to obtain light tan solid, namely the metformin eicosapentaenoic acid salt.
Example 2
Preparation of pharmaceutical compositions
Prescription (1000 pieces)
Raw and auxiliary materials Prescription quantity (g)
Metformin eicosapentaenoic acid salt 100
Soybean oil 50
Polyvinylpyrrolidone 3
Dodecyl sulfuric acidMagnesium (Mg) 10
Sodium carboxymethyl starch 6
Weighing raw materials and auxiliary materials according to the prescription amount, sieving 100g of metformin eicosapentaenoate with a 80-mesh sieve, adding 6g of carboxymethyl starch sodium, mixing, adding 50g of soybean oil and a polyvinylpyrrolidone water solution (prepared by 3g of polyvinylpyrrolidone and purified water) with the mass fraction of 3%, stirring uniformly, sieving, granulating, putting into a hot air circulation oven after granulating, drying at 50 ℃ for 0.5h, sieving with a 14-mesh sieve, finishing granulating, adding into a three-dimensional mixer after finishing granulating, adding 10g of magnesium dodecyl sulfate, 50 revolutions per minute, mixing for 1h, finishing mixing, and tabletting to obtain the metformin eicosapentaenoate soybean oil composition.
Example 3
Preparation of pharmaceutical compositions
Prescription (1000 capsules)
Weighing the raw materials and the auxiliary materials according to the prescription, sieving 100g of metformin eicosapentaenoic acid salt with a 80-mesh sieve, adding 400g of soybean oil, uniformly stirring, and filling into capsules after the mixing is finished to obtain the metformin eicosapentaenoic acid salt soybean oil composition.
Example 4
Preparation of pharmaceutical compositions
Prescription (1000 pieces)
Raw and auxiliary materials Prescription quantity (g)
Metformin eicosapentaenoic acid salt 100
Soybean oil 1000
Polyvinylpyrrolidone 4
Magnesium stearate 20
Sodium carboxymethyl starch 3
Weighing raw materials and auxiliary materials according to the prescription amount, sieving 100g of metformin eicosapentaenoate with a 80-mesh sieve, adding 3g of carboxymethyl starch sodium, mixing, adding 1000g of soybean oil and 5% by mass of polyvinylpyrrolidone aqueous solution (prepared from 4g of polyvinylpyrrolidone and purified water), stirring uniformly, sieving, granulating, putting into a hot air circulation oven after granulating is finished, drying at 60 ℃ for 1h, sieving with a 14-mesh sieve, finishing granulating, adding into a three-dimensional mixer, adding 20g of magnesium stearate, 50 revolutions per minute, mixing for 1h, finishing mixing, tabletting, and obtaining the metformin eicosapentaenoate soybean oil composition.
Example 5
Animal experiment
The experimental method comprises the following steps:
establishment of diabetes model mice:
70 rats are fasted for 6 hours, and are injected with streptozotocin intraperitoneally at the dosage of 40mg/kg once a day, and are fed with high-fat feed, and the fasting blood glucose is measured by a Roche glucometer, and the fasting blood glucose value is more than 11.1mmol/L, so that the molding is successful. Model mice were randomly divided into 6 groups of 10 mice each. Another 10 non-model rats were taken as a normal control group.
Experimental grouping:
normal control group: 10 normal rats without molding are subcutaneously injected with physiological saline;
model control group: 10 model mice were subcutaneously injected with physiological saline;
drug group:
the pharmaceutical compositions prepared in examples 1-4 were administered before each group had been given the gastric-unaged drug, the fasting blood glucose was measured with a glucometer, each group had been given the gastric-unaged drug, and after each group had been given the drug, the drug was given the following free water and was fed with the high-fat feed, and after the 10d administration, the tail was cut to obtain blood, and the blood glucose of each rat was measured with the glucometer to obtain the average blood glucose value of the corresponding group of 10 rats, with the following specific dosing regimen:
group A: 10 model rats were given the pharmaceutical composition prepared in example 2 by gavage at 20mg/kg of body weight of the rats once daily for 10 consecutive days;
group B: 10 model rats were given the pharmaceutical composition prepared in example 3 by gavage at 20mg/kg of body weight of the rats once daily for 10 consecutive days;
group C: the pharmaceutical composition prepared in example 4 was administered once daily for 10 consecutive days in 10 model rats by gavage of 20mg/kg rat body weight;
group D: model 10 mice were dosed once daily for 10 consecutive days with metformin eicosapentaenoic acid salt prepared in example 1 by gavage of 20mg/kg of rat body weight;
group E: the model rats were given 10 rats per day with soybean oil commercially available by gavage at 20mg/kg of body weight for 10 consecutive days.
The experimental results are shown in the following table
Time/group 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 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, P <0.01 in the normal control group compared with the model control group indicates that the diabetes modeling is successful.
The E group has no obvious difference from the model control group, and shows that the soybean oil alone has poor hypoglycemic effect.
Group a, group B, group C, group D have P <0.01 compared to the model control group.
Group a, group B, group C and group D compare with P <0.05.
Therefore, the combined use of the metformin eicosapentaenoate and the soybean oil can achieve remarkable hypoglycemic effect and play a synergistic effect.

Claims (10)

1. An oral composition comprising an active ingredient and soybean oil, the active ingredient comprising metformin and/or a salt of eicosapentaenoic acid of phenformin, the weight ratio of the active ingredient to the soybean oil being 100: (50-1000).
2. The oral composition of claim 1, wherein the weight ratio of active ingredient to soybean oil is 100: (50 to 400), preferably 100: (400-1000).
3. The oral composition of claim 1, wherein the weight of the active ingredient and soybean oil is
100mg of active ingredient
Soybean oil 50mg
Or (b)
100mg of active ingredient
Soybean oil 400mg
Or (b)
100mg of active ingredient
Soybean oil 1000mg.
4. Pharmaceutical formulation, characterized in that it comprises an oral composition according to any one of claims 1 to 3 and a pharmaceutical adjuvant.
5. The pharmaceutical formulation according to claim 4, wherein the pharmaceutical excipients comprise binders, disintegrants or lubricants, preferably the pharmaceutical excipients further comprise diluents, emulsifiers, solubilizers, colorants, fragrances or sweeteners.
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, micro powder silica gel, magnesium lauryl sulfate, polyethylene glycol, magnesium lauryl sulfate, stearic acid, calcium stearate or magnesium stearate.
7. The pharmaceutical formulation according to any one of claims 4 to 6, wherein the pharmaceutical formulation is in the form of a tablet, capsule, powder, granule, capsule, pill, suppository, ointment, gel, aerosol, film, syrup, emulsion, suspension or injection.
8. The pharmaceutical formulation according to any one of claims 4-7, further comprising a second active ingredient, which is a hypoglycemic drug, preferably, the second active ingredient comprises any one or a combination of insulin, insulin analogues, glycosidase inhibitors, dipeptidyl peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, sodium dependent glucose transporter-2 inhibitors, sulfonylurea compounds or thiazolidinediones, preferably, the insulin comprises porcine insulin, human insulin or recombinant human insulin, preferably, the insulin analogues comprise insulin lispro, insulin aspart, insulin glargine or insulin deltoid, preferably, the glycosidase inhibitors comprise acarbose, voglibose or miglitol, preferably, the dipeptidyl peptidase IV inhibitor comprises sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin, gemagliptin or tigliptin, preferably, the glucagon-like peptide-1 receptor agonist comprises exenatide, bei Lalu peptide, liraglutide, loxinaide, somalunin, abilutide or duloxetide, preferably, the sodium-dependent glucose transporter-2 inhibitor comprises canagliflozin, dapagliflozin, engagliflozin, exeagliflozin, lugliflozin or tolagliflozin, preferably, the sulfonylurea compound comprises glibenclamide, glimepiride, gliclazide, glipizide or gliquidone, preferably, the thiazolidinedione compound comprises rosiglitazone, troglitazone, cyclic glitazone or pioglitagliquidone.
9. Use of an oral composition according to any one of claims 1-3 for the preparation of a medicament for the treatment or prophylaxis of hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, hyperlipidemia, diabetes with non-alcoholic fatty liver, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver.
10. Use of a pharmaceutical formulation according to any one of claims 4-9 for the preparation of a medicament for the treatment or prophylaxis of hyperglycemia, type 2 diabetes, type 1 diabetes, obesity, impaired glucose tolerance, hyperlipidemia, diabetes with non-alcoholic fatty liver, diabetic cardiovascular disease, cardiovascular disease or non-alcoholic fatty liver.
CN202310753650.2A 2022-06-30 2022-06-30 An oral composition Pending CN116999398A (en)

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US20120178813A1 (en) * 2011-01-12 2012-07-12 Thetis Pharmaceuticals Llc Lipid-lowering antidiabetic agent
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