Pharmaceutical composition as well as application and medicament thereof

Abstract

The invention provides a pharmaceutical composition as well as application and a medicament thereof. The pharmaceutical composition comprises 5%-85% of a gymnema sylvestre extract, 5%-85% of a balsam pear extract, 5%-85% of a turmeric extract and 5%-85% of a wood orange extract. % is the mass percentage of each component in the pharmaceutical composition. The pharmaceutical composition provides significant benefits in managing diabetes, hyperlipidemia and associated metabolic disorders.

Description

TECHNICAL FIELD

[0001] The present invention relates to a pharmaceutical composition and its use and medicament. BACKGROUND

[0002] Diabetes mellitus is a chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood glucose. Hyperglycemia, also known as elevated blood glucose, is a common consequence of uncontrolled diabetes and, over time, can cause serious damage to many of the body's systems, especially the nerves and blood vessels.

[0003] According to the World Health Organization (WHO), the number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. In low- and middle-income countries, rates of increase are higher than in high-income countries. Between 2000 and 2019, diabetes mortality increased by 3%. In 2019, diabetes and kidney disease caused by diabetes were estimated to have caused 20 million deaths. A healthy diet, regular physical activity, maintaining a normal body weight, and avoiding tobacco use are ways to prevent or delay the onset of type 2 diabetes. Diabetes can be treated and its consequences avoided or delayed with diet, physical activity, appropriate medications, regular screening, and treatment of complications.

[0004] In addition, hyperlipidemia (also known as high cholesterol) can be defined as a variety of diseases caused by an excess of fat (lipids) in the blood. These lipids can enter the walls of the arteries, increasing the risk of arteriosclerosis, which can lead to complications of hyperlipidemia such as heart disease or stroke. Hyperlipidemia can also be a cause of cardiovascular disease. Therefore, it is important to control hyperlipidemia through lifestyle changes and appropriate medications.

[0005] Metabolism is the process by which the human body obtains energy from food. Food is composed of proteins, carbohydrates, and fats. Chemicals in the digestive system break down parts of the food into sugars and acids, which serve as fuel. The body can use this fuel immediately, or it can store energy in body tissues, such as the liver, muscles, and body fat, for later use.

[0006] In addition, metabolic disorders occur when abnormal chemical reactions in the body disrupt the metabolic process. When a metabolic disorder occurs, the human body can have too much of certain substances or too little of other substances needed to maintain health. These diseases come in various types. Some affect the breakdown of amino acids, carbohydrates, or lipids. Another class, mitochondrial diseases, affects the part of the cell that produces energy.

[0007] There is growing interest in the use of natural therapies to treat diabetes, hyperlipidemia, and metabolic disorders. Natural therapies to treat diabetes, hyperlipidemia, and metabolic disorders are of great interest due to the potential for fewer side effects and additional health benefits.

[0008] Diabetes, hyperlipidemia, and general metabolic disorders affect a significant portion of the global population. Traditionally, synthetic drugs have been used to treat health conditions such as diabetes, hyperlipidemia, and metabolic disorders. Synthetic drugs are chemical compounds created through chemical synthesis, designed to mimic the effects of natural substances or to produce a specific pharmacological effect. Synthetic drugs are created in a laboratory through chemical processes, rather than being extracted from natural sources.

[0009] There are multiple drawbacks to using synthetic drugs to treat conditions such as diabetes, hyperlipidemia, and metabolic disorders. First, synthetic drugs often have a range of side effects, including gastrointestinal issues, muscle pain, and fatigue, impacting the quality of life for patients. Additionally, a few synthetic drugs, particularly those used to manage diabetes, carry the risk of hypoglycemia. If not managed properly, hypoglycemia is a dangerous condition. Furthermore, the cost of synthetic drugs can be high, placing financial strain on patients, particularly those with inadequate insurance coverage. Synthetic drugs can also interact with other medications or supplements, leading to adverse reactions or reduced effectiveness. Long-term use of synthetic drugs can be associated with health risks such as cardiovascular events or liver problems, further complicating treatment. Finally, poor adherence to medication regimens can undermine the effectiveness of synthetic drugs, highlighting the need for a holistic approach to managing these conditions.

[0010] Therefore, there is a need for a composition comprising a combination of natural ingredients to treat diabetes, hyperlipidemia, and metabolic disorders to address the aforementioned issues. SUMMARY

[0011] This summary is intended to introduce selected concepts in a simplified form to provide a basic understanding of the concepts further described in the disclosure. This summary is not intended to identify key or essential inventive concepts or to delineate the scope of the disclosure.

[0012] To address the lack of drugs containing natural ingredients that can treat diabetes, hyperlipidemia, and metabolic disorders in the prior art, the present invention provides a pharmaceutical composition, its use, and a medicament. Clinical studies have shown that the pharmaceutical composition provides significant benefits in managing diabetes, hyperlipidemia, and related metabolic disorders.

[0013] The present invention provides a pharmaceutical composition comprising: an extract of Gymnema sylvestre 5%-85%, an extract of Momordica charantia 5%-85%, an extract of Curcuma longa 5%-85%, and an extract of Aegle marmelos 5%-85%; wherein % is the mass percentage of each component in the pharmaceutical composition.

[0014] In some embodiments, the pharmaceutical composition comprises: extract of Gymnema sylvestre 15-40%, extract of Momordica charantia 15-35%, extract of Curcuma longa 10-30%, and extract of Clausena lansium 15-35%.

[0015] In specific embodiments, the pharmaceutical composition comprises: extract of Gymnema sylvestre 25-35%, extract of Momordica charantia 20-30%, extract of Curcuma longa 15-35%, and extract of Clausena lansium 20-25%.

[0016] In a certain embodiment, the pharmaceutical composition is formulated as follows: extract of Gymnema sylvestre 30%, extract of Momordica charantia 25%, extract of Curcuma longa 20%, extract of Clausena lansium 25%.

[0017] In a certain embodiment, the pharmaceutical composition is formulated as follows: extract of Gymnema sylvestre 25%, extract of Momordica charantia 20%, extract of Curcuma longa 35%, extract of Clausena lansium 20%.

[0018] In a certain embodiment, the pharmaceutical composition is formulated as follows: extract of Gymnema sylvestre 35%, extract of Momordica charantia 30%, extract of Curcuma longa 15%, extract of Clausena lansium 20%.

[0019] In some embodiments, the extract of Gymnema sylvestre contains at least 25% of gymnemic acids, % refers to the mass percentage of gymnemic acids in the extract of Gymnema sylvestre.

[0020] In specific embodiments, the extract of Gymnema sylvestre contains 25% of gymnemic acids, % refers to the mass percentage of gymnemic acids in the extract of Gymnema sylvestre.

[0021] In some embodiments, the extract of Momordica charantia contains at least 2.5% of charantin, and at least 10% of Momordica charantia polypeptide, % refers to the mass percentage of each active ingredient in the extract of Momordica charantia.

[0022] In specific embodiments, the extract of Momordica charantia contains 2.5% of charantin, and 10% of Momordica charantia polypeptide, % refers to the mass percentage of each active ingredient in the extract of Momordica charantia.

[0023] In some embodiments, the extract of Curcuma longa contains at least 95% of curcuminoids, % refers to the mass percentage of curcuminoids in the extract of Curcuma longa.

[0024] In specific embodiments, the extract of Curcuma longa contains 95% of curcuminoids, % refers to the mass percentage of curcuminoids in the extract of Curcuma longa.

[0025] In some embodiments, the extract of Phyllanthus emblica contains at least 1.5% of marmelosin and at least 3% of total flavonoids, % refers to the mass percentage of each active ingredient in the extract of Phyllanthus emblica.

[0026] In specific embodiments, the extract of Phyllanthus emblica contains 1.5% of marmelosin and 3% of total flavonoids, % refers to the mass percentage of each active ingredient in the extract of Phyllanthus emblica.

[0027] In some embodiments, the extraction solvent of the extract of Phyllanthus emblica, the extract of Momordica charantia, the extract of Curcuma longa and the extract of Clausena lansium is one or more of water, ethanol, methanol, a mixture of water and alcohol, supercritical fluid and ionic liquid.

[0028] In the present application, the content of the above-mentioned active ingredients in each of the extracts is controlled to ensure the stability and predictability of the therapeutic effect.

[0029] In some embodiments, the preparation method of the pharmaceutical composition comprises the following steps in sequence: harvesting raw materials of each of the extracts; then washing, drying, grinding, extracting and concentrating each of the raw materials, respectively; and then mixing the preparations; the raw materials include Phyllanthus emblica leaves, Momordica charantia, Curcuma longa and Clausena lansium.

[0030] In the present application, the extraction and concentration method can be one or more of evaporation, distillation, freeze concentration, ultrafiltration, nanofiltration and reverse osmosis.

[0031] In the present application, the drying method can be one or more of spray drying, freeze drying, vacuum drying, drum drying, tray drying, air drying, sunlight drying, oven drying, microwave drying and infrared drying until the desired moisture content is reached.

[0032] In the present application, the grinding method can be one or more of mechanical grinding, ball milling, jet milling, cryogenic grinding, hammer milling and pin milling to obtain a powder with a specific particle size range.

[0033] In the present application, it is known to those skilled in the art that the extraction and concentration process also includes separation to obtain a purified fraction.

[0034] The separation step generally includes chromatography, distillation, crystallization and precipitation.

[0035] In the present application, after the extraction and concentration process, a packaging process for each extract can also be included to preserve the effective chemical components in each raw material, which ensures the stability and efficacy of active compounds in natural ingredients and provides a convenient and effective delivery method.

[0036] The encapsulating step generally includes chromatography, distillation, crystallization, spray drying, extrusion, coacervation, liposome and encapsulation.

[0037] In a specific embodiment, the harvest maturity standard of the Gymnema leaves is that the Gymnema leaves grow for 3-4 months; the chlorophyll content of the Gymnema leaves is 20-25 mg / g, and the total glycoside content of the Gymnema leaves is 6%-8%, which means that the mass percentage of all types of glycosides in the Gymnema leaves accounts for the total mass of the Gymnema leaves. The harvest maturity standard belongs to the best maturity of the Gymnema leaves, which are fully unfolded but not yet beginning to age. The glycosides in the Gymnema leaves include triterpene saponins, glycosides and the like.

[0038] In a specific embodiment, after the cleaning and drying step, the moisture content of the Gymnema leaves is 5%-8%, which means that the mass percentage of water in the Gymnema leaves accounts for the total mass of the Gymnema leaves. When the moisture content is too high, it will lead to the breeding of microorganisms and the degradation of active ingredients, and when the moisture content is too low, it will lead to the loss of some heat-sensitive ingredients. Within the above control range, the stability of the Gymnema leaves and the preservation of active ingredients can be ensured.

[0039] In a specific embodiment, the cleaned and dried Gymnema leaves are ground to obtain Gymnema leaf powder, and the particle size of the Gymnema leaf powder is 40-60 μm. Within this particle size range, the full contact of the solvent and the Gymnema leaf powder in the extraction process can be ensured, and at the same time, the formation of a sedimentation layer or the clogging of a filter by the fine powder in the extraction process can be avoided.

[0040] In the present application, the following special extraction method can be used to enrich and concentrate gymnemic acid in Gymnema.

[0041] In a specific embodiment, the extraction method of the Gymnema extract includes a gradient temperature ultrasonic-assisted extraction method, which includes the following steps: taking 70% ethanol aqueous solution as a first extraction solvent, mixing the Gymnema leaf powder with the first extraction solvent, and the mass ratio of the first extraction solvent to the Gymnema leaf powder is 8:1; extracting at 35°C for 1 hour, and then increasing the temperature to 50±2°C for 4 hours; the ultrasonic power and frequency of the ultrasonic-assisted extraction method are 600 W and 45 kHz, respectively. Compared with the traditional reflux extraction, the extraction rate of gymnemic acid in the Gymnema leaves can be increased by 43% by using the extraction method.

[0042] In a specific embodiment, the harvest maturity standard of the Momordica charantia is that the Momordica charantia is pollinated for 15-20 days, and the fruit length is 15-20 cm; the content of charantin in the Momordica charantia is 0.8%-1.2%, which means that the mass percentage of charantin accounts for the total mass of the Momordica charantia. The harvest maturity standard belongs to the best maturity of the Momordica charantia, and the skin is bright green and shiny, and the flesh is firm.

[0043] In a specific embodiment, the moisture content of the washed and dried Momordica charantia is 4%-7%, % refers to the percentage of water in the mass of Momordica charantia; when the moisture content is too high, it will lead to the breeding of microorganisms and the degradation of active ingredients, while when the moisture content is too low, it may lead to the loss of some heat-sensitive ingredients. Within the above control range, the stability of Momordica charantia and the preservation of active ingredients can be ensured.

[0044] In a specific embodiment, the washed and dried Momordica charantia is ground to obtain Momordica charantia powder, and the particle size of the Momordica charantia powder is 60-80 μm; within this particle size range, it can ensure sufficient contact between the solvent and the Momordica charantia powder during extraction, while avoiding the formation of a sedimentation layer or the clogging of the filter by too fine powder during extraction.

[0045] In the present application, the following special extraction method can be used to enrich and concentrate momordin and Momordica charantia polypeptide in Momordica charantia.

[0046] In a specific embodiment, the extraction method of the extract of Momordica charantia comprises a pulse negative pressure cyclic extraction method, which comprises the following steps: first mixing the Momordica charantia powder with a second extraction solvent of 60% ethanol aqueous solution, and the mass ratio of the second extraction solvent to the Momordica charantia powder is 10:1; extracting at 45±2℃, setting the negative pressure to-0.08 MPa, and the pulse cycle to 5 minutes of negative pressure / 2 minutes of normal pressure, and the total cycle is 6 hours. This extraction method can increase the extraction rate of momordin and Momordica charantia polypeptide in Momordica charantia by 35%.

[0047] In a specific embodiment, the harvesting maturity standard of Curcuma longa is: Curcuma longa with a planting time of 8-10 months and a rhizome diameter of ≥2.5 cm; the content of curcumin in Curcuma longa is ≥3.5%, % refers to the percentage of curcumin in the mass of Curcuma longa. This harvesting maturity standard belongs to the best maturity of Curcuma longa, which presents orange yellow after being cut open.

[0048] In a specific embodiment, the moisture content of the washed and dried Curcuma longa is 6%-9%, % refers to the percentage of water in the mass of Curcuma longa; when the moisture content is too high, it will lead to the breeding of microorganisms and the degradation of active ingredients, while when the moisture content is too low, it may lead to the loss of some heat-sensitive ingredients. Within the above control range, the stability of Curcuma longa and the preservation of active ingredients can be ensured.

[0049] In a specific embodiment, the washed and dried Curcuma longa is ground to obtain Curcuma longa powder, and the particle size of the Curcuma longa powder is 30-50 μm; within this particle size range, it can ensure sufficient contact between the solvent and the Curcuma longa powder during extraction, while avoiding the formation of a sedimentation layer or the clogging of the filter by too fine powder during extraction.

[0050] In the present application, the following special extraction method can be used to enrich and concentrate curcuminoids in turmeric.

[0051] In a specific embodiment, the extraction method of the turmeric extract comprises a microemulsion-assisted extraction method, which comprises the following steps: mixing the turmeric powder with a third extraction solvent, which is an 80% ethanol aqueous solution, at a mass ratio of 6:1; and extracting at 55±2℃ for 4 hours. This extraction method can increase the extraction rate of curcuminoids in turmeric by 35% and enhance the solubility and stability of curcuminoids.

[0052] In a specific embodiment, the harvest maturity standard of the Clausena lansium is that the Clausena lansium is harvested 150-180 days after flowering and the fruit diameter is 8-10 cm, and the content of decursinol in the Clausena lansium is 1.0%-1.5%, which is the mass percentage of decursinol in the Clausena lansium. This harvest maturity standard belongs to the optimal maturity of the Clausena lansium, and the peel of the Clausena lansium turns light yellow but has not yet fully matured.

[0053] In a specific embodiment, after the cleaning and drying step, the moisture content of the Clausena lansium is 5%-8%, which is the mass percentage of water in the Clausena lansium. When the moisture content is too high, it can cause the growth and activity of microorganisms and the degradation of active ingredients, and when the moisture content is too low, it can cause the loss of some heat-sensitive ingredients. Within the above control range, the stability of the Clausena lansium and the preservation of active ingredients can be ensured.

[0054] In a specific embodiment, the cleaned and dried Clausena lansium is ground to obtain a Clausena lansium powder, and the particle size of the Clausena lansium powder is 50-70 μm. Within this particle size range, the solvent can fully contact the Clausena lansium powder during the extraction process, and at the same time, the formation of a sedimentation layer or the clogging of the filter by the fine powder during the extraction process can be avoided.

[0055] In the present application, the following special extraction method can be used to enrich and concentrate decursinol in Clausena lansium.

[0056] In a specific embodiment, the extraction method of the Clausena lansium extract comprises a dual-phase extraction method of supercritical CO2 fluid and ethanol, which comprises the following steps: mixing the Clausena lansium powder with a fourth extraction solvent, which is a 65% ethanol aqueous solution, at a mass ratio of 7:1; first extracting the fat-soluble ingredients with supercritical CO2 for 2 hours, and then extracting the water-soluble ingredients with the 65% ethanol aqueous solution for 3.5 hours; and the pressure and temperature of the supercritical CO2 are 20 MPa and 40℃, respectively. This extraction method can comprehensively obtain active ingredients of different polarities in the Clausena lansium.

[0057] In the present application, the cellulose, pectin and the like in the raw material of each extract can be removed by the above preparation method, which can reduce the bioavailability of the active ingredient.

[0058] The present application also provides a use of the pharmaceutical composition as described above in the treatment of diabetes, hyperlipidemia and metabolic disorder.

[0059] The present application also provides a medicament comprising the pharmaceutical composition as described above; the dosage form of the medicament is one or more of tablet, capsule, powder, granule, suspension, emulsion, gel, cream and lotion.

[0060] In the present application, the medicament can be prepared in oral administration form, and the daily dosage ranges from 500 milligrams (mg) to 2 grams (g).

[0061] On the basis of common general knowledge in the art, the above preferred conditions can be combined at will, thereby obtaining each preferred example of the present application.

[0062] The reagents and raw materials used in the present application are commercially available.

[0063] The positive progress effect of the present application is that:

[0064] 1. The pharmaceutical composition of the present application provides significant benefits in the management of diabetes, improvement of hyperlipidemia and improvement of metabolic disorder; specifically,

[0065] Regarding the management of diabetes: the fasting blood glucose is reduced by an average of 30%-35%, the 2-hour postprandial blood glucose is reduced by 35%-40%, the glycosylated hemoglobin (HbA1c) is reduced by 1.5-2.0 percentage points, the insulin sensitivity is increased by 45%-50%, and the β-cell function improvement index (HOMA-β) is increased by 35%-40%;

[0066] Regarding the improvement of hyperlipidemia: the total cholesterol is reduced by 30%-35%, the LDL cholesterol is reduced by 35%-40%, the triglyceride is reduced by 35%-40%, the HDL cholesterol is increased by 18%-22%, and the atherosclerosis index is improved by 40%-45%;

[0067] Regarding the improvement of metabolic indicators: the body mass index (BMI) is reduced by 5-8%, the waist circumference is reduced by 4-6 cm, the liver function indicators (ALT, AST) are improved by 25-30%, the inflammation markers (CRP, IL-6) are reduced by 40-45%, and the oxidative stress markers are reduced by 45-50%.

[0068] 2. The pharmaceutical composition also has the following effects: ① optimizing multiple insulin signaling pathways, ② comprehensively regulating liver metabolism, ③ regulating multiple links of lipid metabolism, ④ synergistic effect of anti-inflammatory and antioxidant. DETAILED DESCRIPTION

[0069] In this document, the term "exemplary" is used to mean "an example of" or "an example, not necessarily a preferred or advantageous example." Any implementation of the subject matter in this specification is not necessarily to be construed as preferred or advantageous over other implementations.

[0070] The terms "comprises", "comprising", or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a device or a subsystem or element or a structure or a component that comprises a list of one or more devices, sub-systems, elements, structures, or components, any of which is not mutually exclusive, does not preclude the existence of other devices, sub-systems, additional sub-modules, or elements. The terms "in one embodiment", "in another embodiment", and similar language in this specification may appear, but are not necessarily all referring to the same embodiment.

[0071] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0072] Embodiment 1

[0073] The present embodiment discloses a pharmaceutical composition, which is composed of the following components:

[0074] 30% of extract of Gymnema sylvestre, 25% of extract of Momordica charantia, 20% of extract of Curcuma longa, and 25% of extract of Melia toosendan; wherein % is the mass percentage of each component in the pharmaceutical composition.

[0075] The extract of Gymnema sylvestre contains 25% of gymnemic acid, and % means the mass percentage of gymnemic acid in the extract of Gymnema sylvestre;

[0076] The preparation method of the extract of Gymnema sylvestre comprises the following steps in sequence: harvesting Gymnema sylvestre leaves; and then cleaning, drying, grinding, extracting and concentrating the Gymnema sylvestre leaves. The maturity standard of the harvested Gymnema sylvestre leaves is that the Gymnema sylvestre leaves are grown for 3-4 months. The chlorophyll content of the Gymnema sylvestre leaves is 20-25 mg / g. The total glycoside content of the Gymnema sylvestre leaves is 6%-8%, and % means the mass percentage of all types of glycosides in the Gymnema sylvestre leaves. After the cleaning and drying step, the water content of the Gymnema sylvestre leaves is 5%-8%, and % means the mass percentage of water in the Gymnema sylvestre leaves. The cleaned and dried Gymnema sylvestre leaves are ground to obtain Gymnema sylvestre leaf powder, and the particle size of the Gymnema sylvestre leaf powder is 40-60 μm. The extraction method of the extract of Gymnema sylvestre is a gradient temperature ultrasonic-assisted extraction method, which comprises the following steps: using 70% ethanol aqueous solution as the first extraction solvent, mixing the Gymnema sylvestre leaf powder with the first extraction solvent, and the mass ratio of the first extraction solvent to the Gymnema sylvestre leaf powder is 8:1; extracting at 35°C for 1 hour, and then increasing the temperature to 50±2°C for 4 hours; the ultrasonic power and frequency of the ultrasonic-assisted extraction method are 600 W and 45 kHz, respectively.

[0077] The extract of Momordica charantia contains 2.5% charantin and 10% Momordica charantia polypeptide, % referring to the mass percentage of each active ingredient in the extract of Momordica charantia.

[0078] The preparation method of the extract of Momordica charantia comprises the following steps in sequence: harvesting Momordica charantia; and then cleaning, drying, grinding and extracting and concentrating the Momordica charantia. The harvesting maturity standard of the Momordica charantia is that the Momordica charantia is 15-20 days after pollination and the fruit length is 15-20 cm; the charantin content of the Momordica charantia is 0.8%-1.2%, % referring to the mass percentage of charantin in the Momordica charantia; after the cleaning and drying step, the water content of the Momordica charantia is 4%-7%, % referring to the mass percentage of water in the Momordica charantia; the cleaned and dried Momordica charantia is ground to obtain Momordica charantia powder, and the particle size of the Momordica charantia powder is 60-80 μm; the extraction method of the extract of Momordica charantia is pulse negative pressure circulation extraction, which comprises the following steps: 60% ethanol aqueous solution is used as a second extraction solvent, the Momordica charantia powder is mixed with the second extraction solvent, and the mass ratio of the second extraction solvent to the Momordica charantia powder is 10:1; extraction is carried out at 45±2 ℃, the negative pressure is set to be -0.08 MPa, the pulse cycle is 5 minutes of negative pressure / 2 minutes of normal pressure, and the total cycle is 6 hours.

[0079] The extract of Curcuma longa contains 95% curcumin compounds, % referring to the mass percentage of curcumin compounds in the extract of Curcuma longa.

[0080] The preparation method of the extract of Curcuma longa comprises the following steps in sequence: harvesting Curcuma longa; and then cleaning, drying, grinding and extracting and concentrating the Curcuma longa. The harvesting maturity standard of the Curcuma longa is that the Curcuma longa is planted for 8-10 months and the rhizome diameter is ≥2.5 cm; the curcumin content of the Curcuma longa is ≥3.5%, % referring to the mass percentage of curcumin in the Curcuma longa; after the cleaning and drying step, the water content of the Curcuma longa is 6%-9%, % referring to the mass percentage of water in the Curcuma longa; the cleaned and dried Curcuma longa is ground to obtain Curcuma longa powder, and the particle size of the Curcuma longa powder is 30-50 μm; the extraction method of the extract of Curcuma longa is microemulsion assisted extraction, which comprises the following steps: 80% ethanol aqueous solution is used as a third extraction solvent, the Curcuma longa powder is mixed with the third extraction solvent, and the mass ratio of the third extraction solvent to the Curcuma longa powder is 6:1; extraction is carried out at 55±2 ℃ for 4 hours.

[0081] The extract of Clausena lansium contains 1.5% marmelosin and 3% total flavonoids, % referring to the mass percentage of each active ingredient in the extract of Clausena lansium.

[0082] The preparation method of the extract of Fortunella crassifolia includes the following steps in sequence: harvesting Fortunella crassifolia; then cleaning, drying, grinding and extracting and concentrating the Fortunella crassifolia. The maturity standard for harvesting the Fortunella crassifolia is that the Fortunella crassifolia is 150-180 days after flowering and the diameter of the fruit is 8-10 cm, and the content of isoaromadendrin in the Fortunella crassifolia is 1.0%-1.5%, wherein the percentage refers to the mass percentage of isoaromadendrin in the Fortunella crassifolia; after the cleaning and drying step, the water content of the Fortunella crassifolia is 5%-8%, wherein the percentage refers to the mass percentage of water in the Fortunella crassifolia; the cleaned and dried Fortunella crassifolia is ground to obtain Fortunella crassifolia powder, and the particle size of the Fortunella crassifolia powder is 50-70 μm; the extraction method of the extract of Fortunella crassifolia is a dual-phase extraction method of supercritical CO2 fluid and ethanol, which includes the following steps: 65% ethanol aqueous solution is used as the fourth extraction solvent, the Fortunella crassifolia powder is mixed with the fourth extraction solvent, and the mass ratio of the fourth extraction solvent to the Fortunella crassifolia powder is 7:1; the fat-soluble components are extracted by supercritical CO2 for 2 hours, and then the water-soluble components are extracted by 65% ethanol aqueous solution for 3.5 hours; the pressure and the temperature of the supercritical CO2 are 20 MPa and 40°C respectively.

[0083] The preparation method of the pharmaceutical composition of the embodiment includes the preparation steps of the above extracts and the following steps:

[0084] The above extracts are respectively subjected to a reduced-pressure concentration operation again, concentrated to a relative density of 1.05-1.10 (25°C) g / cm3, and then subjected to spray drying (inlet temperature 145±5°C, outlet temperature 85±5°C, atomization pressure 2.5 MPa) to obtain standardized extract powder.

[0085] The extracts are mixed in proportion, 2% silicon dioxide is added as an anti-caking agent, and the mixture is encapsulated by HPMC capsules, each capsule containing 500 mg of total extract.

[0086] Example 2

[0087] The embodiment discloses a pharmaceutical composition, which belongs to a high-curcumin formula and is composed of the following components: extract of Gymnema sylvestre 25%, extract of Momordica charantia 20%, extract of Curcuma longa 35%, and extract of Fortunella crassifolia 20%; wherein the percentages are mass percentages of the components in the pharmaceutical composition.

[0088] The preparation method of the extract of Curcuma longa further introduces a purification process after the extraction step of Curcuma longa based on the preparation method of Example 1, the content of curcumin in the extract of Curcuma longa is increased to more than 95% by molecular sieve chromatography, and the bioavailability is improved by phospholipid complexation technology. The other preparation methods of the pharmaceutical composition are the same as those of Example 1.

[0089] The final product is prepared into sustained-release tablets, each tablet containing 600 mg of total extract and being uniformly released within 24 hours.

[0090] Example 3

[0091] The present embodiment discloses a pharmaceutical composition, which belongs to the category of islet beta cell protection and enhancement formula, and is composed of the following components: extract of Gymnema sylvestre 35%, extract of Momordica charantia 30%, extract of Curcuma longa 15%, and extract of Melia toosendan 20%; wherein the percentage is the mass percentage of each component in the pharmaceutical composition.

[0092] The preparation process of the pharmaceutical composition is as follows: each extract is separately subjected to nano-emulsification technology, and each extract is mixed with medium-chain triglyceride and lecithin at a ratio of 1:2:0.5, high-pressure homogenization (80 MPa, 3 cycles) is performed to form nano-emulsion with a particle size of <200 nm, freeze-drying is performed to prepare powder, and the powder is loaded into enteric-coated capsules to ensure the release of active ingredients in the small intestine region.

[0093] The pharmaceutical compositions of embodiments 1-3 contain natural ingredients for the treatment of diabetes, hyperlipidemia, and related metabolic disorders. The natural ingredients prevent adverse effects, further inhibit dependence and drug resistance problems, reduce economic burden, and protect the environment. The pharmaceutical compositions of embodiments 1-3 can be further formulated into medicaments containing a combination of natural ingredients with medicinal properties for the treatment of medical conditions. The natural ingredients do not cause any side effects, dependence risks, the possibility of developing drug resistance, complex interactions, long-term health risks, environmental impacts, adherence challenges, symptom masking, and ethical issues.

[0094] The effects of the pharmaceutical compositions of embodiments 1-3 are much better than the additive effects of each component used alone, which reflects the synergistic effects of each component and provides a theoretical basis for clinical application, mainly including the following aspects:

[0095] (1) Optimization of multiple insulin signaling pathways:

[0096] Gymnema sylvestre inhibits SGLT1 and GLUT2, reducing sugar absorption; Momordica charantia activates the PI3K / Akt pathway, promoting GLUT4 translocation; Curcuma longa inhibits PTP1B, enhancing insulin receptor signaling; and Melia toosendan activates the AMPK pathway, indirectly enhancing insulin sensitivity;

[0097] This multi-target regulation makes the hypoglycemic effect of the composition 35%-45% higher than the additive effect of each component used alone.

[0098] (2) Comprehensive regulation of liver metabolism:

[0099] Gymnema sylvestre inhibits hepatic glucose output; Momordica charantia promotes fatty acid oxidation; Curcuma longa inhibits lipid synthesis; and Melia toosendan promotes cholesterol conversion and excretion;

[0100] This synergistic effect makes the improvement effect of the composition on liver metabolic disorders 40% higher than that of a single component.

[0101] (3) Multi-link regulation of lipid metabolism:

[0102] The composition achieves overall improvement of blood lipids by simultaneously regulating cholesterol synthesis (M. fordii), uptake (Momordica charantia), metabolism (Curcuma longa), and excretion (Citrus aurantium), and the total cholesterol and triglyceride reduction effect is 32% higher than the cumulative effect of single components.

[0103] (4) Anti-inflammatory and antioxidant synergistic effect:

[0104] The four components form a comprehensive protection network by inhibiting different inflammatory pathways (NF-κB, COX-2, STAT3, IL-6) and enhancing various antioxidant mechanisms, and the inflammatory marker reduction efficiency is 38% higher than the cumulative effect of single components.

[0105] In addition, the pharmaceutical composition of Examples 1-3 provides significant benefits in managing diabetes, improving hyperlipidemia, and improving metabolic disorders; specifically,

[0106] Regarding the management of diabetes: fasting blood glucose is reduced by an average of 30%-35%, 2-hour postprandial blood glucose is reduced by 35%-40%, glycosylated hemoglobin (HbA1c) is reduced by 1.5-2.0 percentage points, insulin sensitivity is improved by 45%-50%, and the index of β-cell function improvement (HOMA-β) is improved by 35%-40%;

[0107] Regarding the improvement of hyperlipidemia: total cholesterol is reduced by 30%-35%, LDL cholesterol is reduced by 35%-40%, triglycerides are reduced by 35%-40%, HDL cholesterol is increased by 18%-22%, and the atherosclerosis index is improved by 40%-45%;

[0108] Regarding the improvement of metabolic indicators: body mass index (BMI) is reduced by 5-8%, waist circumference is reduced by 4-6 cm, liver function indicators (ALT, AST) are improved by 25-30%, inflammatory markers (CRP, IL-6) are reduced by 40-45%, and oxidative stress markers are reduced by 45-50%.

[0109] The language used in the specification is primarily selected for readability and instructional purposes and can not have been selected to delineate or limit the inventive subject matter. Accordingly, the scope of the present invention is intended to be limited only by the claims issued by any issuing patent of the present application based on this filing. Accordingly, embodiments of the present invention are intended to be illustrative only and not limiting of the scope of the present invention, which is set forth in the following claims.

Claims

1. A pharmaceutical composition, characterized in that, It includes: Gymnema sylvestre extract 5%-85%, Bitter melon extract 5%-85%, Turmeric extract 5%-85%, and Extracts of Citrus aurantium: 5%-85%; Wherein, % represents the mass percentage of each component in the pharmaceutical composition.

2. The pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition comprises: Gymnema sylvestre extract 15%-40%, Bitter melon extract 15%-35%, Turmeric extract 10%-30%, and Extracts from Citrus reticulata: 15%-35%.

3. The pharmaceutical composition according to claim 2, characterized in that, The pharmaceutical composition comprises: Gymnema sylvestre extract 25%-35%, Bitter melon extract 20%-30%, Turmeric extract 15%-35%, and 20%-25% of the extract from the wood orange.

4. The pharmaceutical composition according to claim 3, characterized in that, The pharmaceutical composition is any one of the following formulations: ① 30% extract of Gymnema sylvestre, 25% extract of bitter melon, 20% extract of turmeric, and 25% extract of Citrus reticulata; ② 25% extract of Gymnema sylvestre, 20% extract of bitter melon, 35% extract of turmeric, and 20% extract of Citrus aurantium; ③ 35% extract of Gymnema sylvestre, 30% extract of bitter melon, 15% extract of turmeric, and 20% extract of Citrus aurantium.

5. The pharmaceutical composition according to any one of claims 1-4, characterized in that, The pharmaceutical composition meets one or more of the following conditions: ①The extract of Gymnema sylvestre contains at least 25% gymnastic acid, where % refers to the mass percentage of gymnastic acid in the extract of Gymnema sylvestre; ②The bitter melon extract contains at least 2.5% momordicin and at least 10% bitter melon polypeptide, where % refers to the mass percentage of each active ingredient in the bitter melon extract. ③The turmeric extract contains at least 95% curcumin compounds, where % refers to the mass percentage of curcumin compounds in the turmeric extract; ④ The extract of Citrus reticulata contains at least 1.5% isopyramidal lactone and at least 3% total flavonoids, where % refers to the mass percentage of each active ingredient in the extract of Citrus reticulata. ⑤ The extraction solvents for the extracts of Gymnema sylvestre, Bitter Melon, Turmeric, and Citrus aurantium are each independently one or more of water, ethanol, methanol, a mixture of water and alcohol, supercritical fluid, and ionic liquid.

6. The pharmaceutical composition according to claim 5, characterized in that, The pharmaceutical composition meets one or more of the following conditions: ①The extract of Gymnema sylvestre contains 25% gymnemic acid, where % refers to the mass percentage of gymnemic acid in the extract of Gymnema sylvestre; ②The bitter melon extract contains 2.5% momordicin and 10% bitter melon polypeptide, where % refers to the mass percentage of each active ingredient in the bitter melon extract. ③The turmeric extract contains 95% curcumin compounds, where % refers to the mass percentage of curcumin compounds in the turmeric extract; ④ The extract of Citrus reticulata contains 1.5% isopyramidal lactone and 3% total flavonoids, where % refers to the mass percentage of each active ingredient in the extract of Citrus reticulata.

7. The pharmaceutical composition according to claim 1, characterized in that, The preparation method of the pharmaceutical composition includes the following steps in sequence: harvesting the raw materials of each of the extracts; then washing, drying, grinding, extracting and concentrating each of the raw materials; and then mixing them into a formulation. The ingredients include spoon vine leaves, bitter melon, turmeric, and tangerine peel.

8. The pharmaceutical composition according to claim 7, characterized in that, The preparation process of the pharmaceutical composition satisfies one or more of the following conditions: ① The harvest maturity standard for the leaves of Gymnema sylvestris is: leaves of Gymnema sylvestris that have grown for 3-4 months; the chlorophyll content of the leaves of Gymnema sylvestris is 20-25 mg / g; the total glycoside content of the leaves of Gymnema sylvestris is 6%-8%; % refers to the percentage of all types of glycosides in the leaves of Gymnema sylvestris by mass. After the washing and drying steps, the moisture content of the spoonwort leaves is 5%-8%, where % refers to the percentage of water by mass of the spoonwort leaves; The cleaned and dried leaves of Gymnema sylvestris are ground to obtain Gymnema sylvestris leaf powder with a particle size of 40-60 μm. The extraction method of the extract of Gymnema sylvestre includes a gradient temperature ultrasound-assisted extraction method, which includes the following steps: using a 70% ethanol aqueous solution as the first extraction solvent, the powdered leaves of Gymnema sylvestre are mixed with the first extraction solvent, the mass ratio of the first extraction solvent to the powdered leaves of Gymnema sylvestre is 8:1; extraction is carried out at 35°C for 1 hour, and then the temperature is raised to 50±2°C for 4 hours; the ultrasonic power and frequency of the ultrasound-assisted extraction method are 600W and 45kHz, respectively. ② The harvest maturity standard for bitter melon is: bitter melon with a fruit length of 15-20cm, 15-20 days after pollination; the bitter melon has a momordicin content of 0.8%-1.2%, where % refers to the percentage of momordicin by mass of bitter melon; After the washing and drying steps, the moisture content of the bitter melon is 4%-7%, where % refers to the percentage of water by mass of the bitter melon. The washed and dried bitter melon is ground to obtain bitter melon powder with a particle size of 60-80μm. The extraction method for the bitter melon extract includes a pulsed negative pressure cyclic extraction method, which includes the following steps: using a 60% ethanol aqueous solution as the second extraction solvent, the bitter melon powder is first mixed with the second extraction solvent, the mass ratio of the second extraction solvent to the bitter melon powder is 10:1; extraction is carried out at 45±2℃, the negative pressure is set to -0.08MPa, the pulse cycle is 5 minutes of negative pressure / 2 minutes of normal pressure, and the total cycle is 6 hours; ③ The harvest maturity standard for turmeric is: turmeric planted for 8-10 months with a root diameter ≥2.5cm; the curcumin content of the turmeric is ≥3.5%, where % refers to the percentage of curcumin by mass of turmeric; After the washing and drying steps, the moisture content of the turmeric is 6%-9%, where % refers to the percentage of water by mass of the turmeric. The cleaned and dried turmeric is ground to obtain turmeric powder with a particle size of 30-50 μm. The extraction method of the turmeric extract includes a microemulsion-assisted extraction method, which includes the following steps: using an 80% ethanol aqueous solution as the third extraction solvent, first mixing the turmeric powder with the third extraction solvent, wherein the mass ratio of the third extraction solvent to the turmeric powder is 6:1; and extracting at 55±2℃ for 4 hours. ④ The harvest maturity standard of the wood orange is: wood oranges with a fruit diameter of 8-10cm, 150-180 days after flowering. The content of isopurinol in the wood orange is 1.0%-1.5%, where % refers to the mass percentage of isopurinol in the wood orange. After the washing and drying steps, the moisture content of the wood orange is 5%-8%, where % refers to the percentage of water by mass of the wood orange. The cleaned and dried wood orange is ground to obtain wood orange powder with a particle size of 50-70μm; The extraction method of the extract of the citrus aurantium includes a two-phase extraction method using supercritical CO2 fluid and ethanol, which includes the following steps: using a 65% ethanol aqueous solution as the fourth extraction solvent, the citrus aurantium powder is first mixed with the fourth extraction solvent, the mass ratio of the fourth extraction solvent to the citrus aurantium powder is 7:1; the fat-soluble components are first extracted with supercritical CO2 for 2 hours, and then the water-soluble components are extracted with a 65% ethanol aqueous solution for 3.5 hours; the pressure and temperature of the supercritical CO2 are 20 MPa and 40℃, respectively.

9. The use of a pharmaceutical composition according to any one of claims 1-8 in the treatment of diabetes, hyperlipidemia and metabolic disorders.

10. A pharmaceutical preparation, characterized in that, It includes the pharmaceutical composition as described in any one of claims 1-8; the dosage form of the pharmaceutical composition is one or more of tablets, capsules, powders, granules, suspensions, emulsions, gels, creams, and lotions.