WO2022111570A1 - 红肉苹果和樱桃李组合物及其在降血糖方面的应用 - Google Patents

红肉苹果和樱桃李组合物及其在降血糖方面的应用 Download PDF

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Publication number
WO2022111570A1
WO2022111570A1 PCT/CN2021/133058 CN2021133058W WO2022111570A1 WO 2022111570 A1 WO2022111570 A1 WO 2022111570A1 CN 2021133058 W CN2021133058 W CN 2021133058W WO 2022111570 A1 WO2022111570 A1 WO 2022111570A1
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Prior art keywords
red
cherry plum
apple
fruit
fleshed
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PCT/CN2021/133058
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English (en)
French (fr)
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沈妍
张正方
韩铨
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浙江养生堂天然药物研究所有限公司
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Publication of WO2022111570A1 publication Critical patent/WO2022111570A1/zh

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/02—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation containing fruit or vegetable juices
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A23G3/364—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing microorganisms or enzymes; containing paramedical or dietetical agents, e.g. vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23G—COCOA; COCOA PRODUCTS, e.g. CHOCOLATE; SUBSTITUTES FOR COCOA OR COCOA PRODUCTS; CONFECTIONERY; CHEWING GUM; ICE-CREAM; PREPARATION THEREOF
    • A23G3/00—Sweetmeats; Confectionery; Marzipan; Coated or filled products
    • A23G3/34—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof
    • A23G3/36—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds
    • A23G3/48—Sweetmeats, confectionery or marzipan; Processes for the preparation thereof characterised by the composition containing organic or inorganic compounds containing plants or parts thereof, e.g. fruits, seeds, extracts
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L19/00—Products from fruits or vegetables; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L19/00—Products from fruits or vegetables; Preparation or treatment thereof
    • A23L19/01—Instant products; Powders; Flakes; Granules
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/70—Clarifying or fining of non-alcoholic beverages; Removing unwanted matter
    • A23L2/84—Clarifying or fining of non-alcoholic beverages; Removing unwanted matter using microorganisms or biological material, e.g. enzymes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L21/00—Marmalades, jams, jellies or the like; Products from apiculture; Preparation or treatment thereof
    • A23L21/10—Marmalades; Jams; Jellies; Other similar fruit or vegetable compositions; Simulated fruit products
    • A23L21/12—Marmalades; Jams; Jellies; Other similar fruit or vegetable compositions; Simulated fruit products derived from fruit or vegetable solids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A23L33/25—Synthetic polymers, e.g. vinylic or acrylic polymers
    • A23L33/26—Polyol polyesters, e.g. sucrose polyesters; Synthetic sugar polymers, e.g. polydextrose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
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    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • cherry plums It is related to the habit of picking wild cherry plums for a long time to make jam or drying the fruit to make tea.
  • cherry plums There are many varieties of cherry plums, mainly black fruit, red fruit, purple fruit, purple black fruit, yellow fruit and so on according to the color.
  • Red-fleshed apples and cherry plums are rich in a variety of amino acids, vitamins, minerals, and functional components such as anthocyanins, polyphenols, and flavonoids, and have high development value.
  • the current research is still relatively limited, mainly focusing on chemical components and antioxidants, and it is still in the preliminary research stage.
  • red-fleshed apple or red-flesh apple extract
  • cherry plum or cherry plum extract
  • the second component, the second component is cherry plum or cherry plum extract.
  • the weight ratio of the first component and the second component is 1:10-10:1 (such as 1:5-10:1, 1:2-10:1, 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, such as 1:5, 1:2, 1:1, 2:1, 5:1).
  • the red-fleshed apple extract is obtained by one of the following extraction methods: leaching extraction, enzymatic hydrolysis ultrasonic extraction, ultra-high pressure extraction, subcritical extraction or other extraction methods.
  • the red meat apple is selected from the group consisting of: Hong Xun No. 1 (Hong Xun No. 1), Hong Xun No. 3 (Hong Xun No. 3), Hong Xun No. 6 (Hong Xun No. 6), Xia Hong Meat , Daihong, Red Love, Roberts Crab, Red Dream, Ruby Sweet, etc.
  • the present invention provides a combination product comprising:
  • a first product, the first product is the aforementioned composition
  • the second product, the second product is a drug for preventing and/or treating glycemic diseases.
  • the glycemic disorder is selected from diabetes and diabetes-related disorders (eg, type I diabetes, type II diabetes, diabetic nephropathy, etc.).
  • diabetes-related disorders eg, type I diabetes, type II diabetes, diabetic nephropathy, etc.
  • the drugs for preventing and/or treating glycemic diseases are selected from sulfonylurea drugs (such as glipizide, glimepiride, gliclazide, glyburide, etc.), biguanides Drugs (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.
  • sulfonylurea drugs such as glipizide, glimepiride, gliclazide, glyburide, etc.
  • biguanides Drugs metalformin
  • alpha-glucosidase inhibitors a
  • the weight ratio of the first product and the second product is 20000:0.75-20000:600 (eg 20000:0.75, 20000:1.5, 20000:2) 20000:2.5 :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).
  • metformin or dapagliflozin is 20000:0.75-20000:600 (eg 20000:0.75, 20000:1.5, 20000:2) 20000:2.5 :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
  • the weight ratio of the first product to the second product is 20000:75-20000:600 (eg 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).
  • the present invention provides the use of the aforementioned combination product in the preparation of medicine (such as traditional Chinese medicine, Chinese patent medicine, etc.), ordinary food or health food, the medicine (such as traditional Chinese medicine, Chinese patent medicine, etc.), ordinary Foods or health foods are used to lower blood sugar, or to prevent and/or treat blood sugar diseases.
  • medicine such as traditional Chinese medicine, Chinese patent medicine, etc.
  • ordinary food or health food such as traditional Chinese medicine, Chinese patent medicine, etc.
  • ordinary Foods or health foods are used to lower blood sugar, or to prevent and/or treat blood sugar diseases.
  • the present invention provides a method for lowering blood sugar, or preventing and/or treating glycemic diseases, comprising administering the aforementioned composition or the aforementioned combination product to an individual in need thereof.
  • the above-mentioned glycemic diseases are selected from diabetes and diabetes-related diseases (eg, type I diabetes, type II diabetes, diabetic nephropathy, etc.).
  • diabetes-related diseases eg, type I diabetes, type II diabetes, diabetic nephropathy, etc.
  • the invention also discloses a hypoglycemic red-meat apple and cherry plum combination product and a preparation method thereof, including product forms such as fresh fruit, fruit juice, jam, freeze-dried powder, tablet candy, oral liquid, capsule and the like. Animal experiments show that this series of products has a good synergistic hypoglycemic effect.
  • the composition of the present invention can also be used to prepare medicines such as traditional Chinese medicines and Chinese patent medicines.
  • the present application also provides a combination product comprising a first product and a second product individually packaged, the first product being a red meat apple and cherry plum combination product, and the second product being Hypoglycemic drugs (such as sulfonylureas (such as glipizide, glimepiride, gliclazide, glyburide, etc.), biguanides (metformin), alpha-glucosidase inhibitors (acarb Sugar, 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.).
  • Hypoglycemic drugs such as sulfonylureas (such as glipizide, glimepir
  • “individual” includes humans or non-human animals.
  • Exemplary human subjects include human subjects (referred to as patients) or normal subjects with a disease (eg, a disease described herein).
  • “Non-human animals” in the present invention include all vertebrates such as non-mammals (eg fish, birds, amphibians, reptiles) and mammals such as non-human primates, livestock and/or domesticated animals (eg mice, sheep, dogs, cats, cows, pigs, etc.).
  • cherry plum extract or “red flesh apple extract” refers to obtaining and enriching cherry plum or red flesh apple through physical and/or chemical extraction and separation process using cherry plum or red flesh apple as raw material
  • the product formed by one or more active ingredients in the product can be used as the raw material or auxiliary material of food (such as ordinary food or health food) or medicine.
  • Exemplary extraction methods include, but are not limited to: leaching extraction, enzymatic hydrolysis ultrasonic extraction, ultra-high pressure extraction and subcritical extraction.
  • the red flesh apple and cherry plum extracts of the present invention are obtained by leaching extraction (eg, water or alcohol extraction).
  • the leaching extraction comprises the steps of:
  • Step 1 The red-fleshed apples and cherry plums are respectively deseeded or pitted and beaten to obtain pulp directly, or the juice and pomace are separated; in certain embodiments, gauze (such as 100-300 mesh gauze, 200-mesh gauze) filter to separate out fruit juice and pomace;
  • gauze such as 100-300 mesh gauze, 200-mesh gauze
  • Step 2 Mix the pulp or pomace with an extraction medium (such as water or ethanol), and extract (such as 30-100 min, such as 60 min) at room temperature or under heating (such as 10-100° C., such as 50° C.),
  • the pulp or pomace extract is obtained by filtration; in certain embodiments, the pulp or pomace is mixed with the extraction medium in a weight ratio of 1:(2-10) (eg, 1:5); in certain embodiments , the ethanol is 50%-95% ethanol;
  • Step 3 Concentrating the pulp extract or the combined solution of the fruit juice and the pomace extract to obtain the extracts of red-fleshed apples and cherry plums; in some embodiments, concentrated by rotary evaporation; in some In embodiments, the temperature of the rotary evaporation is 30-60°C, eg, 50°C;
  • Step 4 Mix the extracted red meat apple and cherry plum extracts in different proportions (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10: 1) Prepare a composition, or in step 1, mix red-meat apple and cherry plum raw materials in different proportions, and then extract.
  • the red-fleshed apple and cherry plum extracts of the present invention are obtained by water extraction, and in certain embodiments, the water extraction and extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 meshes;
  • Step 2 Red-fleshed apple and cherry plum pulp or pomace are mixed with water at a ratio of 1: (2-10) to water, leaching at 10-100°C for 30-100min, and filtering to obtain pulp or pomace extract ;
  • the ratio of solid to liquid is 1:5; in certain embodiments, the extraction temperature is 50°C; in certain embodiments, the extraction time is 60 min;
  • Step 3 Red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract, concentrated by rotary evaporation at 30-60 ° C, to obtain red-fleshed apple and cherry plum water extract;
  • the rotary evaporation temperature is 50°C;
  • Step 4 Mix the extracted red meat apple and cherry plum water extracts according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1 , 10:1) is prepared into a composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then extracted.
  • the red-fleshed apple and cherry plum extracts of the present invention are obtained by alcohol extraction, and in certain embodiments, the alcohol extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 meshes;
  • Step 2 Red-fleshed apple and cherry plum pulp or pomace are mixed with 50%-95% ethanol according to the ratio of material to liquid 1: (2-10), leaching at 10-100 °C for 30-100min, and filtering to obtain fruit pulp or pomace extract; in certain embodiments, the ratio of solid to liquid is 1:5; in certain embodiments, the concentration of ethanol used is 50%; in certain embodiments, leaching
  • the extraction temperature is 50°C; in some embodiments, the extraction time is 60min;
  • Step 3 The red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract is concentrated by rotary evaporation at 30-60°C, and the pulp extract is directly concentrated to obtain red-flesh apple and cherry plum alcohol leaching Extract the extract; in certain embodiments, the rotary evaporation temperature is selected to be 50°C; optionally, the extract is subjected to a drying treatment to remove residual ethanol therein;
  • Step 4 Mix the red-fleshed apple and cherry plum alcohol extracts obtained by extraction according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1 , 10:1) is prepared into a composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then extracted.
  • the red flesh apple and cherry plum extracts of the present invention are obtained by enzymatic ultrasonic extraction (eg, enzymatic ultrasonic water extraction or enzymatic ultrasonic alcohol extraction).
  • enzymatic ultrasonic extraction eg, enzymatic ultrasonic water extraction or enzymatic ultrasonic alcohol extraction.
  • the enzymatic hydrolysis ultrasonic extraction comprises the following steps:
  • Step 1 The red-fleshed apples and cherry plums are respectively deseeded or pitted and beaten to obtain pulp directly, or the juice and pomace are separated; in certain embodiments, gauze (such as 100-300 mesh gauze, 200-mesh gauze) filter to separate out fruit juice and pomace;
  • gauze such as 100-300 mesh gauze, 200-mesh gauze
  • Step 2 Mix the pulp or pomace with an extraction medium (eg, water or ethanol) and cellulase, and extract under heating conditions (eg, 30-50°C, eg, 45°C) (eg, 30-100 min, eg, 60 min) , and then ultrasonic (such as ultrasonic 20-60min, such as ultrasonic 30min) under ultrasonic conditions (such as ultrasonic power of 100-500W), filter to obtain pulp or pomace extract;
  • the addition of cellulase The amount (based on the weight of the pomace or pulp) is 0.2%-1% (eg 0.5%); in certain embodiments, the pulp or pomace to extraction medium is 1:(2-10) (eg 1 : 5) weight ratio mixing;
  • the ethanol is 50%-95% ethanol;
  • Step 3 Concentrating the red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract to obtain an enzymatic hydrolysis ultrasonic extract of red-fleshed apple and cherry plum; in certain embodiments, by rotating Concentrating by evaporation; in certain embodiments, the temperature of rotary evaporation is 30-60°C, such as 50°C;
  • Step 4 Mix the extracted red meat apple and cherry plum enzymolysis ultrasonic extract according to different ratios (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1 , 10:1) is prepared into a composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then extracted.
  • the red-fleshed apple and cherry plum extracts of the present invention are obtained by enzymatic hydrolysis ultrasonic water extraction, and in certain embodiments, the enzymatic hydrolysis ultrasonic water extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 meshes;
  • Step 2 Mix red-fleshed apple and cherry plum pulp or pomace with water at a ratio of 1:(2-10) to water, and add 0.2%-1% (based on the weight of pomace or pulp) cellulose Enzyme, 30-50°C water bath extraction for 30-100min, 100-500W ultrasonic for 20-60min, filtration to obtain pulp or pomace extract; in certain embodiments, the ratio of material to liquid is 1:5; in certain embodiments In the scheme, the amount of cellulase added is 0.5%; in certain embodiments, the temperature of the water bath is 45°C; in certain embodiments, the extraction time is 60 min; in certain embodiments, the ultrasonic power is 500W; In certain embodiments, the sonication time is 30 min;
  • Step 3 The combined solution of red-fleshed apple and cherry plum pulp or juice and pomace extract is concentrated by rotary evaporation at 30-60 °C to obtain the red-fleshed apple and cherry plum enzymatic hydrolysis ultrasonic extraction water extract;
  • the rotary evaporation temperature is 50°C;
  • Step 4 Mix the extracted red meat apple and cherry plum enzymolysis ultrasonic water extract according to different ratios (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5: 1. 10:1) to prepare a composition, or in step 1, red-fleshed apple and cherry plum raw materials are mixed according to the aforementioned different ratios, and then extracted.
  • the red-fleshed apple and cherry plum extracts of the present invention are obtained by enzymatic hydrolysis ultrasonic alcohol extraction, and in certain embodiments, the enzymatic hydrolysis ultrasonic alcohol extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 meshes;
  • Step 2 Mix red-fleshed apple and cherry plum pulp or pomace with 50%-95% ethanol according to the ratio of material to liquid 1:(2-10), add 0.2%-1% (by weight of pomace or pulp) Be benchmark) cellulase, 30-50 °C of water bath extraction 30-100min, 100-500W ultrasonic 20-60min, filter to obtain pulp or pomace extract;
  • the material-to-liquid ratio is selected 1: 5; in certain embodiments, the concentration of ethanol used is 50%; in certain embodiments, the amount of cellulase added is 0.5%; in certain embodiments, the temperature of the water bath is 45°C;
  • the extraction time is 60min; in some embodiments, the ultrasonic power is 500W; in some embodiments, the ultrasonic time is 30min;
  • Step 3 red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract, concentrated by rotary evaporation at 30-60° C. to obtain red-fleshed apple and cherry plum enzymatic hydrolysis ultrasonic extraction alcohol extract;
  • the rotary evaporation temperature is selected at 50°C; optionally, the extract is subjected to evaporation treatment to remove residual ethanol therein;
  • Step 4 Mix the extracted red meat apple and cherry plum enzymolysis ultrasonic alcohol extract according to different ratios (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5: 1. 10:1) to prepare a composition, or in step 1, red-fleshed apple and cherry plum raw materials are mixed according to the aforementioned different ratios, and then extracted.
  • the red flesh apple and cherry plum extracts of the present invention are obtained by ultra-high pressure extraction (eg, ultra-high pressure water extraction or ultra-high pressure alcohol extraction).
  • ultra-high pressure refers to pressures in excess of 100 MPa (equivalent to 1000 atmospheres).
  • the ultra-high pressure extraction comprises the steps of:
  • Step 1 The red-fleshed apples and cherry plums are respectively deseeded or pitted and beaten to obtain pulp directly, or the juice and pomace are separated; in certain embodiments, gauze (such as 100-300 mesh gauze, 200-mesh gauze) filter to separate out fruit juice and pomace;
  • gauze such as 100-300 mesh gauze, 200-mesh gauze
  • Step 2 Mix the pulp or pomace with an extraction medium (such as water or ethanol), process (such as 3-10min, such as 5min) under ultra-high pressure (such as 200-600MPa, such as 400MPa), and filter to obtain the fruit.
  • pulp or pomace extract in certain embodiments, the pulp or pomace is mixed with the extraction medium in a weight ratio of 1:(2-10) (eg, 1:5); in certain embodiments, the Ethanol is 50%-95% ethanol;
  • Step 3 Concentrating the combined solution of red-fleshed apple and cherry plum pulp or juice and pomace extract to obtain an ultra-high pressure extract of red-fleshed apple and cherry plum; in certain embodiments, concentrated by rotary evaporation ; In certain embodiments, the temperature of the rotary evaporation is 30-60°C, such as 50°C;
  • Step 4 Mix the extracted red meat apple and cherry plum ultra-high pressure extracts according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) Prepare a composition, or in step 1, mix red-meat apple and cherry plum raw materials in different proportions, and then extract.
  • the red-fleshed apple and cherry plum extracts of the present invention are obtained by ultra-high pressure water extraction, and in certain embodiments, the ultra-high pressure water extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 meshes;
  • Step 2 Red-fleshed apple and cherry plum pulp or pomace are mixed with water according to a material-to-liquid ratio of 1: (2-10), treated with ultra-high pressure 200-600MPa for 3-10min, and filtered to obtain pulp or pomace extract;
  • the ratio of material to liquid is 1:5; in certain embodiments, the ultra-high pressure is 400MPa; in certain embodiments, the ultra-high pressure treatment time is 5min;
  • Step 3 Red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract, concentrated by rotary evaporation at 30-60 ° C, to obtain red-fleshed apple and cherry plum ultra-high pressure extraction water extract;
  • the rotary evaporation temperature is selected to be 50 °C;
  • Step 4 Mix the extracted red meat apple and cherry plum ultra-high pressure water extracts according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1 , 10:1) is prepared into a composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then extracted.
  • the red-fleshed apple and cherry plum extracts of the present invention are obtained by ultra-high pressure alcohol extraction, and in certain embodiments, the ultra-high pressure alcohol extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 meshes;
  • Step 2 Red-fleshed apple and cherry plum pulp or pomace are mixed with 50%-95% ethanol according to the ratio of material to liquid 1:(2-10), treated with ultra-high pressure 200-600MPa for 3-10min, and filtered to obtain pulp Or pomace extract; in certain embodiments, the ratio of material to liquid is 1:5; in certain embodiments, the ultra-high pressure is 400MPa; in certain embodiments, the ultra-high pressure treatment time is selected 5min; In some embodiments, the ethanol is 50% ethanol;
  • Step 3 Red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract, concentrated by rotary evaporation at 30-60°C, to obtain red-fleshed apple and cherry plum ultra-high pressure extraction alcohol extract;
  • the rotary evaporation temperature is selected as 50°C; optionally, the extract is subjected to evaporation treatment to remove residual ethanol therein;
  • Step 4 Mix the extracted red meat apple and cherry plum ultra-high pressure alcohol extracts according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1 , 10:1) is prepared into a composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then extracted.
  • red flesh apple and cherry plum extracts are obtained by subcritical extraction (eg, subcritical water extraction or subcritical alcohol extraction).
  • the subcritical extraction comprises the steps of:
  • Step 1 The red-fleshed apples and cherry plums are respectively deseeded or pitted and beaten to obtain pulp directly, or the juice and pomace are separated; in certain embodiments, gauze (such as 100-300 mesh gauze, 200-mesh gauze) filter to separate out fruit juice and pomace;
  • gauze such as 100-300 mesh gauze, 200-mesh gauze
  • Step 3 Concentrating the combined solution of pulp or fruit juice and pomace extract to obtain subcritical extracts of red-fleshed apples and cherry plums; in certain embodiments, concentrated by rotary evaporation; in certain embodiments , the temperature of rotary evaporation is 30-60°C, such as 50°C;
  • Step 4 Mix the extracted red meat apple and cherry plum sub-critical extracts according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) Prepare a composition, or in step 1, mix red-meat apple and cherry plum raw materials in different proportions, and then extract.
  • the red flesh apple and cherry plum extracts of the present invention are obtained by subcritical water extraction, in certain embodiments, the subcritical water extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 mesh;
  • Step 2 Red-fleshed apple and cherry plum pulp or pomace are mixed with water according to the ratio of material to liquid 1: (2-10), subcritically extracted for 10-50min, the treatment temperature is 100-150 °C, filtered to obtain pulp or Pomace extract; in certain embodiments, the ratio of solid to liquid is 1:5; in certain embodiments, the treatment temperature is 110°C; in certain embodiments, the treatment time is 30min;
  • Step 3 Red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract, concentrated by rotary evaporation at 30-60°C, to obtain red-fleshed apple and cherry plum subcritical extraction water extract;
  • the rotary evaporation temperature is selected to be 50 °C;
  • Step 4 Mix the extracted red-fleshed apple and cherry plum subcritical water extracts according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1 , 10:1) is prepared into a composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then extracted.
  • the red flesh apple and cherry plum extracts of the present invention are obtained by subcritical alcohol extraction, and in certain embodiments, the subcritical alcohol extraction comprises the following steps:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums, respectively, and beat the pulp to obtain pulp directly, or filter the juice with 100-300-mesh gauze to obtain red-fleshed apple and cherry plum juice, and separate the juice and the pomace;
  • the mesh of the gauze is 200 mesh;
  • Step 2 Red-fleshed apple and cherry plum pulp or pomace are mixed with 50%-95% ethanol according to the material-to-liquid ratio of 1: (2-10), subcritically extracted for 10-50min, and the processing temperature is 100-150°C, Filtration to obtain pulp or pomace extract; in certain embodiments, the ratio of solid to liquid is 1:5; in certain embodiments, the treatment temperature is 110 ° C; in certain embodiments, the treatment time is 30min ;
  • Step 3 Red-fleshed apple and cherry plum pulp extract or the combined solution of fruit juice and pomace extract, concentrated by rotary evaporation at 30-60°C, to obtain red-fleshed apple and cherry plum subcritical extraction alcohol extract;
  • the rotary evaporation temperature is selected as 50°C; optionally, the extract is subjected to evaporation treatment to remove residual ethanol therein;
  • Step 4 Mix the red-fleshed apple and cherry plum subcritical alcohol extracts according to different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1 , 10:1) is prepared into a composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then extracted.
  • the product form of the composition of the present invention can be fresh fruit, fruit juice, jam, fruit powder (such as freeze-dried powder), candy (such as tablet candy), oral liquid, capsule, tablet, dried fruit, preserved fruit, Fruit wine or pastries.
  • the product form of the composition of the present invention can be medicine, general food or health food.
  • the composition can be used as the main raw material, for example, accounting for more than 30wt%, more than 40wt%, more than 50wt%, more than 60wt%, more than 70wt%, more than 80wt%, more than 90wt% or 100wt% of the total raw materials;
  • the product may also contain other ingredients such as water, sweeteners, or other kinds of fruit or extracts thereof.
  • red meat apple and cherry plum products eg, fresh fruit, juices, jams, lyophilized powders, compressed candies, oral liquids, capsules.
  • red flesh apple and cherry plum fresh fruit can be obtained by a method comprising the steps of:
  • Step 1 Harvest red-fleshed apples and cherry plums from 1 month before maturity to when they are fully mature, and choose to pick fruits on sunny days;
  • Step 2 Pick and remove rotten fruit or fruit with poor color
  • Step 3 Refrigerate storage after harvest
  • Step 4 Combine red-fleshed apples and fresh cherry plums in different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1).
  • the obtained red flesh apple and cherry plum fresh fruit can be eaten directly.
  • Step 3 Mix red meat apple and cherry plum jam in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare The composition, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different proportions, and then beating is performed to prepare jam.
  • red meat apple and cherry plum lyophilized powder can be obtained by a method comprising the steps of:
  • red meat apple and cherry plum lyophilized powder can also be obtained by a method comprising the steps of:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums separately;
  • Step 3 freeze-dry the fruit juice to make fruit juice freeze-dried powder
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums separately;
  • Step 2 Freeze-dry the fruit pulp to make the fruit pulp freeze-dried powder
  • Step 3 freeze-dry the fruit juice to make fruit juice freeze-dried powder
  • Step 4 Compress the fruit juice freeze-dried powder and accessories into tablet candies.
  • Step 5 Mix the red-fleshed apple and cherry plum candies in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1)
  • the composition is prepared, or in step 1, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different ratios, and then the raw materials are beaten to prepare a tablet candy.
  • red meat apple and cherry plum oral liquid can be obtained by a method comprising the steps of:
  • Step 1 Preparation of red meat apple and cherry plum extracts in different ratios (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) , obtained by leaching extraction, enzymatic hydrolysis ultrasonic extraction, ultra-high pressure extraction or subcritical extraction, the steps are the same as above);
  • Step 2 sterilizing the extracts of red-fleshed apples and cherry plums to obtain red-flesh apple oral liquid.
  • red meat apple and cherry plum oral liquid can also be obtained by a method comprising the steps of:
  • Step 1 Preparation of red meat apple and cherry plum extracts in different ratios (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) , obtained by leaching extraction, enzymatic hydrolysis ultrasonic extraction, ultra-high pressure extraction or subcritical extraction, the steps are the same as above);
  • Step 2 adding pectinase enzymatic hydrolysis and filtering to prepare a clear juice extract composition
  • Step 3 sterilizing the extracts of red meat apple and cherry plum juice to obtain red meat apple oral liquid.
  • red meat apple and cherry plum capsules can be obtained by a method comprising the steps of:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums separately;
  • Step 2 Freeze-dry the fruit pulp to make the fruit pulp freeze-dried powder
  • Step 4 Pack the lyophilized fruit pulp into the capsule shell to make capsules.
  • red meat apple and cherry plum capsules can also be obtained by a method comprising the steps of:
  • Step 1 Deseed or pit the red-fleshed apples and cherry plums separately;
  • Step 2 filter the slurry (for example, filter with 100-300 mesh gauze) to obtain red meat apple and cherry plum juice; in certain embodiments, the mesh of the gauze is 200 mesh;
  • Step 3 freeze-dry the fruit juice to make fruit juice freeze-dried powder
  • Step 4 Mix red meat apple and cherry plum freeze-dried powder in different ratios (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) Prepare a composition, or in step 1, mix red-meat apples and cherry plum raw materials in different proportions, and then beating to prepare freeze-dried powder;
  • Step 5 Pack the fruit juice freeze-dried powder into the capsule shell to make capsules.
  • the present invention selects natural red meat apple and cherry plum, and the prepared red meat apple and cherry plum combination product has good hypoglycemic effect, and the effect of the combination of the two is better than that of using red meat apple or cherry plum alone, and has synergistic effect. effect.
  • the effect of the combination of the composition and the drug is better than that of the composition or the drug alone.
  • Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are harvested from 1 month before maturity to when they are fully mature.
  • priority is given to picking fruits on sunny days, and rotten fruits or fruits with poor color are selected and removed.
  • the obtained red-fleshed apples and cherry plums are combined in different ratios (weight ratios) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1), and the fresh fruits can be directly edible.
  • the red meat apple and cherry plum products described in this example refer to the red meat apple and cherry plum juice cloudy juice.
  • the red meat apple and cherry plum products described in this embodiment refer to the red meat apple and cherry plum juice clear juice.
  • red meat apple and cherry plum products described in this example refer to red meat apple and cherry plum jam.
  • Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are seeded or pitted, beaten, boiled and heated to make a thick jam.
  • the red meat apple and cherry plum jam are mixed in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a composition, Or firstly, the raw materials of red meat apple and cherry plum are mixed according to the aforementioned different proportions, and then the jam is prepared by beating.
  • the red meat apple and cherry plum products described in this example refer to the freeze-dried powder of red meat apple and cherry plum.
  • Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are seeded or pitted, beaten and then freeze-dried to produce freeze-dried powder.
  • Red meat apple and cherry plum freeze-dried powder are mixed in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a combination or mix the raw materials of red meat apples and cherry plums according to the aforementioned different proportions, and then beating to prepare freeze-dried powder.
  • red-fleshed apple and cherry plum products described in this example refer to red-fleshed apple and cherry plum pressed candies.
  • Red-fleshed apples (Hongxun No. 1) and cherry plums (black fruit) are seeded or pitted and beaten, freeze-dried to make pulp freeze-dried powder, and the pulp freeze-dried powder and accessories are compressed to make tablet candy.
  • the red meat apple and cherry plum pressed candies are mixed in different proportions (weight ratio) (1:10, 1:5, 1:2, 1:1, 2:1, 5:1, 10:1) to prepare a combination
  • the raw materials of red meat apples and cherry plums are mixed according to the aforementioned different proportions, and then beaten to prepare tablet candies.
  • the red-fleshed apple and cherry plum products described in this example refer to the water-extracted oral liquid of red-fleshed apple and cherry plum.
  • Red-fleshed apples Haongxun No. 1
  • cherry plums black fruit
  • the red-fleshed apple and cherry plum products described in this example refer to the water-extracted oral liquid of red-fleshed apple (red love) and cherry plum (red fruit).
  • the preparation steps are the same as those in Example 7.
  • the red-fleshed apple and cherry plum products described in this example refer to the alcohol extraction oral liquid of red-fleshed apple (Hongxun No. 1) and cherry plum (black fruit).
  • red-fleshed apple and cherry plum products described in this embodiment refer to the oral liquid for the enzymatic hydrolysis of red-fleshed apple and cherry plum and ultrasonic water extraction.
  • Red-fleshed apples Haongxun No. 1
  • cherry plums black fruit
  • red-fleshed apple and cherry plum products described in this example refer to the oral liquid extracted from red-fleshed apple (Hongxun No. 3) and cherry plum (red fruit) by enzymatic hydrolysis and ultrasonic water extraction.
  • the preparation steps are the same as those in Example 10.
  • red-fleshed apple and cherry plum products described in this example refer to the red-fleshed apple (Hongxun No. 1) and the cherry plum (black fruit) enzymatic hydrolysis ultrasonic alcohol extraction oral liquid.
  • the red meat apple and cherry plum products described in this embodiment refer to the ultra-high pressure water extraction oral liquid of red meat apple and cherry plum.
  • Red-fleshed apples Haongxun No. 1
  • cherry plums black fruit
  • red-fleshed apple and cherry plum products described in this example refer to the ultra-high pressure water extraction oral liquid of red-fleshed apple (Hongxun No. 6) and cherry plum (red fruit).
  • the preparation steps are the same as those in Example 13.
  • the red-fleshed apple and cherry plum products described in this example refer to the ultra-high pressure alcohol extraction oral liquid of red-fleshed apple (Hongxun No. 1) and cherry plum (black fruit).
  • Example 13 Refer to the steps (1)-(5) of Example 13, wherein the fruit pulp is added 50% according to the ratio of material to liquid 1:5. Alcohol extracts were treated with ethanol to evaporate.
  • the red meat apple and cherry plum products described in this example refer to the subcritical water extraction oral liquid of red meat apple and cherry plum.
  • Red-fleshed apples Haongxun No. 1
  • cherry plums black fruit
  • Zebrafish larvae with embryonic development phase of 5dpf were selected and divided into model group, control group, positive drug group (metformin) and sample group.
  • the model group, the positive drug group and the sample group were soaked in glucose solution and fed with high-fat diet; the control group was cultured with system water and fed with high-fat diet. Feed the juveniles 2 times a day.
  • the positive drug group was given metformin, and the sample group was given the test sample.
  • juvenile fish were collected, ground and water added, and the glucose content in total tissue fluid was measured with a blood glucose meter.
  • Blood glucose inhibition rate (%) (blood glucose of model group-blood glucose of drug group)/blood glucose of model group ⁇ 100
  • the test results are shown in Table 1 below.
  • the samples of the red-fleshed apple group and the cherry plum group alone are the red-fleshed apple enzymolysis ultrasonic water extract and the cherry plum enzymolysis ultrasonic water extract obtained in step (3) of Example 10, respectively.
  • the samples of the red-fleshed apple and cherry plum composition group are the compositions of each weight ratio prepared in step (4) of Example 10.
  • each group is shown with a single underline, wherein: 1 mg/mL or 0.5 mg/mL represents the concentration of the positive drug dispersed in water; 0.01% represents the red meat apple enzymatic hydrolysis ultrasonic water extract, or cherry plum enzyme The concentration of the hydrolyzed ultrasonic water extract, or the composition consisting of the red meat apple enzymatic hydrolysis ultrasonic water extract and the cherry plum enzymatic ultrasonic water extract in different weight ratios dispersed in water.
  • the red-fleshed apple and cherry plum composition had an additive effect (0.85 ⁇ q ⁇ 1.15) when used in combination with the positive drug.
  • the hypoglycemic effect of the combination of the composition and the positive drug is better than the effect of single use. Combination with lower doses of positive drugs can significantly improve the effect.
  • Healthy db/db mice were taken and divided into positive drug group (metformin, dapagliflozin), model group and sample group; a normal control group was also set up, and the normal control group was C57 wild-type mice with BKS background; Group of 20.
  • the model group was given distilled water (0.5mL/mice)
  • the positive drug group was given metformin or dapagliflozin
  • the sample group was given samples (0.5mL/meat), and the experimental period was 14 days.
  • the blood glucose content of the mice was measured with a blood glucose meter after the blood was drawn from the tail tip.
  • Blood glucose inhibition rate (%) (blood glucose value in model group - blood glucose value in drug group)/blood glucose value in model group ⁇ 100
  • test results are shown in Table 2 below.
  • the samples of the red-fleshed apple group and the cherry plum group alone are the red-fleshed apple enzymolysis ultrasonic water extract and the cherry plum enzymolysis ultrasonic water extract obtained in step (3) of Example 10, respectively.
  • the samples of the red-fleshed apple and cherry plum composition group are the compositions of each weight ratio prepared in step (4) of Example 10.
  • the dose administered corresponding to each group is shown with a single underline.
  • the blood sugar inhibition rate of the red meat apple and cherry plum composition (10:1-1:10) is higher than the numerical value when used alone, and the calculated q value is all greater than 1.15, indicating that there is a synergistic effect.
  • the red-fleshed apple and cherry plum composition had an additive effect (0.85 ⁇ q ⁇ 1.15) when used in combination with the positive drug.

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Abstract

一种具有降血糖功效的红肉苹果和樱桃李组合物，所述的红肉苹果和樱桃李的重量比为1:10-10:1。所述组合物在制备药物(如中药、中成药等)、普通食品或保健食品中的用途，所述药物(如中药、中成药等)、普通食品或保健食品用于降血糖或者用于预防和/或治疗血糖性疾病。

Description

红肉苹果和樱桃李组合物及其在降血糖方面的应用 技术领域
本发明涉及食品和药品领域，具体涉及红肉苹果和樱桃李组合物及其在降血糖方面的应用。
背景技术
糖尿病是一组因胰岛素绝对或相对分泌不足和(或)胰岛素利用障碍引起的以高血糖为特征的代谢性疾病。国际糖尿病联盟(IDF)2017年统计数据显示，中国成年人的糖尿病患病率为9.7％～11.6％，糖尿病患病人群约1.1亿，居世界首位。
目前尚无根治糖尿病的方法，临床上用于治疗糖尿病的药物主要有磺脲类药物(如格列吡嗪、格列美脲、格列齐特、格列苯脲等)、双胍类药物(二甲双胍)、α-糖苷酶抑制剂(阿卡波糖、伏格列波糖)、胰岛素增敏剂(罗格列酮、吡格列酮等)、胰岛素促泌剂(苯甲酸衍生物)，DPP-4抑制剂(沙格列汀、西格列汀等)，SGLT-2抑制剂(达格列净、恩格列净等)，此外还有胰岛素治疗方式。但降血糖治疗共同的严重副作用为低血糖。α-糖苷酶抑制剂、双胍类及胰岛素增收剂单独使用一般不会引起低血糖，但与其他药物连用时仍可能发生。双胍类的降糖药对肠胃的伤害较大。因此有必要寻找效果好且无副作用的天然资源，以用于糖尿病的防治。
红肉苹果(Malus neidzwetzkyana Dieck)是蔷薇科(Rosaceae)苹果属(Malus Mill)植物，其果实的果肉呈红色，果实的颜色主要是由花色苷的积累造成的。目前世界各地有众多红肉苹果品种，例如中国新疆的洪勋系列、美国的Robert Crab、日本的红宝石甜、瑞士的红色之爱(Redlove)等。红肉苹果各品种的花、枝叶颜色、果实大小、着色程度、口感风味等各不相同。新疆的红肉苹果在红果肉苹果属植物起源中有着重要的地位。
樱桃李(Prunus cerasifera Ehrhart)，俗称野酸梅，蔷薇科李属，是世界上极为珍贵和罕见并濒危灭绝的原始野生林果。据《中国树木志》的记载和国家野生植物研究院的考证，野生樱桃李仅发现在新疆天山山脉西部及高加索、小亚西亚山地生存，野生资源极为稀少。樱桃李果实在我国新疆地区有着悠久的食用历史，居住在天山大西沟的哈萨克族、蒙古族牧民饮食以牛羊肉为主，其人群中患高血脂、高血压的人却很少，这与牧民长期采摘野生樱桃李制作果酱或将果实晒干泡茶的使用习惯有关。樱 桃李包括多个品种，按照颜色分主要有黑果、红果、紫果、紫黑果、黄果等。
红肉苹果和樱桃李富含多种氨基酸、维生素、矿物质，以及花色苷、多酚、类黄酮等功能成分，具有较高的开发价值。但目前的研究仍较有限，主要集中在化学成分及抗氧化方面，还处于初步研究阶段。
发明内容
本申请发明人经过大量的实验研究后发现，红肉苹果(或红肉苹果提取物)和樱桃李(或樱桃李提取物)的组合在降血糖方面具有协同增效作用。
为此，在本发明的第一方面，本发明提供了组合物在制备药物(如中药、中成药等)、普通食品或保健食品中的用途，所述药物(如中药、中成药等)、普通食品或保健食品用于降血糖或者用于预防和/或治疗血糖性疾病，其中，所述组合物包含：
第一组分，所述第一组分为红肉苹果或红肉苹果提取物；和
第二组分，所述第二组分为樱桃李或樱桃李提取物。
在一些实施方案中，所述血糖性疾病选自糖尿病及糖尿病相关疾病(如I型糖尿病、II型糖尿病、糖尿病肾病等)。
在一些实施方案中，所述第一组分和所述第二组分的重量比为1:10-10:1(如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，具体如1:5，1:2，1:1，2:1，5:1)。
在一些实施方案中，所述红肉苹果提取物通过以下提取方式之一获得：浸提提取、酶解超声提取、超高压提取、亚临界提取或其他提取方式。
在一些实施方案中，所述樱桃李提取物通过以下提取方式之一获得：浸提提取、酶解超声提取、超高压提取、亚临界提取或其他提取方式。
在一些实施方案中，所述组合物是以鲜果、果汁、果酱、果粉(如冻干粉)、糖果(如压片糖果)、口服液、胶囊、片剂、果干、果脯、果酒或糕点等形式存在的。换句话说，所述组合物的产品形式可以是鲜果、果汁、果酱、果粉(如冻干粉)、糖果(如压片糖果)、口服液、胶囊、片剂、果干、果脯、果酒或糕点等。也就是说，所述组合物可以制成鲜果、果汁、果酱、果粉(如冻干粉)、糖果(如压片糖果)、口服液、胶囊、片剂、果干、果脯、果酒或糕点等。
在一些实施方案中，所述红肉苹果是指果肉为红色的蔷薇科苹果属植物的果实。
在一些实施方案中，所述红肉苹果选自：洪勋1号(红勋1号)、洪勋3号(红勋3号)、洪勋6号(红勋6号)、夏红肉、黛红、红色之爱、Roberts Crab、红之梦、红宝石甜等。
在一些实施方案中，所述樱桃李选自樱桃李红果、樱桃李黑果、樱桃李紫果、樱桃李紫黑果、樱桃李黄果等。
在本发明的第二方面，本发明提供了组合产品，其包括：
第一产品，所述第一产品为前述的组合物；
第二产品，所述第二产品为预防和/或治疗血糖性疾病的药物。
在一些实施方案中，所述血糖性疾病选自糖尿病及糖尿病相关疾病(如I型糖尿病、II型糖尿病、糖尿病肾病等)。
在一些实施方案中，所述预防和/或治疗血糖性疾病的药物选自磺脲类药物(如格列吡嗪、格列美脲、格列齐特、格列苯脲等)、双胍类药物(二甲双胍)、α-糖苷酶抑制剂(阿卡波糖、伏格列波糖)、胰岛素增敏剂(罗格列酮、吡格列酮等)、胰岛素促泌剂(苯甲酸衍生物)，DPP-4抑制剂(沙格列汀、西格列汀等)，SGLT-2抑制剂(达格列净、恩格列净等)，胰岛素等。
在一些实施方案中，所述第一产品和所述第二产品(如二甲双胍或达格列净)的重量比为20000:0.75-20000:600(如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；或者如20000：1.5-20000:300；或者如20000:150-20000:300，具体如20000:150、20000:200、20000:250或20000:300；或者如20000:1.5-20000:3，具体如20000:1.5、20000:2、20000:2.5或20000:3)。
在一些实施方案中，所述第二产品为二甲双胍时，所述第一产品和所述第二产品的重量比为20000:75-20000:600(如20000:75、20000:150、20000:200、20000:250、20000:300、20000:350、20000:400、20000:450、20000:500、20000:550、20000:600；或者如20000:150-20000:300，具体如20000:150、20000:200、20000:250、20000:300)。
在一些实施方案中，所述第二产品为达格列净时，所述第一产品和所述第二产品的重量比为20000:0.75-20000:6(如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；或者如20000:1.5-20000:3， 具体如20000:1.5、20000:2、20000:2.5、20000:3)。
在本发明的第三方面，本发明提供了前述的组合产品在制备药物(如中药、中成药等)、普通食品或保健食品中的用途，所述药物(如中药、中成药等)、普通食品或保健食品用于降血糖，或者用于预防和/或治疗血糖性疾病。
在本发明的第四方面，本发明提供了前述的组合物或前述的组合产品，其用于降血糖，或者用于预防和/或治疗血糖性疾病。
在本发明的第五方面，本发明提供了降血糖，或者预防和/或治疗血糖性疾病的方法，其包括给有此需要的个体服用前述的组合物或前述的组合产品。
在一些实施方案中，上述血糖性疾病选自糖尿病及糖尿病相关疾病(如I型糖尿病、II型糖尿病、糖尿病肾病等)。
另外，本发明还公开了降血糖的红肉苹果和樱桃李组合产品及其制备方法，包括鲜果、果汁、果酱、冻干粉、压片糖果、口服液、胶囊等产品形式。动物实验表明，该系列产品具有很好的协同降血糖效果。在某些实施例中，本发明的组合物还可用于制备中药、中成药等药物。
另外，在一个方面，本申请还提供了一种组合产品，其包含独立包装的第一产品和第二产品，所述第一产品为红肉苹果和樱桃李组合产品，所述第二产品为降血糖药物(例如磺脲类药物(如格列吡嗪、格列美脲、格列齐特、格列苯脲等)、双胍类药物(二甲双胍)、α-糖苷酶抑制剂(阿卡波糖、伏格列波糖)、胰岛素增敏剂(罗格列酮、吡格列酮等)、胰岛素促泌剂(苯甲酸衍生物)，DPP-4抑制剂(沙格列汀、西格列汀等)，SGLT-2抑制剂(达格列净、恩格列净等)，胰岛素等)。
本发明中，“个体”包括人或非人动物。示例性人个体包括患有疾病(例如本文所述的疾病)的人个体(称为患者)或正常个体。本发明中“非人动物”包括所有脊椎动物，例如非哺乳动物(例如鱼类、鸟类、两栖动物、爬行动物)和哺乳动物，例如非人灵长类、家畜和/或驯化动物(例如鼠、绵羊、犬、猫、奶牛、猪等)。
本发明中，“樱桃李提取物”或者“红肉苹果提取物”是指以樱桃李或红肉苹果为原料，经过物理和/或化学提取分离过程，获取和富集樱桃李或红肉苹果中的一种或多种有效成分而形成的产物，其可以作为食品(例如普通食品或保健食品)或药品的原料或辅料。示例性的提取方式包括但不限于：浸提提取、酶解超声提取、超高压提取和亚临界提取。
以下提供示例性的制备红肉苹果和樱桃李提取物的方法。
浸提提取
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过浸提提取(例如水浸提或醇浸提提取)得到。
在某些实施方案中，所述浸提提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者分离出果汁和果渣；在某些实施方案中，利用纱布(例如100-300目纱布，例如200目纱布)过滤分离出果汁和果渣；
步骤2：将果浆或者果渣与提取介质(例如水或乙醇)混合，在常温或加热(例如，10-100℃，例如50℃)条件下提取(例如提取30-100min，例如60min)，过滤得到果浆或果渣提取液；在某些实施方案中，果浆或果渣与提取介质以1：(2-10)(例如1:5)的重量比混合；在某些实施方案中，所述乙醇为50％-95％的乙醇；
步骤3：将果浆提取液或者果汁与果渣提取液的合并液进行浓缩，得到红肉苹果和樱桃李的浸提提取物；在某些实施方案中，通过旋转蒸发进行浓缩；在某些实施方案中，旋转蒸发的温度为30-60℃，例如50℃；
步骤4：将提取得到的红肉苹果和樱桃李提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过水浸提提取得到，在某些实施方案中，所述水浸提提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所述纱布的目数选取200目；
步骤2：红肉苹果和樱桃李果浆或者果渣按料液比1：(2-10)与水混合，10-100℃浸提提取30-100min，过滤制得果浆或果渣提取液；在某些实施方案中，所述料液比选取1:5；在某些实施方案中，浸提提取温度选取50℃；在某些实施方案中，提取时间选取60min；
步骤3：红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，制得红肉苹果和樱桃李水浸提提取物；在某些实施方案中，旋转蒸发温度选取50℃；
步骤4：将提取得到的红肉苹果和樱桃李水浸提提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过醇浸提提取得到，在某些实施方案中，所述醇浸提提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所述纱布的目数选取200目；
步骤2：红肉苹果和樱桃李果浆或者果渣按料液比1：(2-10)与50％-95％的乙醇混合，10-100℃浸提提取30-100min，过滤制得果浆或果渣提取液；在某些实施方案中，所述料液比选取1:5；在某些实施方案中，所使用的乙醇的浓度为50％；在某些实施方案中，浸提提取温度选取50℃；在某些实施方案中，提取时间选取60min；
步骤3：红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，果浆提取液直接浓缩，制得红肉苹果和樱桃李醇浸提提取物；在某些实施方案中，旋转蒸发温度选取50℃；任选地，对提取物进行挥干处理以除去其中残留的乙醇；
步骤4：将提取得到的红肉苹果和樱桃李醇浸提提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
酶解超声提取
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过酶解超声提取(例如酶解超声水提取或酶解超声醇提取)得到。
在某些实施方案中，所述酶解超声提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者分离出果汁和果渣；在某些实施方案中，利用纱布(例如100-300目纱布，例如200目纱布)过滤分离出果汁和果渣；
步骤2：将果浆或果渣与提取介质(例如水或乙醇)和纤维素酶混合，在加热条件(例如30-50℃，例如45℃)下提取(例如提取30-100min，例如60min)，继而在超声条件(例如100-500W的超声功率)下超声(例如超声20-60min，例如超声30min)，过滤得到果浆或果渣提取液；在某些实施方案中，纤维素酶的添加量(以果渣或果浆重量为基准)为0.2％-1％(例如0.5％)；在某些实施方案中，果浆或果渣与提取介质以1：(2-10)(例如1:5)的重量比混合；在某些实施方案中，所述乙醇为50％-95％的乙醇；
步骤3：将红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液进行浓缩，得到红肉苹果和樱桃李的酶解超声提取物；在某些实施方案中，通过旋转蒸发进行浓缩；在 某些实施方案中，旋转蒸发的温度为30-60℃，例如50℃；
步骤4：将提取得到的红肉苹果和樱桃李酶解超声提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过酶解超声水提取得到，在某些实施方案中，所述酶解超声水提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所述纱布的目数选取200目；
步骤2：将红肉苹果和樱桃李果浆或果渣按料液比1：(2-10)与水混合，添加0.2％-1％(以果渣或果浆重量为基准)的纤维素酶，30-50℃水浴提取30-100min，100-500W超声20-60min，过滤制得果浆或果渣提取液；在某些实施方案中，料液比选取1:5；在某些实施方案中，纤维素酶添加量为0.5％；在某些实施方案中，水浴温度为45℃；在某些实施方案中，提取时间选取60min；在某些实施方案中，超声功率为500W；在某些实施方案中，超声时间为30min；
步骤3：红肉苹果和樱桃李果浆或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，制得红肉苹果和樱桃李酶解超声提取水提取物；在某些实施方案中，旋转蒸发温度选取50℃；
步骤4：将提取得到的红肉苹果和樱桃李酶解超声水提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过酶解超声醇提取得到，在某些实施方案中，所述酶解超声醇提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所述纱布的目数选取200目；
步骤2：将红肉苹果和樱桃李果浆或果渣按料液比1：(2-10)与50％-95％的乙醇混合，添加0.2％-1％(以果渣或果浆重量为基准)的纤维素酶，30-50℃水浴提取30-100min，100-500W超声20-60min，过滤制得果浆或果渣提取液；在某些实施方案中，料液比选取1:5；在某些实施方案中，所使用的乙醇的浓度为50％；在某些实施方案中，纤维素酶添 加量为0.5％；在某些实施方案中，水浴温度为45℃；在某些实施方案中，提取时间选取60min；在某些实施方案中，超声功率为500W；在某些实施方案中，超声时间为30min；
步骤3：红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，制得红肉苹果和樱桃李酶解超声提取醇提取物；在某些实施方案中，旋转蒸发温度选取50℃；任选地，对提取物进行挥干处理以除去其中残留的乙醇；
步骤4：将提取得到的红肉苹果和樱桃李酶解超声醇提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
超高压提取
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过超高压提取(例如超高压水提取或超高压醇提取)得到。如本文中使用的，“超高压”指的是压强超过100MPa(相当于1000个大气压)。
在某些实施方案中，所述超高压提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者分离出果汁和果渣；在某些实施方案中，利用纱布(例如100-300目纱布，例如200目纱布)过滤分离出果汁和果渣；
步骤2：将果浆或果渣与提取介质(例如水或乙醇)混合，在超高压(例如200-600MPa，例如400MPa)条件下处理(例如处理3-10min，例如处理5min)，过滤得到果浆或果渣提取液；在某些实施方案中，果浆或果渣与提取介质以1：(2-10)(例如1:5)的重量比混合；在某些实施方案中，所述乙醇为50％-95％的乙醇；
步骤3：将红肉苹果和樱桃李果浆或果汁与果渣提取液的合并液进行浓缩，得到红肉苹果和樱桃李的超高压提取物；在某些实施方案中，通过旋转蒸发进行浓缩；在某些实施方案中，旋转蒸发的温度为30-60℃，例如50℃；
步骤4：将提取得到的红肉苹果和樱桃李超高压提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过超高压水提取得到，在某些实施方案中，所述超高压水提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所 述纱布的目数选取200目；
步骤2：红肉苹果和樱桃李果浆或果渣按料液比1：(2-10)与水混合，超高压200-600MPa处理3-10min，过滤制得果浆或果渣提取液；在某些实施方案中，料液比选取1:5；在某些实施方案中，超高压压力为400MPa；在某些实施方案中，超高压处理时间选取5min；
步骤3：红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，制得红肉苹果和樱桃李超高压提取水提取物；在某些实施方案中，旋转蒸发温度选取50℃；
步骤4：将提取得到的红肉苹果和樱桃李超高压水提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过超高压醇提取得到，在某些实施方案中，所述超高压醇提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所述纱布的目数选取200目；
步骤2：红肉苹果和樱桃李果浆或果渣按料液比1：(2-10)与50％-95％的乙醇混合，超高压200-600MPa处理3-10min，过滤制得果浆或果渣提取液；在某些实施方案中，料液比选取1:5；在某些实施方案中，超高压压力为400MPa；在某些实施方案中，超高压处理时间选取5min；在某些实施方案中，所述乙醇为50％的乙醇；
步骤3：红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，制得红肉苹果和樱桃李超高压提取醇提取物；在某些实施方案中，旋转蒸发温度选取50℃；任选地，对提取物进行挥干处理以除去其中残留的乙醇；
步骤4：将提取得到的红肉苹果和樱桃李超高压醇提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
亚临界提取(又称“亚临界萃取”)
在某些实施方案中，红肉苹果和樱桃李提取物通过亚临界提取(例如亚临界水提取或亚临界醇提取)得到。
在某些实施方案中，所述亚临界提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者分离出果 汁和果渣；在某些实施方案中，利用纱布(例如100-300目纱布，例如200目纱布)过滤分离出果汁和果渣；
步骤2：将果浆或果渣与提取介质(例如水或乙醇)混合，进行亚临界萃取处理(例如处理10-50min例如30min)，过滤得到果浆或果渣提取液；在某些实施方案中，果浆或果渣与提取介质以1：(2-10)(例如1:5)的重量比混合；在某些实施方案中，所述乙醇为50％-95％的乙醇；在某些实施方案中，亚临界萃取的处理温度为100-150℃(例如110℃)；
步骤3：将果浆或果汁与果渣提取液的合并液进行浓缩，得到红肉苹果和樱桃李的亚临界提取物；在某些实施方案中，通过旋转蒸发进行浓缩；在某些实施方案中，旋转蒸发的温度为30-60℃，例如50℃；
步骤4：将提取得到的红肉苹果和樱桃李亚临界提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过亚临界水提取得到，在某些实施方案中，所述亚临界水提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所述纱布的目数为200目；
步骤2：红肉苹果和樱桃李果浆或果渣按料液比1：(2-10)与水混合，亚临界萃取10-50min，处理温度为100-150℃，过滤制得果浆或果渣提取液；在某些实施方案中，料液比选取1:5；在某些实施方案中，处理温度为110℃；在某些实施方案中，处理时间为30min；
步骤3：红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，制得红肉苹果和樱桃李亚临界提取水提取物；在某些实施方案中，旋转蒸发温度选取50℃；
步骤4：将提取得到的红肉苹果和樱桃李亚临界水提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
在某些实施方案中，本发明的红肉苹果和樱桃李提取物通过亚临界醇提取得到，在某些实施方案中，所述亚临界醇提取包括以下步骤：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，直接获得果浆，或者用100-300目纱布过滤果汁，制得红肉苹果和樱桃李果汁，分离果汁和果渣；在某些实施方案中，所 述纱布的目数为200目；
步骤2：红肉苹果和樱桃李果浆或果渣按料液比1：(2-10)与50％-95％的乙醇混合，亚临界萃取10-50min，处理温度为100-150℃，过滤制得果浆或果渣提取液；在某些实施方案中，料液比选取1:5；在某些实施方案中，处理温度为110℃；在某些实施方案中，处理时间为30min；
步骤3：红肉苹果和樱桃李果浆提取液或果汁与果渣提取液的合并液，在30-60℃旋转蒸发浓缩，制得红肉苹果和樱桃李亚临界提取醇提取物；在某些实施方案中，旋转蒸发温度选取50℃；任选地，对提取物进行挥干处理以除去其中残留的乙醇；
步骤4：将提取得到的红肉苹果和樱桃李亚临界醇提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行提取。
如前所述，本发明的组合物的产品形式可以是鲜果、果汁、果酱、果粉(如冻干粉)、糖果(如压片糖果)、口服液、胶囊、片剂、果干、果脯、果酒或糕点。另外，本发明的组合物的产品形式可以是药品、普通食品或保健食品。在一些实施方案中，果汁、果酱、果粉(如冻干粉)、糖果(如压片糖果)、口服液、胶囊、片剂、果干、果脯、果酒或糕点等产品形式中，本发明的组合物可以作为主要原料，例如，占总原料的30wt％以上、40wt％以上、50wt％以上、60wt％以上、70wt％以上、80wt％以上、90wt％以上或100wt％；任选地，所述产品还可以包含例如水、甜味物质等其他成分，或其他种类水果或其提取物。
以下提供示例性的制备红肉苹果和樱桃李产品(例如鲜果、果汁、果酱、冻干粉、压片糖果、口服液、胶囊)的方法。
鲜果
在某些实施方案中，红肉苹果和樱桃李鲜果可以通过包含以下步骤的方法得到：
步骤1：在成熟前1个月至完全成熟时采收红肉苹果和樱桃李，采果时优先选择晴天采果；
步骤2：挑选并去除烂果或颜色较差的果；
步骤3：采后冷藏存放；
步骤4：将红肉苹果和樱桃李鲜果按照不同比例(重量比)组合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)。
获得的红肉苹果和樱桃李鲜果可供直接食用。
果汁
在某些实施方案中，红肉苹果和樱桃李果汁可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：对浆料进行过滤(例如用100-300目纱布过滤)，制得红肉苹果和樱桃李果汁浊汁；在某些实施方案中，所述纱布的目数为200目；
步骤3：将红肉苹果和樱桃李浊汁按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备果汁。
在某些实施方案中，红肉苹果和樱桃李果汁还可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：对浆料进行过滤(例如用100-300目纱布过滤)，加果胶酶酶解过滤；制得红肉苹果和樱桃李果汁清汁；在某些实施方案中，所述纱布的目数为200目；
步骤3：将红肉苹果和樱桃李清汁按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备果汁。
果酱
在某些实施方案中，红肉苹果和樱桃李果酱可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：将果浆水煮加热浓缩制成红肉苹果和樱桃李果酱；
步骤3：将红肉苹果和樱桃李果酱按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备果酱。
冻干粉
在某些实施方案中，红肉苹果和樱桃李冻干粉可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆，
步骤2：将果浆冷冻干燥制成果浆冻干粉；
步骤3：将红肉苹果和樱桃李冻干粉按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备冻干粉。
在某些实施方案中，红肉苹果和樱桃李冻干粉还可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：对浆料进行过滤(例如用100-300目纱布过滤)，制得红肉苹果和樱桃李果汁；在某些实施方案中，所述纱布的目数为200目；
步骤3：将果汁冷冻干燥制成果汁冻干粉；
步骤4：将红肉苹果和樱桃李冻干粉按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备冻干粉。
压片糖果
在某些实施方案中，红肉苹果和樱桃李压片糖果可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：将果浆冷冻干燥制成果浆冻干粉；
步骤3：对果浆冻干粉和辅料进行压片制成压片糖果；
步骤4：将红肉苹果和樱桃李压片糖果按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备压片糖果。
在某些实施方案中，红肉苹果和樱桃李压片糖果还可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：对浆料进行过滤(例如用100-300目纱布过滤)，制得红肉苹果果汁；在某些实施方案中，所述纱布的目数为200目；
步骤3：将果汁冷冻干燥制成果汁冻干粉；
步骤4：对果汁冻干粉和辅料进行压片制成压片糖果。
步骤5：将红肉苹果和樱桃李压片糖果按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备压片糖果。
口服液
在某些实施方案中，红肉苹果和樱桃李口服液可以通过包含以下步骤的方法得到：
步骤1：制备不同比例(重量比)(1:10、1:5、1:2、1:1、2:1、5:1、10:1)的红肉苹果和樱桃李提取物(例如，通过浸提提取、酶解超声提取、超高压提取或亚临界提取制得，步骤同上文)；
步骤2：对红肉苹果和樱桃李提取物进行灭菌制得红肉苹果口服液。
在某些实施方案中，红肉苹果和樱桃李口服液还可以通过包含以下步骤的方法得到：
步骤1：制备不同比例(重量比)(1:10、1:5、1:2、1:1、2:1、5:1、10:1)的红肉苹果和樱桃李提取物(例如，通过浸提提取、酶解超声提取、超高压提取或亚临界提取制得，步骤同上文)；
步骤2：加果胶酶酶解过滤制备清汁提取物组合物；
步骤3：对红肉苹果和樱桃李清汁提取物进行灭菌制得红肉苹果口服液。
胶囊
在某些实施方案中，红肉苹果和樱桃李胶囊可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：将果浆冷冻干燥制成果浆冻干粉；
步骤3：将红肉苹果和樱桃李冻干粉按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备冻干粉；
步骤4：将果浆冻干粉装入胶囊壳，制成胶囊。
在某些实施方案中，红肉苹果和樱桃李胶囊还可以通过包含以下步骤的方法得到：
步骤1：分别将红肉苹果和樱桃李去籽或去核后打浆；
步骤2：对浆料进行过滤(例如用100-300目纱布过滤)，制得红肉苹果和樱桃李果汁；在某些实施方案中，所述纱布的目数为200目；
步骤3：将果汁冷冻干燥制成果汁冻干粉；
步骤4：将红肉苹果和樱桃李冻干粉按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者在步骤1先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备冻干粉；
步骤5：将果汁冻干粉装入胶囊壳，制成胶囊。
有益效果
本发明选用天然红肉苹果和樱桃李，制备的红肉苹果和樱桃李组合产品具有很好的降血糖作用，两种复配的效果优于单独使用红肉苹果或樱桃李，具有协同增效作用。组合物与药物联用的效果优于组合物或药物单独使用的效果。
具体实施方式
下面将结合实施例对本发明的实施方案进行详细描述，但是本领域技术人员将会理解， 下列实施例仅用于说明本发明，而不应视为限定本发明的范围。
实施例1：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李鲜果。
红肉苹果(洪勋1号)和樱桃李(黑果)在成熟前1个月至完全成熟时采收，采果时优先选择晴天采果，挑选并去除烂果或颜色较差的果，采后冷藏存放。获得的红肉苹果和樱桃李按照不同比例(重量比)组合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)，鲜果可供直接食用。
实施例2：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李果汁浊汁。
红肉苹果(洪勋1号)和樱桃李(黑果)采收后去籽或去核后打浆，用200目纱布过滤果汁，制得红肉苹果和樱桃李果汁浊汁。将红肉苹果和樱桃李浊汁按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备果汁。
实施例3：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李果汁清汁。
红肉苹果(洪勋1号)和樱桃李(黑果)采收后去籽或去核后打浆，用200目纱布过滤果汁，制得红肉苹果和樱桃李果汁浊汁。加果胶酶酶解过滤得清汁。将红肉苹果和樱桃李清汁按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备果汁。
实施例4：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李果酱。
红肉苹果(洪勋1号)和樱桃李(黑果)去籽或去核后打浆，水煮加热制成较稠的果酱。将红肉苹果和樱桃李果酱按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备果酱。
实施例5：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李冻干粉。
红肉苹果(洪勋1号)和樱桃李(黑果)去籽或去核后打浆，冷冻干燥制成果浆冻干粉。将红肉苹果和樱桃李冻干粉按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者先按前述不同比例混合红肉苹果和樱桃李原料，再进行打 浆制备冻干粉。
实施例6：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李压片糖果。
红肉苹果(洪勋1号)和樱桃李(黑果)去籽或去核后打浆，冷冻干燥制成果浆冻干粉，对果浆冻干粉和辅料进行压片制成压片糖果。将红肉苹果和樱桃李压片糖果按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物，或者先按前述不同比例混合红肉苹果和樱桃李原料，再进行打浆制备压片糖果。
实施例7：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李水浸提提取口服液。
(1)红肉苹果(洪勋1号)和樱桃李(黑果)去籽或去核后打浆，制得红肉苹果和樱桃李果浆。
(2)红肉苹果和樱桃李果浆按料液比1：5加水，50℃水浸提提取60min，过滤制得果浆提取液。
(3)提取液在50℃旋转蒸发浓缩，制得红肉苹果和樱桃李水浸提提取物。
(4)将提取得到的红肉苹果和樱桃李提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物。
(5)对红肉苹果和樱桃李组合提取物进行灭菌制得口服液。
实施例8：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果(红色之爱)和樱桃李(红果)水浸提提取口服液。制备步骤同实施例7。
实施例9：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果(洪勋1号)和樱桃李(黑果)醇浸提提取口服液。
参照实施例7的(1)-(5)步骤处理，其中果浆按料液比1：5加50％乙醇。醇提取物进行挥干乙醇处理。
实施例10：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李酶解超声水提取口服液。
(1)红肉苹果(洪勋1号)和樱桃李(黑果)去籽或去核后打浆，制得红肉苹果和樱桃李果浆。
(2)红肉苹果和樱桃李果浆按料液比1：5加水，添加0.5％(以果浆重量为基准)的 纤维素酶，45℃水浴提取60min，500W超声30min，过滤制得果浆提取液。
(3)提取液在50℃旋转蒸发浓缩，制得红肉苹果和樱桃李酶解超声水提取物。
(4)将提取得到的红肉苹果和樱桃李提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物。
(5)对红肉苹果和樱桃李组合提取物进行灭菌制得口服液。
实施例11：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果(洪勋3号)和樱桃李(红果)酶解超声水提取口服液。制备步骤同实施例10。
实施例12：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果(洪勋1号)和樱桃李(黑果)酶解超声醇提取口服液。
参照实施例10的(1)-(5)步骤处理，其中果浆按料液比1：5加50％。醇提取物进行挥干乙醇处理。
实施例13：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李超高压水提取口服液。
(1)红肉苹果(洪勋1号)和樱桃李(黑果)去籽或去核后打浆，制得红肉苹果和樱桃李果浆。
(2)红肉苹果和樱桃李果浆按料液比1：5加水，超高压400Mpa处理5min，过滤制得果浆提取液。
(3)提取液在50℃旋转蒸发浓缩，制得红肉苹果和樱桃李超高压水提取物。
(4)将提取得到的红肉苹果和樱桃李提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物。
(5)对红肉苹果和樱桃李组合提取物进行灭菌制得口服液。
实施例14：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果(洪勋6号)和樱桃李(红果)超高压水提取口服液。制备步骤同实施例13。
实施例15：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果(洪勋1号)和樱桃李(黑果)超高压醇提取口服液。
参照实施例13的(1)-(5)步骤处理，其中果浆按料液比1：5加50％。醇提取物 进行挥干乙醇处理。
实施例16：
本实施例所述的红肉苹果和樱桃李产品指红肉苹果和樱桃李亚临界水提取口服液。
(1)红肉苹果(洪勋1号)和樱桃李(黑果)去籽或去核后打浆，制得红肉苹果和樱桃李果浆。
(2)红肉苹果和樱桃李果浆按料液比1：5加水，亚临界萃取30min，处理温度为110℃，过滤制得果浆提取液。
(3)提取液在50℃旋转蒸发浓缩，制得红肉苹果和樱桃李亚临界水提取物。
(4)将提取得到的红肉苹果和樱桃李提取物按照不同比例(重量比)混合(1:10、1:5、1:2、1:1、2:1、5:1、10:1)制备成组合物。
(5)对红肉苹果和樱桃李组合提取物进行灭菌制得口服液。
实施例产品的降血糖效果评价：
实验例1：斑马鱼降血糖效果评价
(1)试验方法
选取胚胎发育时相为5dpf的斑马鱼幼鱼，分为模型组、对照组、阳性药组(二甲双胍)和样品组。模型组、阳性药组和样品组用葡萄糖溶液浸泡处理，并喂以高脂饲料；对照组，用系统水养殖，并饲喂高脂饲料。每天喂食幼鱼2次。阳性药物组给予二甲双胍，样品组给予待测样品。在9dpf时，收集幼鱼，研磨后加水，用血糖仪测量总组织液中的葡萄糖含量。
血糖抑制率(％)＝(模型组血糖-药物组血糖)/模型组血糖×100
(2)试验结果
试验结果如下表1所示。下表1中，单独红肉苹果组和单独樱桃李组的样品分别为实施例10步骤(3)制得的红肉苹果酶解超声水提取物和樱桃李酶解超声水提取物。红肉苹果和樱桃李组合物组的样品为实施例10步骤(4)制得的各重量比的组合物。另外，各组对应的给予浓度用单下划线示出，其中：1mg/mL或0.5mg/mL表示阳性药分散在水中的浓度；0.01％表示红肉苹果酶解超声水提取物、或者樱桃李酶解超声水提取物、或者不同重量比的由红肉苹果酶解超声水提取物和樱桃李酶解超声水提取物组成的组合物分散在水中的浓度。
之后，参照《CN104127427B一种抗癌增效组合物》和文献《姜黄素与阿霉素联合应 用抗肿瘤的协同作用》，计算相互作用系数q＝E(A+B)/(EA+(1-EA)×EB)。其中E(A+B)为两药合用的抑制率，EA和EB分别为两药单用的抑制率。q为0.85-1.15表示作用相加，q＞1.15表示作用增强，有协同作用，q＜0.85表示两药作用拮抗。计算结果如下表1所示。
表1红肉苹果和樱桃李组合物(实施例10)斑马鱼降血糖效果
Figure PCTCN2021133058-appb-000001
显著性均与模型组比较；*p＜0.05，**p＜0.01，***p＜0.001
由上表1可知，红肉苹果和樱桃李组合物(10:1-1:10)的血糖抑制率高于单独使用时的数值，计算q值均大于1.15，说明具有协同增效作用。
另外，红肉苹果和樱桃李组合物与阳性药复配使用时具有相加的作用(0.85＜q＜1.15)。组合物与阳性药的复配降血糖效果优于单独使用时的效果。与较低剂量的阳性药复配使用能较显著地提升效果。
实验例2：小鼠降血糖效果评价
(1)试验方法
取健康db/db小鼠，分为阳性药组(二甲双胍、达格列净)、模型组以及样品组；另外还设有正常对照组，正常对照组为BKS背景的C57野生型小鼠；每组20只。在适应性饲养后，模型组给予蒸馏水(0.5mL/只)，阳性药组给予二甲双胍或达格列净，样品组给予样品(0.5mL/只)，实验周期为14天。尾尖取血后用血糖仪测量小鼠血液中的葡萄糖含量。
血糖抑制率(％)＝(模型组血糖值-药物组血糖值)/模型组血糖值×100
(2)试验结果
试验结果如下表2所示。下表2中，单独红肉苹果组和单独樱桃李组的样品分别为实施例10步骤(3)制得的红肉苹果酶解超声水提取物和樱桃李酶解超声水提取物。红肉苹果和樱桃李组合物组的样品为实施例10步骤(4)制得的各重量比的组合物。另外，各组对应的给予剂量用单下划线示出。
之后，参照《CN104127427B一种抗癌增效组合物》和文献《姜黄素与阿霉素联合应用抗肿瘤的协同作用》，计算相互作用系数q＝E(A+B)/(EA+(1-EA)×EB)。其中E(A+B)为两药合用的抑制率，EA和EB分别为两药单用的抑制率。q为0.85-1.15表示作用相加，q＞1.15表示作用增强，有协同作用，q＜0.85表示两药作用拮抗。计算结果如下表2所示。
表2红肉苹果和樱桃李组合物(实施例10)小鼠降血糖效果
Figure PCTCN2021133058-appb-000002
显著性均与模型组比较；*p＜0.05，**p＜0.01，***p＜0.001
由上表1可知，红肉苹果和樱桃李组合物(10:1-1:10)的血糖抑制率高于单独使用时 的数值，计算q值均大于1.15，说明具有协同增效作用。另外，红肉苹果和樱桃李组合物与阳性药复配使用时具有相加的作用(0.85＜q＜1.15)。
以上实施例仅用以说明本发明的技术方案而非限制，对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的宗旨和范围的，其均应涵盖在本发明的保护范围之内。

Claims (10)

  1. 组合物在制备药物(如中药、中成药等)、普通食品或保健食品中的用途，所述药物(如中药、中成药等)、普通食品或保健食品用于降血糖或者用于预防和/或治疗血糖性疾病，其中，所述组合物包含：
    第一组分，所述第一组分为红肉苹果或红肉苹果提取物；和
    第二组分，所述第二组分为樱桃李或樱桃李提取物。
  2. 权利要求1的用途，其中，所述血糖性疾病选自糖尿病及糖尿病相关疾病(如I型糖尿病、II型糖尿病、糖尿病肾病等)。
  3. 权利要求1的用途，其中，所述第一组分和所述第二组分的重量比为1:10-10:1(如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，具体如1:5，1:2，1:1，2:1，5:1)。
  4. 权利要求1的用途，其中，所述红肉苹果提取物通过以下提取方式之一获得：浸提提取、酶解超声提取、超高压提取、亚临界提取或其他提取方式；
    或者，所述樱桃李提取物通过以下提取方式之一获得：浸提提取、酶解超声提取、超高压提取或亚临界提取或其他提取方式；
    或者，所述组合物是以鲜果、果汁、果酱、果粉(如冻干粉)、糖果(如压片糖果)、口服液、胶囊、片剂、果干、果脯、果酒或糕点等形式存在的。
  5. 权利要求1的用途，其中，所述红肉苹果是指果肉为红色的蔷薇科苹果属植物的果实，优选地，所述红肉苹果选自：洪勋1号(红勋1号)、洪勋3号(红勋3号)、洪勋6号(红勋6号)、夏红肉、黛红、红色之爱、Roberts Crab、红之梦、红宝石甜等；
    或者，所述樱桃李选自樱桃李红果、樱桃李黑果、樱桃李紫果、樱桃李紫黑果、樱桃李黄果等。
  6. 组合产品，其包括：
    第一产品，所述第一产品为权利要求1-5任一项所限定的组合物；
    第二产品，所述第二产品为预防和/或治疗血糖性疾病的药物。
  7. 权利要求6的组合产品，其中，所述血糖性疾病选自糖尿病及糖尿病相关疾病(如I型糖尿病、II型糖尿病、糖尿病肾病等)；
    或者，所述预防和/或治疗血糖性疾病的药物选自磺脲类药物(如格列吡嗪、格列美脲、格列齐特、格列苯脲等)、双胍类药物(二甲双胍)、α-糖苷酶抑制剂(阿卡波糖、伏格列波糖)、胰岛素增敏剂(罗格列酮、吡格列酮等)、胰岛素促泌剂(苯甲酸衍生物)，DPP-4抑制剂(沙格列汀、西格列汀等)，SGLT-2抑制剂(达格列净、恩格列净等)，胰岛素等。
  8. 权利要求6的组合产品，其中，所述第一产品和所述第二产品的重量比为20000:0.75-20000:600。
  9. 权利要求6-8任一项所述的组合产品在制备药物(如中药、中成药等)、普通食品或保健食品中的用途，所述药物(如中药、中成药等)、普通食品或保健食品用于降血糖，或者用于预防和/或治疗血糖性疾病。
  10. 权利要求9的用途，其中，所述血糖性疾病选自糖尿病及糖尿病相关疾病(如I型糖尿病、II型糖尿病、糖尿病肾病等)。
PCT/CN2021/133058 2020-11-26 2021-11-25 红肉苹果和樱桃李组合物及其在降血糖方面的应用 WO2022111570A1 (zh)

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