HK40065265B - Malus niedzwetzkyana dieck and prunus cerasifera ehrhart composition and use thereof in lowering blood sugar - Google Patents

Description

Combination of red-fleshed apples and cherry plums and its application in lowering blood sugar

Technical Field

This invention relates to the fields of food and pharmaceuticals, and more specifically to a composition of red-fleshed apples and cherry plums and its application in lowering blood sugar.

Background Technology

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia caused by absolute or relative insulin deficiency and/or impaired insulin utilization. According to statistics from the International Diabetes Federation (IDF) in 2017, the prevalence of diabetes mellitus among adults in China was 9.7%–11.6%, with approximately 110 million people affected, ranking first in the world.

Currently, there is no cure for diabetes. Clinically, medications used to treat diabetes mainly include sulfonylureas (such as glipizide, glimepiride, gliclazide, glibenclamide, etc.), biguanides (metformin), alpha-glucosidase inhibitors (acarbose, voglibose), insulin sensitizers (rosiglitazone, pioglitazone, etc.), insulin secretagogues (benzoic acid derivatives), DPP-4 inhibitors (saxagliptin, sitagliptin, etc.), SGLT-2 inhibitors (dapagliflozin, empagliflozin, etc.), and insulin therapy. However, a common and serious side effect of all hypoglycemic treatments is hypoglycemia. Alpha-glucosidase inhibitors, biguanides, and insulin secretagogues generally do not cause hypoglycemia when used alone, but it can still occur when used in combination with other drugs. Biguanides are particularly harmful to the gastrointestinal tract. Therefore, it is necessary to find effective and side-effect-free natural resources for the prevention and treatment of diabetes.

Red-fleshed apples (Malus neidzwetzkyana Dieck) belong to the genus Malus Mill in the family Rosaceae. Their fruit has red flesh, the color primarily caused by the accumulation of anthocyanins. Currently, there are numerous red-fleshed apple varieties worldwide, such as the Hongxun series from Xinjiang, China; Robert Crab from the United States; Ruby Sweet from Japan; and Redlove from Switzerland. The flower and leaf colors, fruit size, degree of coloring, and taste vary among different red-fleshed apple varieties. Xinjiang red-fleshed apples hold an important place in the origin of red-fleshed apples within the genus Malus Mill.

Cherry plum (Prunus cerasifera Ehrhart), commonly known as wild sour plum, belongs to the genus Prunus in the Rosaceae family. It is an extremely precious, rare, and endangered primitive wild forest fruit in the world. According to records in the "Flora of China" and verification by the National Institute of Wild Plants, wild cherry plums are only found in the western Tianshan Mountains of Xinjiang and the mountains of the Caucasus and Asia Minor, and wild resources are extremely scarce. Cherry plums have a long history of consumption in Xinjiang, my country. The Kazakh and Mongolian herders living in the Daxi Valley of the Tianshan Mountains mainly consume beef and mutton, yet the incidence of hyperlipidemia and hypertension is very low among their population. This is related to the herders' long-standing habit of picking wild cherry plums to make jam or drying the fruit for tea. Cherry plums include several varieties, mainly classified by color as black, red, purple, purplish-black, and yellow.

Red-fleshed apples and cherry plums are rich in various amino acids, vitamins, minerals, as well as functional components such as anthocyanins, polyphenols, and flavonoids, making them highly valuable for development. However, current research is still limited, mainly focusing on chemical components and antioxidants, and is still in the preliminary research stage.

Summary of the Invention

After extensive experimental research, the inventors of this application discovered that the combination of red-fleshed apples (or red-fleshed apple extracts) and cherry plums (or cherry plum extracts) has a synergistic effect in lowering blood sugar.

Therefore, in a first aspect, the present invention provides the use of the composition in the preparation of a medicine (such as traditional Chinese medicine, prepared Chinese medicine, etc.) or a health food, wherein the medicine (such as traditional Chinese medicine, prepared Chinese medicine, etc.) is used to lower blood sugar or to prevent and/or treat blood sugar disorders, and the health food is used to lower blood sugar; wherein the composition comprises:

The first component, wherein the first component is a red-fleshed apple or a red-fleshed apple extract; and

The second component is cherry plum or cherry plum extract.

In some implementations, the blood glucose disorder is selected from diabetes and diabetes-related diseases (such as type 1 diabetes, type 2 diabetes, diabetic nephropathy, etc.).

In some embodiments, the weight ratio of the first component to the second component is 1:10-10:1 (e.g., 1:5-10:1, 1:2-10:1, 1:1-10:1, 1:10-5:1, 1:5-5:1, 1:2-5:1, 1:1-5:1, 1:10-2:1, 1:5-2:1, 1:2-2:1, 1:1-2:1, 1:10-1:1, 1:5-1:1, 1 :2-1:1, 1:10-5:1, 1:10-2:1, 1:10-1:1, 1:5-10:1, 1:5-5:1, 1:5-2:1, 1:5-1:1, 1:2-10:1, 1:2-5:1, 1:2-2:1, 1:2-1:1, 1:1-10:1, 1:1-5:1, 1:1-2:1 (specifically 1:5, 1:2, 1:1, 2:1, 5:1).

In some embodiments, the red apple extract is obtained by one of the following extraction methods: immersion extraction, enzymatic ultrasonic extraction, ultra-high pressure extraction, subcritical extraction, or other extraction methods.

In some embodiments, the cherry plum extract is obtained by one of the following extraction methods: immersion extraction, enzymatic ultrasonic extraction, ultra-high pressure extraction, subcritical extraction, or other extraction methods.

In some embodiments, the composition exists in the form of fruit juice, jam, fruit powder (such as freeze-dried powder), candy (such as compressed candy), oral liquid, capsule, tablet, fruit wine, etc. In other words, the product form of the composition can be fruit juice, jam, fruit powder (such as freeze-dried powder), candy (such as compressed candy), oral liquid, capsule, tablet, fruit wine, etc. That is, the composition can be formulated into fruit juice, jam, fruit powder (such as freeze-dried powder), candy (such as compressed candy), oral liquid, capsule, tablet, fruit wine, etc.

In some implementations, the red-fleshed apple refers to the fruit of a plant in the genus Malus of the Rosaceae family, whose flesh is red.

In some implementations, the red-fleshed apples are selected from: Hongxun No. 1 (Hongxun No. 1), Hongxun No. 3 (Hongxun No. 3), Hongxun No. 6 (Hongxun No. 6), Xia Hongrou, Daihong, Red Love, Roberts Crab, Red Dream, Ruby Sweet, etc.

In some implementation schemes, the cherry plums are selected from red cherry plums, black cherry plums, purple cherry plums, purple-black cherry plums, yellow cherry plums, etc.

In a second aspect, the present invention provides a combination product comprising:

The first product is the aforementioned composition;

The second product is a medicine for the prevention and/or treatment of blood sugar disorders.

In some implementations, the blood glucose disorder is selected from diabetes and diabetes-related diseases (such as type 1 diabetes, type 2 diabetes, diabetic nephropathy, etc.).

In some embodiments, the drugs for preventing and/or treating glycemic disorders are selected from sulfonylureas (such as glipizide, glimepiride, gliclazide, glibenclamide, etc.), biguanides (metformin), alpha-glucosidase inhibitors (acarbose, voglibose), insulin sensitizers (rosiglitazone, pioglitazone, etc.), insulin secretagogues (benzoic acid derivatives), DPP-4 inhibitors (saxagliptin, sitagliptin, etc.), SGLT-2 inhibitors (dapagliflozin, empagliflozin, etc.), insulin, etc.

In some implementations, the weight ratio of the first product to the second product (such as metformin or dapagliflozin) is 20000:0.75-20000:600 (e.g., 20000:0.75, 20000:1.5, 20000:2, 20000:2.5, 20000:3, 20000:3.5, 20000:4, 20000:4.5, 20000:5, 20000:5.5, 20000:6, 20000:75, 20000:150, 20000:200, 20000:250, 20000:300). 20000:350, 20000:400, 20000:450, 20000:500, 20000:550, 20000:600; or 20000:1.5-20000:300; or 20000:150-20000:300, specifically 20000:150, 20000:200, 20000:250 or 20000:300; or 20000:1.5-20000:3, specifically 20000:1.5, 20000:2, 20000:2.5 or 20000:3).

In some implementations, when the second product is metformin, the weight ratio of the first product to the second product is 20000:75-20000:600 (e.g., 20000:75, 20000:150, 20000:200, 20000:250, 20000:300, 20000:350, 20000:400, 20000:450, 20000:500, 20000:550, 20000:600; or 20000:150-20000:300, specifically 20000:150, 20000:200, 20000:250, 20000:300).

In some implementations, when the second product is dapagliflozin, the weight ratio of the first product to the second product is 20000:0.75-20000:6 (e.g., 20000:0.75, 20000:1.5, 20000:2, 20000:2.5, 20000:3, 20000:3.5, 20000:4, 20000:4.5, 20000:5, 20000:5.5, 20000:6; or 20000:1.5-20000:3, specifically 20000:1.5, 20000:2, 20000:2.5, 20000:3).

In a third aspect, the present invention provides the use of the aforementioned combined products in the preparation of pharmaceuticals (such as traditional Chinese medicine, prepared Chinese medicine, etc.) or health foods, wherein the pharmaceuticals (such as traditional Chinese medicine, prepared Chinese medicine, etc.) are used to lower blood sugar, or to prevent and/or treat blood sugar disorders, and the health foods are used to lower blood sugar.

In a fourth aspect, the present invention provides the aforementioned compositions or combinations thereof for lowering blood sugar, or for preventing and/or treating blood sugar disorders.

In a fifth aspect, the present invention provides a method for lowering blood sugar, or for preventing and/or treating blood sugar disorders, comprising administering the aforementioned composition or the aforementioned combination product to an individual in need of such treatment.

In some implementation schemes, the aforementioned glycemic disorders are selected from diabetes and diabetes-related diseases (such as type 1 diabetes, type 2 diabetes, diabetic nephropathy, etc.).

In addition, this invention also discloses a combination product of red-fleshed apples and cherry plums for lowering blood sugar and its preparation method, including product forms such as juice, jam, freeze-dried powder, compressed candy, oral liquid, and capsules. Animal experiments have shown that this series of products has a good synergistic blood sugar lowering effect. In some embodiments, the compositions of this invention can also be used to prepare traditional Chinese medicine, prepared Chinese medicine, and other pharmaceutical products.

In another aspect, this application also provides a combination product comprising a first product and a second product in separate packaging, wherein the first product is a combination product of red-fleshed apples and cherry plums, and the second product is a hypoglycemic drug (e.g., sulfonylureas (such as glipizide, glimepiride, gliclazide, glibenclamide, etc.), biguanides (metformin), alpha-glucosidase inhibitors (acarbose, voglibose), insulin sensitizers (rosiglitazone, pioglitazone, etc.), insulin secretagogues (benzoic acid derivatives), DPP-4 inhibitors (saxagliptin, sitagliptin, etc.), SGLT-2 inhibitors (dapagliflozin, empagliflozin, etc.), insulin, etc.).

In this invention, "individual" includes humans or non-human animals. Exemplary human individuals include individuals suffering from a disease (such as the disease described herein) (referred to as patients) or normal individuals. "Non-human animals" in this invention include all vertebrates, such as non-mammals (e.g., fish, birds, amphibians, reptiles) and mammals, such as non-human primates, livestock, and/or domesticated animals (e.g., rats, sheep, dogs, cats, cows, pigs, etc.).

In this invention, "cherry plum extract" or "red apple extract" refers to a product obtained and enriched from cherry plums or red apples through physical and/or chemical extraction and separation processes to acquire one or more active ingredients from cherry plums or red apples. This product can be used as a raw material or excipient in food (e.g., ordinary food or health food) or pharmaceuticals. Exemplary extraction methods include, but are not limited to: maceration extraction, enzymatic hydrolysis and ultrasonic extraction, ultra-high pressure extraction, and subcritical extraction.

The following provides an exemplary method for preparing extracts from red-fleshed apples and cherry plums.

Extraction

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by immersion extraction (e.g., water extraction or alcohol extraction).

In some embodiments, the extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums, then blend them into a pulp to obtain fruit pulp directly, or separate the juice and pulp; in some embodiments, the juice and pulp are separated by filtering with gauze (e.g., 100-300 mesh gauze, e.g., 200 mesh gauze);

Step 2: Mix the fruit pulp or pomace with an extraction medium (e.g., water or ethanol) and extract at room temperature or under heating (e.g., 10-100°C, e.g., 50°C) conditions (e.g., 30-100 min, e.g., 60 min), then filter to obtain a fruit pulp or pomace extract; in some embodiments, the fruit pulp or pomace is mixed with the extraction medium at a weight ratio of 1:(2-10) (e.g., 1:5); in some embodiments, the ethanol is 50%-95% ethanol;

Step 3: Concentrate the pulp extract or the combined juice and pomace extract to obtain extracts of red-fleshed apples and cherry plums; in some embodiments, concentration is carried out by rotary evaporation; in some embodiments, the rotary evaporation temperature is 30-60°C, for example 50°C.

Step 4: Mix the extracted red-fleshed apple and cherry plum extracts in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1 before extraction.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by aqueous extraction, and in some embodiments, the aqueous extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and pulp; in some embodiments, the mesh size of the gauze is selected as 200 mesh.

Step 2: Mix red-fleshed apple and cherry plum pulp or pomace with water at a material-to-liquid ratio of 1:(2-10), extract at 10-100℃ for 30-100 minutes, and filter to obtain pulp or pomace extract; in some embodiments, the material-to-liquid ratio is selected as 1:5; in some embodiments, the extraction temperature is selected as 50℃; in some embodiments, the extraction time is selected as 60 minutes;

Step 3: The combined extract of red-fleshed apple and cherry plum pulp or juice and pomace is concentrated by rotary evaporation at 30-60°C to obtain a water extract of red-fleshed apple and cherry plum; in some embodiments, the rotary evaporation temperature is selected as 50°C.

Step 4: Mix the extracted red-fleshed apple and cherry plum water extracts in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1 before extraction.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by alcohol extraction, and in some embodiments, the alcohol extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and pulp; in some embodiments, the mesh size of the gauze is selected as 200 mesh.

Step 2: Mix red-fleshed apple and cherry plum pulp or pomace with 50%-95% ethanol at a material-to-liquid ratio of 1:(2-10), extract at 10-100℃ for 30-100 min, and filter to obtain pulp or pomace extract; in some embodiments, the material-to-liquid ratio is 1:5; in some embodiments, the concentration of ethanol used is 50%; in some embodiments, the extraction temperature is 50℃; in some embodiments, the extraction time is 60 min;

Step 3: The combined extract of red-fleshed apple and cherry plum pulp or juice and pomace extract is concentrated by rotary evaporation at 30-60°C, and the pulp extract is directly concentrated to obtain red-fleshed apple and cherry plum alcohol extract; in some embodiments, the rotary evaporation temperature is selected as 50°C; optionally, the extract is evaporated to remove residual ethanol.

Step 4: Mix the extracted red-fleshed apple and cherry plum alcohol extracts in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in Step 1 before extraction.

Enzymatic hydrolysis and ultrasonic extraction

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by enzymatic ultrasonic extraction (e.g., enzymatic ultrasonic water extraction or enzymatic ultrasonic alcohol extraction).

In some embodiments, the enzymatic hydrolysis and ultrasonic extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums, then blend them into a pulp to obtain fruit pulp directly, or separate the juice and pulp; in some embodiments, the juice and pulp are separated by filtering with gauze (e.g., 100-300 mesh gauze, e.g., 200 mesh gauze);

Step 2: Mix the fruit pulp or pomace with the extraction medium (e.g., water or ethanol) and cellulase, and extract under heating conditions (e.g., 30-50°C, e.g., 45°C) for 30-100 min, e.g., 60 min, followed by sonication under ultrasonic conditions (e.g., 100-500W ultrasonic power) for 20-60 min, e.g., 30 min, and filter to obtain the fruit pulp or pomace extract; in some embodiments, the amount of cellulase added (based on the weight of the pomace or fruit pulp) is 0.2%-1% (e.g., 0.5%); in some embodiments, the fruit pulp or pomace is mixed with the extraction medium at a weight ratio of 1:(2-10) (e.g., 1:5); in some embodiments, the ethanol is 50%-95% ethanol;

Step 3: Concentrate the combined extract of red-fleshed apple and cherry plum pulp or juice and pomace extract to obtain enzymatically hydrolyzed ultrasonic extracts of red-fleshed apple and cherry plum; in some embodiments, concentration is carried out by rotary evaporation; in some embodiments, the rotary evaporation temperature is 30-60°C, for example 50°C.

Step 4: Mix the extracted red-fleshed apple and cherry plum enzymatic hydrolysis ultrasonic extracts in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then extract them.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by enzymatic hydrolysis and ultrasonic water extraction. In some embodiments, the enzymatic hydrolysis and ultrasonic water extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and pulp; in some embodiments, the mesh size of the gauze is selected as 200 mesh.

Step 2: Mix red-fleshed apple and cherry plum pulp or pomace with water at a material-to-liquid ratio of 1:(2-10), add 0.2%-1% (based on the weight of the pulp or pomace) of cellulase, extract in a water bath at 30-50℃ for 30-100 min, and sonicate at 100-500W for 20-60 min. Filter to obtain the pulp or pomace extract. In some embodiments, the material-to-liquid ratio is 1:5; in some embodiments, the amount of cellulase added is 0.5%; in some embodiments, the water bath temperature is 45℃; in some embodiments, the extraction time is 60 min; in some embodiments, the ultrasonic power is 500W; in some embodiments, the ultrasonic time is 30 min.

Step 3: The combined liquid of red-fleshed apple and cherry plum pulp or juice and pomace extract is concentrated by rotary evaporation at 30-60℃ to obtain the enzymatically hydrolyzed ultrasonically extracted aqueous extract of red-fleshed apple and cherry plum; in some embodiments, the rotary evaporation temperature is selected as 50℃.

Step 4: Mix the extracted red-fleshed apple and cherry plum enzymatic hydrolysis ultrasonic water extracts in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then extract them.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by enzymatic hydrolysis and ultrasonic alcohol extraction. In some embodiments, the enzymatic hydrolysis and ultrasonic alcohol extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and pulp; in some embodiments, the mesh size of the gauze is selected as 200 mesh.

Step 2: Mix red-fleshed apple and cherry plum pulp or pomace with 50%-95% ethanol at a material-to-liquid ratio of 1:(2-10), add 0.2%-1% (based on the weight of the pomace or pulp) of cellulase, extract in a water bath at 30-50℃ for 30-100 min, sonicate at 100-500W for 20-60 min, and filter to obtain the pulp or pomace extract; in some embodiments, the material-to-liquid ratio is selected as 1:5; in some embodiments, the concentration of ethanol used is 50%; in some embodiments, the amount of cellulase added is 0.5%; in some embodiments, the water bath temperature is 45℃; in some embodiments, the extraction time is selected as 60 min; in some embodiments, the ultrasonic power is 500W; in some embodiments, the ultrasonic time is 30 min;

Step 3: The combined extract of red-fleshed apple and cherry plum pulp or juice and pomace is concentrated by rotary evaporation at 30-60°C to obtain an enzymatically hydrolyzed ultrasonically extracted alcoholic extract of red-fleshed apple and cherry plum; in some embodiments, the rotary evaporation temperature is selected as 50°C; optionally, the extract is evaporated to remove residual ethanol.

Step 4: Mix the extracted red-fleshed apple and cherry plum enzymatic hydrolysis ultrasonic alcohol extracts in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then extract them.

Ultra-high pressure extraction

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by ultra-high pressure extraction (e.g., ultra-high pressure water extraction or ultra-high pressure alcohol extraction). As used herein, "ultra-high pressure" refers to a pressure exceeding 100 MPa (equivalent to 1000 atmospheres).

In some embodiments, the ultra-high pressure extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums, then blend them into a pulp to obtain fruit pulp directly, or separate the juice and pulp; in some embodiments, the juice and pulp are separated by filtering with gauze (e.g., 100-300 mesh gauze, e.g., 200 mesh gauze);

Step 2: Mix the fruit pulp or pomace with an extraction medium (e.g., water or ethanol), treat under ultra-high pressure (e.g., 200-600 MPa, e.g., 400 MPa) for 3-10 min, e.g., 5 min), and filter to obtain a fruit pulp or pomace extract; in some embodiments, the fruit pulp or pomace is mixed with the extraction medium at a weight ratio of 1:(2-10) (e.g., 1:5); in some embodiments, the ethanol is 50%-95% ethanol;

Step 3: Concentrate the combined liquid of red-fleshed apple and cherry plum pulp or juice with pomace extract to obtain ultra-high pressure extracts of red-fleshed apple and cherry plum; in some embodiments, concentration is carried out by rotary evaporation; in some embodiments, the rotary evaporation temperature is 30-60°C, for example 50°C;

Step 4: Mix the extracted red-fleshed apple and cherry plum ultra-high pressure extracts in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1 before extraction.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by ultra-high pressure water extraction, and in some embodiments, the ultra-high pressure water extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and pulp; in some embodiments, the mesh size of the gauze is selected as 200 mesh.

Step 2: Mix red-fleshed apple and cherry plum pulp or pomace with water at a material-to-liquid ratio of 1:(2-10), treat under ultra-high pressure at 200-600MPa for 3-10 minutes, and filter to obtain pulp or pomace extract; in some embodiments, the material-to-liquid ratio is selected as 1:5; in some embodiments, the ultra-high pressure is 400MPa; in some embodiments, the ultra-high pressure treatment time is selected as 5 minutes;

Step 3: The combined extract of red-fleshed apple and cherry plum pulp or juice and pomace is concentrated by rotary evaporation at 30-60℃ to obtain ultra-high pressure water extract of red-fleshed apple and cherry plum; in some embodiments, the rotary evaporation temperature is selected as 50℃.

Step 4: Mix the extracted red-fleshed apple and cherry plum ultra-high pressure water extracts in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1 before extraction.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by ultra-high pressure alcohol extraction, and in some embodiments, the ultra-high pressure alcohol extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and pulp; in some embodiments, the mesh size of the gauze is selected as 200 mesh.

Step 2: Red-fleshed apple and cherry plum pulp or pomace are mixed with 50%-95% ethanol at a material-to-liquid ratio of 1:(2-10), and treated under ultra-high pressure at 200-600 MPa for 3-10 minutes. The mixture is then filtered to obtain a pulp or pomace extract. In some embodiments, the material-to-liquid ratio is 1:5; in some embodiments, the ultra-high pressure is 400 MPa; in some embodiments, the ultra-high pressure treatment time is 5 minutes; in some embodiments, the ethanol is 50% ethanol.

Step 3: The combined extract of red-fleshed apple and cherry plum pulp or juice and pomace is concentrated by rotary evaporation at 30-60°C to obtain an ultra-high pressure extract of red-fleshed apple and cherry plum; in some embodiments, the rotary evaporation temperature is selected as 50°C; optionally, the extract is evaporated to remove residual ethanol.

Step 4: Mix the extracted red-fleshed apple and cherry plum ultra-high pressure alcohol extracts in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1 before extraction.

Subcritical extraction (also known as "subcritical extraction")

In some embodiments, red-fleshed apple and cherry plum extracts are obtained by subcritical extraction (e.g., subcritical water extraction or subcritical alcohol extraction).

In some implementations, the subcritical extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums, then blend them into a pulp to obtain fruit pulp directly, or separate the juice and pulp; in some embodiments, the juice and pulp are separated by filtering with gauze (e.g., 100-300 mesh gauze, e.g., 200 mesh gauze);

Step 2: Mix the fruit pulp or pomace with an extraction medium (e.g., water or ethanol) and perform subcritical extraction (e.g., 10-50 min, e.g., 30 min), then filter to obtain the fruit pulp or pomace extract; in some embodiments, the fruit pulp or pomace is mixed with the extraction medium at a weight ratio of 1:(2-10) (e.g., 1:5); in some embodiments, the ethanol is 50%-95% ethanol; in some embodiments, the subcritical extraction temperature is 100-150°C (e.g., 110°C);

Step 3: Concentrate the combined liquid of fruit pulp or juice and pomace extract to obtain subcritical extracts of red-fleshed apples and cherry plums; in some embodiments, concentration is carried out by rotary evaporation; in some embodiments, the rotary evaporation temperature is 30-60°C, for example 50°C.

Step 4: Mix the extracted subcritical extracts of red-fleshed apples and cherry plums in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in Step 1 before extraction.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by subcritical water extraction, and in some embodiments, the subcritical water extraction includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, separating the juice and pulp; in some embodiments, the mesh number of the gauze is 200 mesh.

Step 2: Mix red-fleshed apple and cherry plum pulp or pomace with water at a material-to-liquid ratio of 1:(2-10), perform subcritical extraction for 10-50 min at a processing temperature of 100-150℃, and filter to obtain pulp or pomace extract; in some embodiments, the material-to-liquid ratio is selected as 1:5; in some embodiments, the processing temperature is 110℃; in some embodiments, the processing time is 30 min;

Step 3: The combined extract of red-fleshed apple and cherry plum pulp or juice and pomace is concentrated by rotary evaporation at 30-60℃ to obtain subcritical aqueous extracts of red-fleshed apple and cherry plum; in some embodiments, the rotary evaporation temperature is selected as 50℃.

Step 4: Mix the extracted subcritical water extracts of red-fleshed apples and cherry plums in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in Step 1 before extraction.

In some embodiments, the red-fleshed apple and cherry plum extracts of the present invention are obtained by subcritical alcohol extraction, which in some embodiments includes the following steps:

Step 1: Remove the seeds or pits from the red-fleshed apples and cherry plums respectively, then blend them into a pulp to obtain fruit pulp directly, or filter the juice through 100-300 mesh gauze to obtain red-fleshed apple and cherry plum juice, separating the juice and pulp; in some embodiments, the mesh number of the gauze is 200 mesh.

Step 2: Mix red-fleshed apple and cherry plum pulp or pomace with 50%-95% ethanol at a material-to-liquid ratio of 1:(2-10), perform subcritical extraction for 10-50 min at a processing temperature of 100-150℃, and filter to obtain pulp or pomace extract; in some embodiments, the material-to-liquid ratio is selected as 1:5; in some embodiments, the processing temperature is 110℃; in some embodiments, the processing time is 30 min;

Step 3: The combined extract of red-fleshed apple and cherry plum pulp or juice and pomace is concentrated by rotary evaporation at 30-60°C to obtain a subcritical alcohol extract of red-fleshed apple and cherry plum; in some embodiments, the rotary evaporation temperature is selected as 50°C; optionally, the extract is evaporated to remove residual ethanol.

Step 4: Mix the extracted subcritical alcohol extracts of red-fleshed apples and cherry plums in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1 before extraction.

As previously stated, the product forms of the compositions of the present invention can be fruit juice, jam, fruit powder (such as freeze-dried powder), candy (such as compressed candy), oral liquid, capsule, tablet, or fruit wine. Additionally, the product forms of the compositions of the present invention can be pharmaceuticals or health foods. In some embodiments, in product forms such as fruit juice, jam, fruit powder (such as freeze-dried powder), candy (such as compressed candy), oral liquid, capsule, tablet, and fruit wine, the compositions of the present invention can be used as the main raw material, for example, accounting for more than 30 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt%, 90 wt%, or 100 wt% of the total raw materials; optionally, the product may also contain other ingredients such as water, sweeteners, or other types of fruits or their extracts.

The following provides exemplary methods for preparing red-fleshed apple and cherry plum products (e.g., juice, jam, freeze-dried powder, compressed candy, oral liquid, capsule).

juice

In some implementations, red apple and cherry plum juice can be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Filter the slurry (e.g., using 100-300 mesh gauze) to obtain a cloudy juice of red-fleshed apple and cherry plum; in some embodiments, the gauze has a mesh size of 200.

Step 3: Mix red apple and cherry plum juice in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix red apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then pulp them to prepare juice.

In some implementations, red apple and cherry plum juice can also be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Filter the slurry (e.g., using 100-300 mesh gauze), add pectinase for enzymatic hydrolysis and filtration; to obtain clear juice of red-fleshed apple and cherry plum; in some embodiments, the gauze has a mesh size of 200.

Step 3: Mix red apple and cherry plum juice in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix red apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then pulp them to prepare juice.

jam

In some implementations, red apple and cherry plum jam can be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Boil and heat the fruit pulp to concentrate it into red apple and cherry plum jam;

Step 3: Mix red-fleshed apple and cherry plum jam in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then pulp them to prepare jam.

freeze-dried powder

In some implementations, freeze-dried powders of red-fleshed apples and cherry plums can be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red-fleshed apples and cherry plums, then blend them into a puree.

Step 2: Freeze-dry the fruit pulp to produce freeze-dried fruit pulp powder;

Step 3: Mix red-fleshed apple and cherry plum freeze-dried powders in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then pulp them to prepare freeze-dried powder.

In some implementations, freeze-dried powders of red-fleshed apples and cherry plums can also be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Filter the slurry (e.g., using 100-300 mesh gauze) to obtain red-fleshed apple and cherry plum juice; in some embodiments, the gauze has a mesh size of 200.

Step 3: Freeze-dry the fruit juice to make freeze-dried fruit juice powder;

Step 4: Mix the freeze-dried powders of red-fleshed apples and cherry plums in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the raw materials of red-fleshed apples and cherry plums in the aforementioned different proportions in step 1, and then pulp them to prepare freeze-dried powder.

Compressed candy

In some implementations, red apple and cherry plum compressed candies can be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Freeze-dry the fruit pulp to produce freeze-dried fruit pulp powder;

Step 3: Compress the freeze-dried fruit pulp powder and excipients into tablets to make compressed candy;

Step 4: Mix red apple and cherry plum compressed candy in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix red apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then beat them to prepare compressed candy.

In some implementations, the red apple and cherry plum compressed candy can also be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Filter the slurry (e.g., using 100-300 mesh gauze) to obtain red apple juice; in some embodiments, the gauze has a mesh size of 200.

Step 3: Freeze-dry the fruit juice to make freeze-dried fruit juice powder;

Step 4: Compress the freeze-dried fruit juice powder and excipients into tablets to make compressed candy.

Step 5: Mix red apple and cherry plum compressed candy in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix red apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then beat them to prepare compressed candy.

oral liquid

In some implementations, the red-fleshed apple and cherry plum oral liquid can be obtained by a method comprising the following steps:

Step 1: Prepare extracts of red-fleshed apple and cherry plum in different proportions (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) (e.g., by maceration, enzymatic hydrolysis, ultrasonic extraction, ultra-high pressure extraction or subcritical extraction, with the same steps as above);

Step 2: Sterilize the extracts of red-fleshed apples and cherry plums to obtain red-fleshed apple oral liquid.

In some implementations, the red apple and cherry plum oral liquid can also be obtained by a method comprising the following steps:

Step 1: Prepare extracts of red-fleshed apple and cherry plum in different proportions (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) (e.g., by maceration, enzymatic hydrolysis, ultrasonic extraction, ultra-high pressure extraction or subcritical extraction, with the same steps as above);

Step 2: Add pectinase for enzymatic hydrolysis and filtration to prepare a clear juice extract composition;

Step 3: Sterilize the juice extracts of red-fleshed apples and cherry plums to obtain red-fleshed apple oral liquid.

capsule

In some implementations, red-fleshed apple and cherry plum capsules can be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Freeze-dry the fruit pulp to produce freeze-dried fruit pulp powder;

Step 3: Mix red-fleshed apple and cherry plum freeze-dried powders in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix red-fleshed apple and cherry plum raw materials in the aforementioned different proportions in step 1, and then pulp them to prepare freeze-dried powder;

Step 4: Fill the freeze-dried fruit pulp powder into capsule shells to make capsules.

In some implementations, red-fleshed apple and cherry plum capsules can also be obtained by a method comprising the following steps:

Step 1: Remove the pits or cores from the red apples and cherry plums, then blend them into a puree;

Step 2: Filter the slurry (e.g., using 100-300 mesh gauze) to obtain red-fleshed apple and cherry plum juice; in some embodiments, the gauze has a mesh size of 200.

Step 3: Freeze-dry the fruit juice to make freeze-dried fruit juice powder;

Step 4: Mix the freeze-dried powders of red-fleshed apples and cherry plums in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or mix the raw materials of red-fleshed apples and cherry plums in the aforementioned different proportions in step 1, and then pulp them to prepare freeze-dried powder.

Step 5: Fill the freeze-dried fruit juice powder into capsule shells to make capsules.

Beneficial effects

This invention utilizes natural red-fleshed apples and cherry plums. The resulting combination product exhibits excellent hypoglycemic effects, with the combined effect superior to using either red-fleshed apple or cherry plum alone, demonstrating a synergistic effect. Furthermore, the combination of this composition with a drug is more effective than either the composition or the drug alone.

Detailed Implementation

The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are only for illustrating the present invention and should not be regarded as limiting the scope of the present invention.

Example 1:

The red-fleshed apples and cherry plums mentioned in this embodiment refer to fresh red-fleshed apples and cherry plums.

Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are harvested one month before maturity until fully ripe. Harvesting is preferred on sunny days. Rotten or poorly colored fruit is selected and removed, and then refrigerated after harvesting. The resulting red-fleshed apples and cherry plums are combined in different ratios (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1), and the fresh fruit can be eaten directly.

Example 2:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the juice of red-fleshed apples and cherry plums.

After harvesting, red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are seeded or pitted and then pulped. The juice is filtered through 200-mesh gauze to obtain cloudy juice of red-fleshed apples and cherry plums. The cloudy juice of red-fleshed apples and cherry plums is mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or the raw materials of red-fleshed apples and cherry plums are first mixed in the aforementioned different proportions and then pulped to prepare juice.

Example 3:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the juice of red-fleshed apples and cherry plums.

After harvesting, red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are seeded or pitted and then pulped. The juice is filtered through 200-mesh gauze to obtain cloudy juice of red-fleshed apples and cherry plums. Pectinase is added for enzymatic hydrolysis, and the filtered juice is clear. The clear juice of red-fleshed apples and cherry plums is mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composite, or the raw materials of red-fleshed apples and cherry plums are first mixed in the aforementioned different proportions and then pulped to prepare the juice.

Example 4:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to red-fleshed apple and cherry plum jam.

After removing the seeds or pits from red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit), the mixture is pureed and then boiled to make a thick jam. The red-fleshed apple and cherry plum jams are then mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composite, or the red-fleshed apple and cherry plum raw materials are first mixed in the aforementioned different proportions and then pureed to prepare the jam.

Example 5:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to freeze-dried red-fleshed apple and cherry plum powder.

Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are pitted or de-cored, then pulped and freeze-dried to produce freeze-dried fruit pulp powder. The freeze-dried red-fleshed apple and cherry plum powders are mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composite, or the raw materials are first mixed in the aforementioned different proportions, and then pulped to prepare freeze-dried powder.

Example 6:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to compressed candies made from red-fleshed apples and cherry plums.

Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are pitted or de-seeded, then pulped and freeze-dried to produce freeze-dried fruit pulp powder. The freeze-dried fruit pulp powder and excipients are then compressed into tablets to produce compressed candies. Red-fleshed apple and cherry plum tablets can be mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, or the raw materials of red-fleshed apples and cherry plums can be mixed in the aforementioned different proportions first, and then pulped to prepare compressed candies.

Example 7:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to oral liquids extracted from red-fleshed apples and cherry plums by water.

(1) Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are pulped after removing the seeds or pits to obtain red-fleshed apple and cherry plum pulp.

(2) Add water to the red-fleshed apple and cherry plum pulp at a ratio of 1:5, extract by water soaking at 50°C for 60 minutes, and filter to obtain pulp extract.

(3) The extract was concentrated by rotary evaporation at 50°C to obtain water extracts of red apple and cherry plum.

(4) The extracted red apple and cherry plum extracts were mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition.

(5) The extract of red apple and cherry plum was sterilized to prepare an oral liquid.

Example 8:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to oral liquids extracted from red-fleshed apples (Red Love) and cherry plums (Red Fruit). The preparation steps are the same as in Example 7.

Example 9:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the oral liquid extracted from red-fleshed apple (Hongxun No. 1) and cherry plum (black fruit).

The fruit pulp was processed according to steps (1)-(5) of Example 7, wherein 50% ethanol was added at a material-to-liquid ratio of 1:5. The ethanol extract was then subjected to ethanol evaporation treatment.

Example 10:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the enzymatically hydrolyzed ultrasonic water extract oral liquid of red-fleshed apple and cherry plum.

(1) Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are pulped after removing the seeds or pits to obtain red-fleshed apple and cherry plum pulp.

(2) Add water to red apple and cherry plum pulp at a ratio of 1:5, add 0.5% (based on the weight of pulp) of cellulase, extract in a 45℃ water bath for 60 min, sonicate at 500W for 30 min, and filter to obtain pulp extract.

(3) The extract was concentrated by rotary evaporation at 50°C to obtain enzymatically hydrolyzed ultrasonic water extracts of red-fleshed apples and cherry plums.

(4) The extracted red apple and cherry plum extracts were mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition.

(5) The extract of red apple and cherry plum was sterilized to prepare an oral liquid.

Example 11:

The red-fleshed apple and cherry plum products described in this embodiment refer to the enzymatically hydrolyzed ultrasonic water extract oral liquid of red-fleshed apple (Hongxun No. 3) and cherry plum (red fruit). The preparation steps are the same as in Example 10.

Example 12:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the enzymatically hydrolyzed ultrasonic alcohol extract oral liquid of red-fleshed apple (Hongxun No. 1) and cherry plum (black fruit).

The treatment was carried out according to steps (1)-(5) of Example 10, wherein the fruit pulp was added at a ratio of 1:5 with 50% alcohol. The alcohol extract was subjected to ethanol evaporation treatment.

Example 13:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the oral liquid extracted from red-fleshed apples and cherry plums using ultra-high pressure water extraction.

(1) Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are pulped after removing the seeds or pits to obtain red-fleshed apple and cherry plum pulp.

(2) Add water to the red apple and cherry plum pulp at a ratio of 1:5, treat under ultra-high pressure of 400 MPa for 5 minutes, and filter to obtain pulp extract.

(3) The extract was concentrated by rotary evaporation at 50°C to obtain ultra-high pressure water extracts of red apple and cherry plum.

(4) The extracted red apple and cherry plum extracts were mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition.

(5) The extract of red apple and cherry plum was sterilized to prepare an oral liquid.

Example 14:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the oral liquid extracted from red-fleshed apple (Hongxun No. 6) and cherry plum (red fruit) under ultra-high pressure water extraction. The preparation steps are the same as in Example 13.

Example 15:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to the ultra-high pressure alcohol extract oral liquid of red-fleshed apple (Hongxun No. 1) and cherry plum (black fruit).

The treatment was carried out according to steps (1)-(5) of Example 13, wherein the fruit pulp was added at a ratio of 1:5 with 50% alcohol. The alcohol extract was subjected to ethanol evaporation treatment.

Example 16:

The red-fleshed apple and cherry plum products mentioned in this embodiment refer to subcritical water extract oral solutions of red-fleshed apples and cherry plums.

(1) Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are pulped after removing the seeds or pits to obtain red-fleshed apple and cherry plum pulp.

(2) Add water to the pulp of red apples and cherry plums at a ratio of 1:5, perform subcritical extraction for 30 minutes at a temperature of 110℃, and filter to obtain pulp extract.

(3) The extract was concentrated by rotary evaporation at 50°C to obtain subcritical water extracts of red apple and cherry plum.

(4) The extracted red apple and cherry plum extracts were mixed in different proportions (by weight) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition.

(5) The extract of red apple and cherry plum was sterilized to prepare an oral liquid.

Evaluation of the hypoglycemic effect of the product in the example:

Experiment Example 1: Evaluation of the blood glucose-lowering effect of zebrafish

(1) Test methods

Zebrafish juveniles at 5 days post-fertilization (dpf) were selected and divided into a model group, a control group, a positive control group (metformin), and a sample group. The model group, positive control group, and sample group were treated with glucose solution and fed a high-fat diet; the control group was cultured in a controlled aquaculture system and fed a high-fat diet. The juveniles were fed twice daily. The positive control group received metformin, and the sample group received the test sample. At 9 dpf, the juveniles were collected, ground, and water was added. The glucose content in the total tissue fluid was measured using a glucometer.

Glucose inhibition rate (%) = (Glucose in the model group - Glucose in the drug group) / Glucose in the model group × 100

(2) Test Results

The experimental results are shown in Table 1 below. In Table 1, the samples of the red-fleshed apple group and the cherry plum group are the red-fleshed apple enzymatic hydrolysis ultrasonic water extract and cherry plum enzymatic hydrolysis ultrasonic water extract prepared in step (3) of Example 10, respectively. The samples of the red-fleshed apple and cherry plum combination group are the combinations prepared in each weight ratio in step (4) of Example 10. In addition, the corresponding administration concentrations for each group are shown with a single underline, where: 1 mg/mL or 0.5 mg/mL indicates the concentration of the positive drug dispersed in water; 0.01% indicates the concentration of the red-fleshed apple enzymatic hydrolysis ultrasonic water extract, or the cherry plum enzymatic hydrolysis ultrasonic water extract, or the combination composed of red-fleshed apple enzymatic hydrolysis ultrasonic water extract and cherry plum enzymatic hydrolysis ultrasonic water extract in different weight ratios dispersed in water.

Subsequently, referring to CN104127427B "An Anticancer Synergistic Composition" and the literature "Synergistic Effect of Combined Use of Curcumin and Doxorubicin in Antitumor Treatment," the interaction coefficient q was calculated as q = E(A+B)/(EA+(1-EA)×EB). Where E(A+B) is the inhibition rate of the two drugs used together, and EA and EB are the inhibition rates of the two drugs used alone. q of 0.85-1.15 indicates additive effects, q > 1.15 indicates enhanced effects and synergistic effects, and q < 0.85 indicates antagonistic effects between the two drugs. The calculation results are shown in Table 1 below.

Table 1. Blood glucose lowering effect of red-fleshed apple and cherry plum combination (Example 10) zebrafish

All values were statistically significant compared to the model group; *p < 0.05, **p < 0.01, ***p < 0.001

As shown in Table 1 above, the glycemic inhibition rate of the combination of red apple and cherry plum (10:1-1:10) is higher than that of the combination when used alone, and the calculated q values are all greater than 1.15, indicating that it has a synergistic effect.

Furthermore, the combination of red-fleshed apples and cherry plums exhibits an additive effect when used in combination with a positive control drug (0.85 < q < 1.15). The hypoglycemic effect of the combination with the positive control drug is superior to that of its single use. Combining it with a lower dose of the positive control drug significantly enhances the effect.

Experiment Example 2: Evaluation of the hypoglycemic effect in mice

(1) Test methods

Healthy db/db mice were used and divided into a positive control group (metformin or dapagliflozin), a model group, and a sample group; a normal control group consisted of C57 wild-type mice with a BKS background; each group consisted of 20 mice. After acclimatization, the model group was given distilled water (0.5 mL/mouse), the positive control group was given metformin or dapagliflozin, and the sample group was given the sample (0.5 mL/mouse). The experiment lasted for 14 days. Blood was collected from the tail tip, and the glucose content in the mice's blood was measured using a glucometer.

Glucose inhibition rate (%) = (Glucose level in model group - Glucose level in drug group) / Glucose level in model group × 100

(2) Test Results

The experimental results are shown in Table 2 below. In Table 2, the samples of the red-fleshed apple group and the cherry plum group are the enzymatic hydrolysis ultrasonic water extract of red-fleshed apple and the enzymatic hydrolysis ultrasonic water extract of cherry plum prepared in step (3) of Example 10, respectively. The samples of the red-fleshed apple and cherry plum combination group are the combinations of each weight ratio prepared in step (4) of Example 10. In addition, the corresponding dosage of each group is shown with a single underline.

Subsequently, referring to CN104127427B "An Anticancer Synergistic Composition" and the literature "Synergistic Effect of Combined Use of Curcumin and Doxorubicin in Antitumor Treatment," the interaction coefficient q was calculated as q = E(A+B)/(EA+(1-EA)×EB). Where E(A+B) is the inhibition rate of the two drugs used together, and EA and EB are the inhibition rates of the two drugs used alone. q = 0.85-1.15 indicates additive effects, q > 1.15 indicates enhanced effects and synergistic effects, and q < 0.85 indicates antagonistic effects between the two drugs. The calculation results are shown in Table 2 below.

Table 2. Hypoglycemic effect of red-fleshed apple and cherry plum combination (Example 10) in mice

All values were statistically significant compared to the model group; *p < 0.05, **p < 0.01, ***p < 0.001

As shown in Table 1 above, the glycemic inhibition rate of the red-fleshed apple and cherry plum combination (10:1-1:10) was higher than that of the combination when used alone, and the calculated q values were all greater than 1.15, indicating a synergistic effect. In addition, the red-fleshed apple and cherry plum combination had an additive effect when used in combination with positive control drugs (0.85 < q < 1.15).

The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Any modifications or equivalent substitutions to the technical solutions of the present invention that do not depart from the spirit and scope of the technical solutions of the present invention should be covered within the protection scope of the present invention.

Claims (15)

1. Use of the composition in the preparation of a pharmaceutical or health food, wherein the pharmaceutical is used to lower blood sugar or to prevent and/or treat blood sugar disorders, and the health food is used as an adjunct to lower blood sugar; wherein the composition comprises the following first and second components as active ingredients: The first component is a red-fleshed apple extract; the variety of the red-fleshed apple is Hongxun No. 1. The second component is cherry plum black fruit extract; The weight ratio of the first component to the second component is 1:10, 1:5, 1:2, 1:1, 2:1, 5:1 or 10:1; The composition is obtained by a method comprising the following steps: (1) After removing the seeds or pits from red-fleshed apples and cherry plums, they are mashed to obtain red-fleshed apple and cherry plum pulp; (2) Add water to red-fleshed apple and cherry plum pulp at a ratio of 1:5, add 0.5% cellulase by weight of pulp, extract in a 45℃ water bath for 60 min, sonicate at 500W for 30 min, and filter to obtain pulp extract. (3) The extract was concentrated by rotary evaporation at 50°C to obtain enzymatically hydrolyzed ultrasonic water extracts of red-fleshed apples and cherry plums. (4) The extracted red apple and cherry plum extracts were mixed in a weight ratio of 1:10, 1:5, 1:2, 1:1, 2:1, 5:1 or 10:1 to prepare a composition. 2. The use according to claim 1, wherein the drug is a traditional Chinese medicine or a prepared traditional Chinese medicine. 3. The use of claim 1, wherein the blood glucose disorder is selected from diabetes and diabetes-related diseases. 4. The use of claim 1, wherein the blood glucose disorder is selected from type I diabetes, type II diabetes, and diabetic nephropathy. 5. The use of claim 1, wherein the composition is in the form of an oral liquid, capsule or tablet. 6. Combination products, including: The first product is the composition defined in any one of claims 1-5; The second product is a medicine for the prevention and/or treatment of blood sugar disorders. 7. The combination product of claim 6, wherein the glycemic disorder is selected from diabetes and diabetes-related diseases. 8. The combination product of claim 6, wherein the glycemic disease is selected from, for example, type 1 diabetes, type 2 diabetes, and diabetic nephropathy. 9. The combination product of claim 6, wherein the medicament for preventing and/or treating glycemic disorders is selected from sulfonylureas, biguanides, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, DPP-4 inhibitors, SGLT-2 inhibitors, and insulin. 10. The combination product of claim 6, wherein the medicine for preventing and/or treating glycemic disorders is selected from glipizide, glimepiride, gliclazide, glibenclamide, metformin, acarbose, voglibose, rosiglitazone, pioglitazone, benzoic acid derivatives, saxagliptin, sitagliptin, dapagliflozin, and empagliflozin. 11. The combined product of claim 6, wherein the weight ratio of the first product to the second product is 20000:0.75-20000:600. 12. Use of the combination product according to any one of claims 6-11 in the preparation of a medicament for lowering blood glucose or for the prevention and/or treatment of blood glucose disorders. 13. The use of claim 12, wherein the drug is a traditional Chinese medicine preparation. 14. The use of claim 12, wherein the blood glucose disorder is selected from diabetes and diabetes-related diseases. 15. The use of claim 12, wherein the blood glucose disorder is selected from type I diabetes, type II diabetes, and diabetic nephropathy.