CN110652590A

CN110652590A - Traditional Chinese medicine compound for treating diabetes and preparation method and application thereof

Info

Publication number: CN110652590A
Application number: CN201810694184.4A
Authority: CN
Inventors: 周平; 杨宏杰; 滕宝松
Original assignee: Shanghai Fuhao Biotechnology Co Ltd
Current assignee: Shanghai Fuhao Biotechnology Co Ltd
Priority date: 2018-06-29
Filing date: 2018-06-29
Publication date: 2020-01-07
Anticipated expiration: 2038-06-29
Also published as: CN110652590B

Abstract

The invention relates to a traditional Chinese medicine compound for treating diabetes, a preparation method and application thereof. Specifically, the invention provides a composition, which is characterized by comprising raw medicinal materials or extracts thereof, wherein the raw medicinal materials comprise: (i) one or more middle-jiao and Qi tonifying medicinal materials selected from the following groups: rhizoma Polygonati, radix astragali, and radix Codonopsis; (ii) one or more liver-nourishing and spleen-invigorating medicinal materials selected from the following groups: ganoderma, Poria, and rhizoma Dioscoreae; (iii) one or more yin-nourishing and body fluid-generating medicinal materials selected from the following groups: ginseng, ophiopogon root, rehmannia root and pseudo-ginseng; and (iv) optionally one or more antipyretic antidotes selected from the group consisting of: purslane, kudzu root and scutellaria root. The composition provided by the invention can obviously reduce blood sugar, improve diabetes and/or complications and improve treatment effect.

Description

Traditional Chinese medicine compound for treating diabetes and preparation method and application thereof

Technical Field

The invention relates to the field of traditional Chinese medicines, in particular to a traditional Chinese medicine compound for treating diabetes and a preparation method and application thereof.

Background

Diabetes mellitus (diabetes mellitus) is a group of clinical syndromes caused by the interaction of genetic and environmental factors, and causes a series of metabolic disorders such as sugar, protein, fat, water and electrolytes due to absolute or relative insufficiency of insulin secretion and decreased sensitivity of target tissue cells to insulin. The clinical application of the medicine takes hyperglycemia as a common mark, a plurality of system damages can be caused by long-term illness, and acute metabolic disorders such as ketoacidosis and the like can occur when the disease condition is serious and stress occurs. The serious complications such as coronary heart disease, cerebrovascular disease, blindness, acromelic gangrene and the like in diabetes patients are obviously higher than those of non-diabetic patients. The incidence of diabetes is now on the rise year by year in both developed and developing countries. According to the statistics of the authorities, the incidence rate of diabetes in China is less than 1% from 1984, and is rapidly increased to nearly 10% nowadays.

Type 1 diabetes is absolutely deficient in insulin secretion and can only be treated with insulin replacement. However, in terms of the hypoglycemic drugs for treating type 2 diabetes clinically applied at present, various western medicines have certain limitations and adverse reactions, even serious adverse reactions, such as hypoglycemia, lactic acidosis and the like. The treatment of diabetes is always a hot spot of clinical medicine research and new drug development, and in view of that western medicine treatment usually brings great toxic and side effects to patients while obtaining curative effect, and has no advantages in the treatment of diabetic complications. So far, the traditional Chinese medicine compound formula prepared according to the traditional Chinese medicine theory has definite clinical curative effect in treating diabetes and/or complications, is easier to be accepted by patients due to higher cost performance and more convenient administration mode, has shown certain advantages and has good development prospect.

Therefore, there is a need in the art to develop a drug for treating diabetes and its complications, which can improve the therapeutic effect and reduce the pain of patients.

Disclosure of Invention

The invention aims to provide a traditional Chinese medicine compound for effectively preventing, treating and/or improving diabetes and/or complications thereof, and a preparation method and application thereof.

In a first aspect of the present invention, there is provided a composition comprising crude drug materials or extracts thereof, wherein the crude drug materials comprise:

(i) one or more middle-jiao and Qi tonifying medicinal materials selected from the following groups: rhizoma Polygonati, radix astragali, and radix Codonopsis;

(ii) one or more liver-nourishing and spleen-invigorating medicinal materials selected from the following groups: ganoderma, Poria, and rhizoma Dioscoreae;

(iii) one or more yin-nourishing and body fluid-generating medicinal materials selected from the following groups: ginseng, ophiopogon root, rehmannia root and pseudo-ginseng; and

(iv) optionally one or more heat-clearing antidotes selected from the group consisting of: purslane, kudzu root and scutellaria root.

In another preferred embodiment, the composition comprises a pharmaceutical composition, a food composition or a nutraceutical composition.

In another preferred embodiment, the composition comprises an oral formulation.

In another preferred embodiment, the composition comprises a liquid preparation or a solid preparation.

In another preferred embodiment, the pharmaceutical composition comprises (a) a pharmaceutically acceptable carrier and (b) an effective amount of the raw material or its extract.

In another preferred embodiment, the total content of the raw material herbs or extracts thereof is 0.01-99.9 wt%, preferably 1-90 wt%, more preferably 5-80 wt%, based on the weight of the composition.

In another preferred embodiment, the pharmaceutically acceptable carrier is present in an amount of 0.1 to 99.9 wt% based on the weight of the composition.

In another preferred embodiment, the extract comprises: water extract, alcohol extract, aqueous solvent extract, organic solvent extract, carbon dioxide supercritical extract or effective component, or their combination.

In another preferred embodiment, the organic solvent comprises an alcohol.

In another preferred embodiment, the alcohol comprises: C1-C6 alcohols, such as methanol, ethanol, propanol, or combinations thereof.

In another preferred embodiment, the active ingredients comprise single ingredients or mixed ingredients.

In another preferred embodiment, the ganoderma lucidum comprises a ganoderma lucidum fruiting body.

In another preferred embodiment, each gram or milliliter of the composition corresponds to 5 to 50 grams, preferably 10 to 20 grams, of the total medicinal materials, calculated on the total dry weight of the raw medicinal materials.

In another preferred embodiment, the raw material herbs comprise:

in another preferred embodiment, the heat-clearing and detoxifying medicinal material is 300-700 parts by weight.

In another preferred embodiment, the raw material herbs comprise:

in another preferred embodiment, when the composition contains a certain extract, the content of the extract is calculated according to the weight of the corresponding raw medicinal materials.

In another preferred embodiment, the raw material herbs comprise:

in another preferred embodiment, the raw material herbs comprise:

in another preferred embodiment, the raw material herbs or extracts thereof include:

(a) one or more middle-jiao and Qi tonifying medicinal materials selected from the following groups: rhizoma Polygonati, radix astragali, and radix Codonopsis;

(b) one or more liver-nourishing and spleen-invigorating medicinal materials selected from the following groups: ganoderma, Poria, and rhizoma Dioscoreae;

(c) one or more extracts of yin-nourishing and fluid-generating herbs selected from the group consisting of: ginseng extract, ophiopogon root extract, rehmannia root extract and pseudo-ginseng extract; and

(d) optionally one or more heat-clearing and detoxifying medicinal materials selected from the group consisting of: purslane, kudzu root and scutellaria root.

In another preferred embodiment, the extract of yin-nourishing and fluid-generating medicinal materials comprises saponin extract.

In another preferred embodiment, the saponin extract contains saponin substances more than or equal to 10 wt%, preferably more than or equal to 20 wt%, based on the total weight of the extract.

In another preferred embodiment, the saponin extract comprises a ginsenoside extract.

in another preferred embodiment, the raw material herbs or extracts thereof comprise:

in another preferred embodiment, the purslane is 300-700 parts by weight.

in another preferred embodiment, the ginseng extract comprises ginsenoside, preferably, the ginsenoside comprises one or more of total ginsenoside and total saponin of ginseng stems and leaves.

In another preferred embodiment, the ginseng extract is ginsenoside.

In another preferred embodiment, the ginsenoside is selected from the group consisting of: total saponins of ginseng, total saponins of ginseng stem and leaf, or a combination thereof.

In another preferred embodiment, the raw material herbs or extracts thereof include: rhizoma Polygonati extract, Ganoderma extract, ginsenoside, and optionally herba Portulacae extract.

In another preferred example, the polygonatum extract comprises polygonatum extract.

In another preferred embodiment, the ganoderma lucidum extract comprises an aqueous extract of ganoderma lucidum.

In another preferred embodiment, the water extract of ganoderma lucidum is an extract with molecular weight of 5KDa and 500KDa prepared by water extraction and alcohol precipitation.

In another preferred embodiment, the purslane extract comprises purslane extract.

In another preferred embodiment, the polygonatum sibiricum extract is prepared by the following method, comprising the steps of:

extracting rhizoma Polygonati with water, concentrating, adding organic solvent, extracting, and removing water-based organic solvent to obtain rhizoma Polygonati extract.

In another preferred example, the relative density of the polygonatum extract is 1.0-1.8.

In another preferred embodiment, the ganoderma lucidum extract is prepared by the following method, comprising the steps of:

extracting Ganoderma with water, concentrating, adding organic solvent, separating to obtain precipitate, adding water for redissolving, ultrafiltering, collecting ultrafiltrate of 500Kda-5KDa, and concentrating to obtain Ganoderma extract.

In another preferred embodiment, the relative density of the ganoderma lucidum extract is 1.0-1.80.

In another preferred embodiment, the purslane extract is prepared by a method comprising the steps of:

extracting herba Portulacae with mixed solution of organic solvent and water, and concentrating under reduced pressure to remove water-based organic solvent to obtain herba Portulacae extract.

In another preferred embodiment, the purslane extract has a relative density of 1.0-1.8.

In another preferred embodiment, the composition is in the form of tablets, capsules, granules, pills, powder, oral liquid, buccal tablets or aerosols.

In a second aspect of the invention, there is provided a process for preparing a composition according to the first aspect of the invention, said process comprising: mixing the raw materials or extracts thereof and optionally a carrier to form a composition according to the first aspect of the invention.

In another preferred embodiment, the carrier is a pharmaceutically acceptable carrier, a food acceptable carrier, or a health product acceptable carrier.

In a third aspect of the present invention, there is provided a use of the composition according to the first aspect of the present invention for the preparation of a medicament for the prevention, treatment and/or amelioration of diabetes and/or diabetic complications.

In another preferred embodiment, the diabetes is selected from the group consisting of: type I diabetes, type II diabetes, occult diabetes, and gestational diabetes.

In another preferred embodiment, the diabetic complication is selected from the group consisting of: diabetic nephropathy, diabetic ocular complications, diabetic foot, diabetic cardiovascular complications, and diabetic neuropathy.

In a fourth aspect of the invention, there is provided a method for the prevention, treatment and/or amelioration of diabetes and/or diabetic complications by administering to a subject in need thereof a composition according to the first aspect of the invention.

In another preferred embodiment, the subject comprises a human or non-human mammal.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Detailed Description

The inventor of the present invention has made extensive and intensive studies and has unexpectedly found a composition for preventing and/or treating diabetes and/or diabetic complications, based on the theories associated with the traditional Chinese medicine. The inventor selects raw medicinal materials to prepare the traditional Chinese medicine composition for preventing and/or treating diabetes and/or complications. Experiments show that the composition prepared by mixing the extracts of rhizoma polygonati, lucid ganoderma and purslane and the ginsenoside not only has the functions of obviously reducing blood sugar and regulating blood sugar, but also can assist in treating diabetes, relieve complications generated by the diabetes and improve the immunity of the organism. On the basis of this, the present invention has been completed.

Term(s) for

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, the terms "comprises," "comprising," "includes," "including," and "including" are used interchangeably and include not only closed-form definitions, but also semi-closed and open-form definitions. In other words, the term includes "consisting of … …", "consisting essentially of … …".

As used herein, the term "optionally" refers to optional or not.

As used herein, the term "relative density" refers to the ratio of the density of a substance to the density of a reference substance, in the present invention, the density of water at 4 ℃ (used as 1), to the density of another substance (such as polygonatum sibiricum extract, purslane extract or ganoderma lucidum extract) to the density of water at 4 ℃ (each specified condition).

As used herein, the term "pharmaceutically acceptable carrier" ingredient refers to a substance that is suitable for use in humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response), i.e., at a reasonable benefit/risk ratio.

The term "effective amount," as used herein, refers to an amount that produces a function or activity in and is acceptable to humans and/or animals. It will be understood by those skilled in the art that the "effective amount" may vary depending on the form of the pharmaceutical composition, the severity of the disease, and the combination with other drugs.

"preventing", "treating" or "ameliorating" as used herein includes delaying and stopping the progression of the disease, or eliminating the disease, and does not require 100% inhibition, elimination or reversal. In some embodiments, the compositions or pharmaceutical compositions of the invention are capable of preventing the development of diabetes and/or diabetic complications, or reducing, inhibiting and/or reversing existing diabetes and/or diabetic complications by, e.g., at least about 10%, at least about 30%, at least about 50%, or at least about 80%, as compared to the levels observed in the absence of the compositions or pharmaceutical compositions of the invention.

As used herein, the terms "parts by weight" and "parts by weight" are used interchangeably and can be any fixed weight expressed in milligrams, grams, or kilograms (e.g., 1mg, 1g, 2g, or 1kg, etc.). For example, a composition consisting of 1 part by weight of component a and 9 parts by weight of component b may be a composition consisting of 1g of component a +9 g of component b, or 10 g of component a +90 g of component b. In the composition, the percentage content of a certain component is (part by weight of the component/sum of parts by weight of all components) × 100%, and thus, in a composition composed of 1 part by weight of component a and 9 parts by weight of component b, the content of component a is 10% and the content of component b is 90%.

As used herein, the term "crude drug material" refers to a traditional Chinese medicinal material that is an active drug material in the compositions of the present invention, which can include various forms, for example, including but not limited to dry, fresh, crude, cooked, processed, or combinations thereof. In addition, when the composition of the present invention contains a certain crude drug extract, the term also includes the crude drug corresponding to the crude drug extract or the corresponding crude drug used to prepare the extract.

In the invention, the main raw medicinal materials have the following properties and main effects:

middle-jiao and qi tonifying medicinal material

Rhizoma Polygonati (Polygonatum sibiricum)

Rhizoma Polygonati is dried rhizome of Polygonatum kingianum, Polygonatum sibiricum Red, Polygonatum cyrtonema Hua et Zucc. Sweet in flavor and neutral in nature, and entering spleen, lung and kidney meridians. Huang Jing tonifies middle-jiao and Qi, moistens heart and lung, strengthens tendons and bones, and "Ri Hua Zi Ben Cao" says "tonifying five kinds of fatigue and seven kinds of injuries, assisting tendons and bones, stopping hunger, and resisting cold and summer heat. Tonify spleen and stomach, moisten heart and lung.

In the present invention, when the polygonatum sibiricum extract is used, the corresponding water extract, alcohol extract, CO2 supercritical extract, aqueous solvent extract, or a combination thereof is preferably used. In the present invention, as for the polygonatum sibiricum extract, an extract containing or rich in steroidal saponins is particularly suitable for use in the composition of the present invention. Typically, in the Polygonatum sibiricum extract, the content of steroidal saponins is usually not less than 1 wt%, preferably not less than 5 wt%, based on the total weight of the extract.

Astragalus membranaceus (Fisch.) Bunge.)

Radix astragali is root of Astragalus membranaceus bge of Leguminosae. Warm in nature and sweet in taste. Tonify qi, strengthen superficies, remove toxicity, expel pus, induce diuresis, and promote granulation. Can be used for treating asthenia due to qi deficiency, chronic diarrhea, rectocele, chronic nephritis, albuminuria, diabetes, etc.

In the present invention, when the extract of astragalus membranaceus is used, the corresponding aqueous extract, alcoholic extract, CO2 supercritical extract, aqueous solvent extract, or combination thereof is preferably used. In the present invention, as for the extract of astragalus, an extract containing or enriched in saponins and/or flavones is particularly suitable for use in the composition of the present invention. Typically, the content of saponins and/or flavones in the extract of Astragalus membranaceus is usually > 1 wt%, preferably > 5 wt%, based on the total weight of the extract.

Codonopsis pilosula (Franch.) Nannf.)

The radix Codonopsis is dried root of radix Codonopsis, radix Codonopsis Lanceolatae or radix Codonopsis Pilosulae of Campanulaceae. Sweet in flavor and neutral in nature. Has the effects of invigorating spleen and replenishing qi, quenching thirst, invigorating spleen and benefiting lung, nourishing blood and promoting fluid production. Can be used for treating deficiency of spleen-qi and lung-qi, anorexia, listlessness, cough, asthma, thirst due to body fluid consumption, and diabetes due to internal heat.

In the present invention, when using the Codonopsis pilosula extract, the corresponding aqueous extract, alcoholic extract, CO2 supercritical extract, aqueous solvent extract, or combination thereof is preferably used. In the present invention, as regards the Codonopsis pilosula extract, sterol-containing or sterol-rich extracts are particularly suitable for use in the present compositions. Typically, in Codonopsis pilosula extract, sterols are usually present in an amount of at least 1 wt%, preferably at least 5 wt%, based on the total weight of the extract.

Liver-nourishing spleen-invigorating medicinal material

Ganoderma lucidum (Ganoderma lucidum (leys. ex Fr.) Karst.)

Ganoderma is also called Linzhongling and Qiongzhen and is the fruiting body of Ganoderma lucidum of Polyporaceae. Ganoderma lucidum is sweet and bitter in taste and neutral in nature, and has effects of nourishing heart, tranquilizing mind, calming lung, invigorating qi, regulating qi-flowing for removing blood stasis, nourishing liver and invigorating spleen, and can be recorded in Shen nong Ben Cao Jing for tranquilizing mind, strengthening tendons and bones, reducing weight, and prolonging life. Modern pharmacological research proves that the ganoderma lucidum has the effects of protecting liver, regulating immunity and the like.

In the present invention, when the Ganoderma extract is used, the corresponding water extract, alcohol extract, CO are preferably used₂A supercritical extract, an aqueous solvent extract, or a combination thereof. In the present invention, the extract of Ganoderma lucidum contains or is rich in polysaccharides, proteins, sterols and/or triterpenesExtracts are particularly suitable for use in the compositions of the present invention. Typically, in the Ganoderma extract, the sterol content is usually ≥ 1 wt%, preferably ≥ 5 wt%, based on the total weight of the extract.

Poria cocos (Poria cos (Schw.) -Wolf)

Poria is dried sclerotium of Poria cocos (Schw.) wolf of Polyporaceae. Sweet and bland in flavor and mild in nature. It enters heart, lung, spleen and kidney meridians. Has the effects of promoting diuresis, eliminating dampness, invigorating spleen, and calming heart.

In the present invention, when the poria cocos wolf extract is used, the corresponding water extract, alcohol extract, CO2 supercritical extract, aqueous solvent extract, or combination thereof is preferably used. In the present invention, as for the extract of poria cocos wolf, an extract containing or enriched in polysaccharides, triterpenes and/or sterols is particularly suitable for use in the composition of the invention. Typically, in the Poria extract, sterols are usually contained in an amount of 1 wt% or more, preferably 5 wt% or more, based on the total weight of the extract.

Chinese yam (Dioscorea opposita)

The rhizoma Dioscoreae is dried rhizome of Dioscorea opposita Thunb of Dioscoreaceae. Rhizoma Dioscoreae has effects of nourishing yin, strengthening body constitution, promoting digestion, astringing sweating due to deficiency, and relieving diarrhea, and can be used for treating spleen deficiency diarrhea, lung deficiency cough, diabetes, and frequent micturition.

In the present invention, when yam extract is used, the corresponding aqueous extract, alcoholic extract, CO2 supercritical extract, aqueous solvent extract, or combination thereof is preferably used. In the present invention, as for the yam extract, polysaccharide-containing or polysaccharide-rich extracts are particularly suitable for use in the present composition. Typically, sterols are generally present in yam extract at levels of greater than or equal to 1 wt%, preferably greater than or equal to 5 wt%, based on total weight of the extract.

Medicinal materials for nourishing yin and promoting production of body fluid

Ginseng (Panax ginseng C.A.Mey.)

The Ginseng radix is dried root of Panax ginseng C.A. Meyer of Araliaceae. Ginseng is sweet, slightly bitter and slightly warm, enters spleen and lung meridians, has sweet taste, can nourish yin, invigorate yang when warm, can benefit spleen qi, transport and transform essence, and transform yin fluid, is a good product for strengthening yang and nourishing yin, and is a first choice medicine for thirst quenching and thirst quenching. The book Ben Cao Hui Yan says: ginseng, radix Ginseng, has the effects of invigorating qi, promoting blood circulation, and nourishing essence and spirit. Modern pharmacological research proves that ginseng has a bidirectional regulating effect on the central nervous system, has a direct effect on cardiac muscles and blood vessels, and has a certain treatment effect on different types of neurasthenia patients.

In the present invention, when the ginseng extract is used, the corresponding aqueous extract, alcoholic extract, CO2 supercritical extract, aqueous solvent extract, or combination thereof is preferably used. In the present invention, for ginseng extracts, saponin-containing or saponin-rich extracts are particularly suitable for use in the present compositions. Typically, in ginseng extracts, sterols are usually present in amounts of ≥ 1 wt%, preferably ≥ 5 wt%, based on the total weight of the extract.

Radix Ophiopogonis (Ophiogon japonicus (Linn.f.) Ker-Gawl.)

Radix Ophiopogonis is dried root tuber of Ophiopogon japonicus of Ophiopogon of Liliaceae. Sweet, slightly bitter and slightly cold in taste. It enters heart, lung and stomach meridians. Nourishing yin and promoting fluid production, moistening lung and arresting cough, and can be used for treating deficiency of fluid and thirst due to lung-stomach yin deficiency, dry cough and hemoptysis; palpitation due to heart yin deficiency and fluid impairment due to heat in the late stage of fever.

In the present invention, when using the ophiopogon japonicus extract, the corresponding water extract, alcohol extract, CO2 supercritical extract, aqueous solvent extract, or a combination thereof is preferably used. In the present invention, for extracts of Opiophogon japonicus, extracts containing or enriched in steroidal saponins, sterols, and/or polysaccharides are particularly suitable for use in the compositions of the present invention. Typically, in the Ophiopogon japonicus extract, sterols are usually contained in an amount of 1 wt% or more, preferably 5 wt% or more, based on the total weight of the extract.

Rehmannia (Rehmannia glutinosa (Gaetn.) Libosch.ex Fisch.et Mey.)

Fresh or dried root tuber of rehmannia glutinosa Libosch of Scrophulariaceae family. Is divided into fresh rehmannia root, dry rehmannia root and prepared rehmannia root. Fresh rehmannia; clear heat and promote fluid production, cool blood and stop bleeding. Gan Di Huang can clear heat and cool blood, nourish yin and promote fluid production. Prepared rehmannia root, radix rehmanniae Praeparata has the effects of enriching blood, nourishing yin, replenishing vital essence and replenishing marrow.

In the present invention, when the rehmannia glutinosa extract is used, the corresponding water extract, alcohol extract, CO2 supercritical extract, aqueous solvent extract, or a combination thereof is preferably used. In the present invention, for rehmannia glutinosa extract, extracts containing or enriched in glycosides are particularly suitable for use in the present composition. Typically, in the rehmannia glutinosa extract, sterols are usually contained in an amount of 1 wt% or more, preferably 5 wt% or more, based on the total weight of the extract.

Notoginseng radix (Panax notogeng (Burk.) F.H.Chen)

Notoginseng radix is the dried root and rhizome of Panax notoginseng belonging to Araliaceae, and has effects of nourishing yin, promoting fluid production, and dispelling blood.

In the present invention, when the notoginseng extract is used, the corresponding water extract, alcohol extract, CO2 supercritical extract, aqueous solvent extract, or a combination thereof is preferably used. In the present invention, for pseudo-ginseng extract, saponin-containing or saponin-rich extract is particularly suitable for use in the present composition. Typically, sterols are usually present in the notoginseng extract in an amount of more than or equal to 1 wt%, preferably more than or equal to 5 wt%, based on the total weight of the extract.

Clearing away heat and toxic material

Purslane (Portulaca oleracea L.)

Herba Portulacae is whole plant of herba Portulacae of Portulacaceae of Caryophyllales. Purslane is cold in nature and sweet and sour in taste, enters heart, liver, spleen and large intestine channels, can clear away heat and toxic materials, dispel blood and reduce swelling, and has thirst quenching effect recorded in Kaibao Bencao.

In the present invention, when purslane extract is used, the corresponding aqueous extract, alcoholic extract, CO2 supercritical extract, aqueous solvent extract, or combination thereof is preferably used. In the present invention, for purslane extracts, extracts containing or enriched in organic acids and/or alkaloids are particularly suitable for use in the present compositions. Typically, in the purslane extract, sterols are generally present in an amount of at least 1 wt%, preferably at least 5 wt%, based on the total weight of the extract

Radix Puerariae (Pueraria Lobatae Radix)

Pueraria lobata (Willd.) Ohwi is dry root of Pueraria lobata Ohwi of Leguminosae, and is called as Pueraria lobata Ohwi. Collected in autumn and winter, cut into thick slices or small blocks when fresh, and dried. Sweet, pungent and cool. Has the functions of expelling pathogenic factors from muscles, allaying fever, promoting eruption, promoting the production of body fluid to quench thirst, invigorating yang and stopping diarrhea. It is commonly indicated for exterior syndrome with fever, stiffness and pain of neck and back, measles without adequate eruption, thirst due to fever, diabetes due to yin deficiency, dysentery due to heat-purging and diarrhea due to spleen deficiency.

In the present invention, when the puerariae radix extract is used, the corresponding water extract, alcohol extract, CO2 supercritical extract, aqueous solvent extract, or a combination thereof is preferably used. In the present invention, for the pueraria root extract, an extract containing or enriched in glycosides and/or ketones is particularly suitable for use in the composition of the present invention. Typically, in the kudzu root extract, the sterol content is usually not less than 1 wt%, preferably not less than 5 wt%, based on the total weight of the extract

Scutellaria baicalensis (Scutellaria baicailensis Georgi)

Scutellariae radix is root of Scutellariae radix of Scutellaria of Labiatae of Capillales. Is bitter in taste and cold in nature, and has the effects of clearing heat and drying dampness, purging fire and removing toxicity, stopping bleeding, preventing miscarriage and the like. Can be used for treating epidemic febrile disease, upper respiratory infection, cough due to lung heat, yellow gallbladder due to damp-heat, pneumonia, dysentery, hemoptysis, conjunctival congestion, threatened abortion, and hypertension.

In the present invention, when the scutellaria baicalensis extract is used, the corresponding aqueous extract, alcoholic extract, CO2 supercritical extract, aqueous solvent extract, or combination thereof is preferably used. In the present invention, for scutellaria baicalensis extracts, extracts containing or enriched in flavones and/or glycosides are particularly suitable for use in the compositions of the present invention. Typically, in the Scutellariae radix extract, sterol content is usually not less than 1 wt%, preferably not less than 5 wt%, based on the total weight of the extract

Composition comprising a metal oxide and a metal oxide

The present invention provides a composition useful for preventing, treating and/or ameliorating diabetes and/or complications thereof.

Compositions of the present invention include, but are not limited to: the medicine composition, the food composition or the health-care product composition only contains one or more medicinal materials of rhizoma polygonati, astragalus, codonopsis pilosula, lucid ganoderma, poria cocos, Chinese yam, ginseng, radix ophiopogonis, rehmannia, pseudo-ginseng, purslane, radix puerariae and scutellaria baicalensis or extracts thereof; or substantially comprises one or more of rhizoma Polygonati, radix astragali, radix Codonopsis, Ganoderma, Poria, rhizoma Dioscoreae, Ginseng radix, radix Ophiopogonis, rehmanniae radix, Notoginseng radix, herba Portulacae, radix Puerariae, and Scutellariae radix or their extracts. In the composition, the content of the raw medicinal materials or the extracts thereof can be 0.1 to 99.9wt percent based on the weight of the composition. The composition can also contain a pharmaceutically, food or health-care product acceptable carrier.

In the raw material medicaments, (i) sealwort, astragalus and codonopsis pilosula belong to middle-jiao and qi-tonifying medicaments; (ii) the lucid ganoderma, the tuckahoe and the yam belong to the medicines for nourishing the liver and strengthening the spleen; (iii) ginseng, dwarf lilyturf tuber, rehmannia root and pseudo-ginseng belong to yin-nourishing and body fluid-generating medicaments; (iv) purslane, kudzu root and scutellaria root belong to heat-clearing and detoxifying drugs.

In the present invention, it should be understood that the extract not only includes a concentrated solution (e.g. extract) or an effective component (e.g. powder) obtained by extracting raw material herbs after mixing, but also includes a concentrated solution (e.g. extract) or a mixture of effective components (including a mixture between the concentrated solution and the concentrated solution, between the effective component and the effective component, or between the concentrated solution and the effective component) obtained by extracting a single herb from the raw material herbs. The active ingredients of the raw medicinal materials comprise single ingredients or mixed ingredients.

In a preferred embodiment of the present invention, in the composition of the present invention, the raw material or the extract thereof includes one or more of polygonatum sibiricum, ganoderma lucidum, ginsenoside and purslane.

Ginsenoside is an important component of ginseng extract, and can be present in different parts of ginseng, such as root, stem and leaf, and the like, and can comprise total ginsenoside, total saponin of ginseng stem and leaf, total saponin of ginseng bud and the like according to the different existing parts. For example, the total saponins of ginseng are the total saponins obtained by processing the dried root and rhizome of ginseng. The total saponin of caulis Et folium Ginseng is obtained by processing dried caulis Et folium Ginseng. Typically, the ginsenoside comprises one or more of total saponins of ginseng and total saponins of ginseng stem and leaf.

In a preferred embodiment of the present invention, the amounts of the raw materials used for preparing the composition of the present invention are shown in table 1:

TABLE 1

Middle-jiao and qi tonifying medicinal material	500-1500 parts by weight:
		liver-nourishing spleen-invigorating medicinal material	100-500 parts by weight;
medicinal materials for nourishing yin and promoting production of body fluid	100-500 parts by weight; and
		heat-clearing and detoxifying medicinal material	0 to 1000 parts by weight.

As a preferred mode of the present invention, the raw material herbs or extracts thereof may include: rhizoma Polygonati, Ganoderma, Ginseng radix and herba Portulacae. More preferably, the dosages of rhizoma polygonati, ganoderma lucidum, ginseng and purslane are shown in table 2:

TABLE 2

Rhizome of Siberian solomonseal	500-1500 parts by weight:
		glossy ganoderma	100-500 parts by weight;
ginseng radix	100-500 parts by weight; and
		herba Portulacae	300-700 parts by weight.

In a preferred embodiment of the present invention, the composition of the present invention comprises the following raw medicinal materials or extracts thereof:

(c) one or more extracts of yin-nourishing and salivation-promoting herbs selected from: ginseng extract, ophiopogon root extract, rehmannia root extract and pseudo-ginseng extract; and

(d) optionally one or more heat-clearing and detoxifying medicinal materials selected from the group consisting of: herba Portulacae, radix Puerariae, and Scutellariae radix;

as a preferred mode of the present invention, the amounts of the raw materials or extracts thereof used for preparing the composition of the present invention are shown in Table 3:

TABLE 3

As a preferred mode of the present invention, the raw material herbs or extracts thereof may include: rhizoma Polygonati, Ganoderma, Ginseng radix extract and herba Portulacae. More preferably, the rhizoma polygonati, ganoderma lucidum, ginseng extract and purslane are used in the amounts shown in table 4:

TABLE 4

Rhizome of Siberian solomonseal	500-1500 parts by weight:
		glossy ganoderma	100-500 parts by weight;
ginseng extract	10-50 parts by weight; and
		herba Portulacae	0 to 1000 parts by weight.

As another preferred mode of the present invention, the raw material herbs or extracts thereof may include: rhizoma Polygonati, Ganoderma, ginsenoside, and optionally herba Portulacae. More preferably, the amounts of polygonatum, ganoderma lucidum, ginsenoside and optionally purslane are as shown in table 5:

TABLE 5

Rhizome of Siberian solomonseal	600-1200 parts by weight:
		glossy ganoderma	200-400 parts by weight;
ginsenoside	15-40 parts by weight; and
		herba Portulacae	300-700 parts by weight.

In another preferred mode, the raw material herbs or extracts thereof include: rhizoma Polygonati extract, Ganoderma extract, ginsenoside, and optionally herba Portulacae extract.

As a preferred embodiment of the present invention, in the prepared composition, the polygonatum sibiricum, the ganoderma lucidum and optionally the purslane are respectively extracted to respectively obtain extracts containing effective components, and then the polygonatum sibiricum extract, the ganoderma lucidum extract and optionally the purslane extract are mixed with the ginsenoside and the carrier to obtain the composition of the present invention.

The dosage form of the composition of the present invention is not particularly limited, and may be any dosage form suitable for mammals. Preferably, the dosage form may comprise tablets, capsules, granules, pills, powders, oral liquids, buccal tablets, or aerosols. The preferred composition is a solid composition from the standpoint of ease of preparation, administration or administration. Oral administration is preferred.

The composition of the present invention may be added with various conventional carriers and/or adjuvants required for preparing different dosage forms, such as filler (e.g. starch, cellulose, dextrin), disintegrant (sodium carboxymethyl starch), lubricant (magnesium stearate), solvent (purified water), cosolvent (ethanol), and coating material. Can be prepared into any common dosage form such as tablet, capsule, granule, capsule, pill, and powder by conventional method.

Examples of pharmaceutically acceptable carrier moieties are cellulose and its derivatives (e.g., methylcellulose, ethylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, etc.), gelatin, talc, solid lubricants (e.g., stearic acid, magnesium stearate), calcium sulfate, vegetable oils (e.g., soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (e.g., propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifiers (e.g., tween), wetting agents (e.g., sodium lauryl sulfate), buffers, chelating agents, thickeners, pH adjusters, transdermal enhancers, colorants, flavors, stabilizers, antioxidants, preservatives, bacteriostats, pyrogen-free water, etc.

In addition, in a preferred mode, each gram or each milliliter of the composition corresponds to 5 to 50 grams, preferably 10 to 20 grams of the total medicinal materials calculated by the total dry weight of the raw medicinal materials.

Preparation method

After obtaining the raw materials or their extracts and their formulations for the composition of the present invention, those skilled in the art can process the raw materials or their extracts into drugs by conventional methods. Such processing includes, but is not limited to: pulverizing, extracting with water, extracting with aqueous solvent, extracting with organic solvent, extracting with supercritical carbon dioxide or sequentially extracting with multiple different solvents.

After being mixed, the raw medicinal materials can be extracted by a proper method to obtain effective components (namely extracts of the medicinal materials), and the effective components are mixed with a carrier to prepare the composition; in addition, each raw material medicine can also be respectively extracted (for example, the same or different extraction or processing methods are respectively adopted) to obtain effective components (namely, extracts of the medicinal materials), and the effective components are combined and mixed with a carrier to prepare the composition of the invention. It should be understood that the active ingredients obtained by extraction may exist in various forms, such as single or mixed pure active ingredient powder obtained by extracting and purifying raw material herbs, or extract obtained by extracting and concentrating raw material herbs with solvent (the active ingredients exist in the extract), or other forms.

In a preferred embodiment, the raw materials can be directly added into the composition or added into the composition after being crushed.

In addition, those skilled in the art can also directly process (such as crushing, extracting and the like) the effective parts of the raw medicinal materials to prepare the composition of the invention. In addition, those skilled in the art can extract effective components from each of the raw materials and mix them to prepare the composition of the present invention.

In a preferred embodiment of the present invention, the composition of the present invention is prepared by mixing the extracts of the raw medicinal materials with a carrier, wherein the extracts of the raw medicinal materials are mixed.

In another preferred embodiment of the present invention, the raw material herbs or extracts thereof include: rhizoma Polygonati extract, Ganoderma extract, ginsenoside, and optionally herba Portulacae extract.

In another preferred embodiment, the purslane extract comprises an ethanol extract.

Preferably, the polygonatum extract, the ganoderma lucidum extract and the purslane extract can be prepared by the following methods:

polygonatum sibiricum extract

Extracting rhizoma Polygonati with water, concentrating, adding organic solvent, extracting, and removing organic solvent to obtain rhizoma Polygonati extract.

In another preferred embodiment, the organic solvent is an alcohol. Typically, the alcohol includes, but is not limited to, C1-C6 alcohols, such as methanol, ethanol, propanol, or combinations thereof.

In the preparation process of the rhizoma polygonati extract, when the rhizoma polygonati extract is extracted by water, effective components can be effectively extracted by multiple times of extraction, and the frequency of the water extraction is preferably 1-5 times. In the case of multiple extractions with water, the time for each extraction is preferably 0.5 to 4 hours. In a preferred embodiment, the aqueous extract is concentrated to obtain an extract (the relative density of the extract is 1.0-1.60, preferably 1.0-1.40 at 60 ℃) before the organic solvent is added for extraction. In another preferred embodiment, the content of the organic solvent is 50 to 80 wt% after the organic solvent is added. In another preferred example, the relative density of the polygonatum extract is 1.0-1.80, preferably 1.0-1.50.

Ganoderma lucidum extract

Extracting Ganoderma with water, concentrating, adding organic solvent, separating to obtain precipitate, adding water for redissolving, ultrafiltering, collecting ultrafiltrate of 500Kda-5KDa, and concentrating to obtain Ganoderma extract (Ganoderma extract).

In the preparation process of the ganoderma lucidum extract, when water is firstly used for extraction, effective components can be effectively extracted by multiple times of extraction, and the time of water extraction is preferably 1-5 times. In the case of multiple extractions with water, the time for each extraction is preferably 0.5 to 4 hours. In a preferred embodiment, the aqueous extract is concentrated to obtain an aqueous extract (the relative density of the extract is 1.0-1.60, preferably 1.0-1.40 at 60 ℃) before the organic solvent is added for extraction. In another preferred example, the weight of the added organic solvent is 1-6 times of that of the water extract.

In another preferred embodiment, the relative density of the ganoderma lucidum extract is 1.0-1.80, preferably 1.0-1.60.

Purslane extract

Extracting herba Portulacae with mixed solution of organic solvent and water, concentrating under reduced pressure to remove organic solvent to obtain herba Portulacae extract (herba Portulacae)

In a preferred embodiment, the content of the organic solvent in the mixed solution of the organic solvent and water is 40 to 80 wt%, preferably 50 to 80 wt%.

In another preferred example, the number of times of extraction of the mixture of the organic solvent and water is 1 to 6.

In another preferred embodiment, the time of each extraction of the mixture of the organic solvent and water is 0.5 to 4 hours.

In another preferred embodiment, the purslane extract has a relative density of 1.0-1.80, preferably 1.0-1.60.

Use, mode of administration and method of treatment

The composition of the invention can be directly used for preparing medicines for preventing and/or treating diabetes and/or diabetic complications. The composition of the present invention may also contain other optional medicinal materials or extracts thereof or other drugs effective for the treatment and/or prevention of diabetes and/or diabetic complications.

The compositions of the invention are generally administered daily in a dosage of 0.001 to 20g/kg of animal body weight, preferably 1 to 4 divided doses per day, or in sustained release form. For most mammals, the total daily dose is 0.05-600 g. The particular dosage will, of course, vary with the mode of administration, the dosage form, and the severity of the condition being treated, and is within the skill of the skilled practitioner. Administration may be by conventional routes including (but not limited to): oral, intramuscular, dermal, or topical administration. Oral administration is preferred.

The present invention also provides a method for preventing and/or treating diabetes and/or diabetic complications, the method comprising the steps of: the compositions of the present invention are administered to a subject in need thereof. The subject may be a human or non-human mammal (e.g., dog, pig, cat, monkey, sheep, horse, cow, etc.).

The main advantages of the invention include:

1. the traditional Chinese herbal medicines with the ancient prescription are preferably selected as middle-jiao and Qi tonifying medicines, liver nourishing and spleen strengthening medicines and yin nourishing and body fluid generating medicines for scientific compatibility, and the novel prescription has obvious blood sugar reducing effect and can prevent, treat and/or improve diabetes and/or diabetic complications.

2. The compound basic medicinal materials comprise rhizoma polygonati, purslane, lucid ganoderma and ginseng, wherein the medicinal materials in the compound are listed in a list of traditional Chinese medicinal materials issued by the national health and life-counting committee, which are both food and medicines, and the safety of the compound is widely accepted.

3. The compound basic medicinal materials comprise rhizoma polygonati, purslane, lucid ganoderma and ginseng, and have reasonable compatibility and no incompatibility.

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.

EXAMPLE 1 preparation of powder 1

1.1 formulation 1:

1200 parts of rhizoma polygonati, 600 parts of purslane, 400 parts of lucid ganoderma fruit body and 40 parts of ginseng total saponin;

wherein the total ginsenoside is a commercial product (the content of the total ginsenoside is more than or equal to 90 percent), and 40 weight parts of the total ginsenoside is equivalent to 330 weight parts of ginseng medicinal material.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

1200 parts of rhizoma polygonati, 600 parts of purslane and 400 parts of lucid ganoderma sporocarp by weight are cleaned, washed, sterilized, dried and crushed by a crusher.

(b) Preparation of the extract

1200 parts by weight of rhizoma polygonati are added with water and decocted and extracted for 2 times, each time lasts for 2 hours, and the water extract is filtered and then concentrated under reduced pressure to form an extract with the relative density of 1.20(60 ℃). Adding ethanol until the ethanol content reaches 65 wt%, fine extracting, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C).

Extracting 600 weight parts of purslane with 50% ethanol under reflux for 2 times, and concentrating the ethanol extract under reduced pressure to obtain purslane extract with relative density of 1.30(60 deg.C) each time for 2 hours to obtain the purslane extract.

Decocting 400 parts by weight of ganoderma lucidum fruiting body with water for 2 times, each time for 2 hours, filtering the water extract, concentrating the filtrate under reduced pressure to a concentrated solution with the relative density of 1.10(60 ℃), adding 3 times of ethanol for alcohol precipitation and standing for 12 hours, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the aqueous solution with ultrafiltration membranes with the molecular weight grades of 500KDa and 5KDa in sequence, concentrating the ultrafiltrate in the middle parts of 5KDa and 500KDa under reduced pressure to ganoderma lucidum extract with the relative density of 1.30(60 ℃), and obtaining the ganoderma lucidum extract.

1.3 preparation of powder 1

Mixing Ginseng radix total saponin, the above prepared rhizoma Polygonati extract, herba Portulacae extract and Ganoderma extract with appropriate amount of sodium carboxymethyl starch, dextrin and purified water, stirring, drying into fine powder, and sieving to obtain powder.

EXAMPLE 2 preparation of powder 2

1.1 formulation 1:

1200 parts of rhizoma polygonati, 600 parts of purslane, 400 parts of lucid ganoderma fruit bodies and 40 parts of ginseng stem leaf total saponins;

wherein, the ginseng stem and leaf total saponins are purchased from the market (the content of the ginseng stem and leaf total saponins is more than or equal to 90 percent), and 40 weight parts of the ginseng stem and leaf total saponins are equivalent to 400 weight parts of ginseng medicinal materials.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

(b) Preparation of the extract

Decocting 1200 weight parts of rhizoma polygonati with water for 3 times, each time for 1 hour, filtering the water extract, concentrating under reduced pressure to obtain an extract with the relative density of 1.20(60 ℃), adding ethanol until the content of the ethanol reaches 65 wt%, carrying out fine extraction, and concentrating under reduced pressure to obtain the rhizoma polygonati extract with the relative density of 1.30(60 ℃), thus obtaining the rhizoma polygonati extract.

Extracting herba Portulacae 600 weight parts with 60% ethanol under reflux for 3 times, each time for 1 hr, and concentrating the ethanol extractive solution under reduced pressure to obtain herba Portulacae extract with relative density of 1.25(60 deg.C).

Decocting 400 parts by weight of ganoderma lucidum fruiting body with water for 3 times, each time for 1 hour, filtering the water extract, concentrating the filtrate under reduced pressure to a concentrated solution with the relative density of 1.10(60 ℃), adding 3 times of ethanol for alcohol precipitation and standing for 24 hours, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the water solution with ultrafiltration membranes with the molecular weight grades of 500KDa and 5KDa in sequence, concentrating the ultrafiltrate in the middle parts of 5KDa and 500KDa under reduced pressure to obtain ganoderma lucidum extract with the relative density of 1.30(60 ℃), and obtaining the ganoderma lucidum extract.

1.3 preparation of powder 2

Mixing caulis Et folium Ginseng total saponin, rhizoma Polygonati extract, herba Portulacae extract, Ganoderma extract, appropriate amount of sodium carboxymethyl starch, dextrin, and purified water, stirring, drying into fine powder, and sieving to obtain powder.

Example 3 preparation of granule 1

1.1 formulation 1:

600 parts of sealwort, 300 parts of purslane, 200 parts of lucid ganoderma sporocarp and 20 parts of ginseng stem and leaf total saponin;

wherein, the ginseng stem and leaf total saponins are purchased from the market (the content of the ginseng stem and leaf total saponins is more than or equal to 90 percent), and 20 weight parts of the ginseng stem and leaf total saponins are equivalent to 200 weight parts of ginseng medicinal materials.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

The preparation method comprises the following steps of cleaning, washing, sterilizing and drying 600 parts by weight of rhizoma polygonati, 300 parts by weight of purslane and 200 parts by weight of lucid ganoderma sporocarp, and crushing by a crusher.

(b) Preparation of the extract

Decocting 600 weight parts of rhizoma Polygonati in water for 2 times, each time for 2 hours, filtering the water extract, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, fine extracting, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C).

300 parts by weight of purslane is extracted by 50 percent ethanol under reflux for 2 times, each time lasts for 2 hours, and the ethanol extract is decompressed and concentrated into purslane extract with the relative density of 1.30(60 ℃), thus obtaining the purslane extract.

Decocting Ganoderma encarpium 200 weight parts in water for 2 times, each for 2 hr, filtering the water extract, concentrating the filtrate under reduced pressure to obtain concentrated solution with relative density of 1.10(60 deg.C), adding 3 times of ethanol, precipitating with ethanol, standing for 12 hr, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the water solution with ultrafiltration membranes of 500KDa and 5KDa molecular weight grades, concentrating the ultrafiltrate in the middle part of 5KDa and 500KDa under reduced pressure to obtain Ganoderma extract with relative density of 1.30(60 deg.C), and obtaining Ganoderma extract.

1.3 preparation of granules 1

Mixing caulis Et folium Ginseng total saponin, rhizoma Polygonati extract, herba Portulacae extract, Ganoderma extract, appropriate amount of sodium carboxymethyl starch, dextrin, and purified water, granulating, drying, grading, mixing, sealing and packaging with granule packaging machine, and making into granule.

Example 4 preparation of granule 2

1.1 formulation

600 parts of rhizoma polygonati, 300 parts of purslane, 200 parts of lucid ganoderma fruit bodies and 20 parts of ginseng total saponins;

wherein, the ginseng total saponin is purchased from the market (the content of the ginseng total saponin is more than or equal to 90 percent), and 20 weight parts of the ginseng total saponin is equivalent to 167 weight parts of ginseng medicinal materials.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

(b) Preparation of the extract

Decocting 600 weight parts of rhizoma Polygonati in water for 3 times, each time for 1.5 hours, filtering the water extract, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, fine extracting, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C).

300 parts by weight of purslane is extracted by 70 percent ethanol under reflux for 2 times, each time lasts for 3 hours, and the ethanol extract is decompressed and concentrated into purslane extract with the relative density of 1.30(60 ℃), thus obtaining the purslane extract.

Decocting 200 parts by weight of ganoderma lucidum fruiting body with water for 2 times, each time for 3 hours, filtering the water extract, concentrating the filtrate under reduced pressure to a concentrated solution with the relative density of 1.10(60 ℃), adding 3 times of ethanol for alcohol precipitation and standing for 24 hours, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the water solution with ultrafiltration membranes with the molecular weight grades of 500KDa and 5KDa in sequence, and concentrating the middle parts of 5KDa and 500KDa under reduced pressure to purslane extract with the relative density of 1.30(60 ℃), thus obtaining the purslane extract.

1.3 preparation of granule 2

Mixing Ginseng radix total saponin, rhizoma Polygonati extract, herba Portulacae extract and Ganoderma extract with appropriate amount of sodium carboxymethyl starch, dextrin and purified water, granulating, drying, grading, mixing, sealing and packaging with granule packaging machine, and making into granule.

EXAMPLE 5 preparation of tablet 1

1.1 formulation

850 parts of rhizoma polygonati, 540 parts of purslane, 220 parts of lucid ganoderma fruit bodies and 40 parts of ginseng stem and leaf total saponins;

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

850 parts of rhizoma polygonati, 540 parts of purslane and 220 parts of lucid ganoderma sporocarp are cleaned, washed, sterilized and dried, and then crushed by a crusher.

(b) Preparation of the extract

Decocting 850 weight parts of rhizoma Polygonati in water for 2 times, each time for 2 hours, filtering the water extract, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, fine extracting, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C).

Extracting herba Portulacae 540 weight parts with 50% ethanol under reflux for 2 times, each time for 2 hr, and concentrating the ethanol extractive solution under reduced pressure to obtain herba Portulacae extract with relative density of 1.30(60 deg.C).

Decocting Ganoderma encarpium 220 weight parts in water for 2 times, each time for 2 hr, filtering the water extract, concentrating the filtrate under reduced pressure to obtain concentrated solution with relative density of 1.10(60 deg.C), adding 3 times of ethanol, precipitating with ethanol, standing for 12 hr, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the water solution with ultrafiltration membranes of 500KDa and 5KDa molecular weight grades, and concentrating the middle parts of 5KDa and 500KDa under reduced pressure to obtain Ganoderma extract with relative density of 1.30(60 deg.C) to obtain Ganoderma extract.

1.3 preparation of tablet 1

Mixing caulis Et folium Ginseng total saponin, rhizoma Polygonati extract, herba Portulacae extract, Ganoderma extract, appropriate amount of sodium carboxymethyl starch and purified water, granulating, drying, adding magnesium stearate, mixing, and tabletting to obtain tablet.

EXAMPLE 6 preparation of tablet 2

1.1 formulation

850 parts of rhizoma polygonati, 540 parts of purslane, 220 parts of lucid ganoderma fruit bodies and 40 parts of ginseng total saponins;

wherein, the ginseng total saponin is purchased from the market (the content of the ginseng total saponin is more than or equal to 90 percent), 40 weight parts of the ginseng total saponin is equivalent to 330 weight parts of ginseng medicinal materials.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

(b) Preparation of the extract

Decocting 850 weight parts of rhizoma Polygonati in water for 3 times, each time for 2 hours, filtering the water extract, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, fine extracting, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C) to obtain rhizoma Polygonati extract.

Extracting herba Portulacae 540 weight parts with 80% ethanol under reflux for 2 times, each time for 2 hr, and concentrating the ethanol extractive solution under reduced pressure to obtain herba Portulacae extract with relative density of 1.30(60 deg.C). .

Decocting Ganoderma encarpium 220 weight parts in water for 2 times, each for 3 hr, filtering the water extract, concentrating the filtrate under reduced pressure to obtain concentrated solution with relative density of 1.10(60 deg.C), adding 3 times of ethanol, precipitating with ethanol, standing for 24 hr, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the water solution with ultrafiltration membranes of 500KDa and 5KDa molecular weight grades, and concentrating the middle parts of 5KDa and 500KDa under reduced pressure to obtain Ganoderma extract with relative density of 1.30(60 deg.C) to obtain Ganoderma extract.

1.3 preparation of tablet 2

Mixing Ginseng radix total saponin, rhizoma Polygonati extract, herba Portulacae extract and Ganoderma extract with appropriate amount of sodium carboxymethyl starch, dextrin and purified water, granulating, drying, adding magnesium stearate, mixing, and tabletting to obtain tablet.

EXAMPLE 7 preparation of Capsule 1

1.1 formulation

800 parts of rhizoma polygonati, 350 parts of purslane, 300 parts of lucid ganoderma fruit body and 25 parts of ginseng stem leaf total saponin;

wherein, the total saponins of ginseng stem and leaf are purchased from the market (the content of the total saponins of ginseng stem and leaf is more than or equal to 90 percent), and 25 weight parts of the total saponins of ginseng stem and leaf are equivalent to 250 weight parts of ginseng medicinal material.

1.3 preparation of extract of crude drug

(a) Medicinal material crushing process

800 parts of rhizoma polygonati, 350 parts of purslane and 300 parts of lucid ganoderma sporocarp by weight are cleaned, washed, sterilized, dried and crushed by a crusher.

(b) Preparation of the extract

Decocting 850 weight parts of rhizoma Polygonati in water for 2 times, each time for 2 hours, filtering the water extract, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C) to obtain rhizoma Polygonati extract.

1.3 preparation of Capsule 1

Mixing caulis Et folium Ginseng total saponin, rhizoma Polygonati extract, herba Portulacae extract, Ganoderma extract, appropriate amount of sodium carboxymethyl starch, dextrin, and purified water, granulating, drying, and making into capsule.

EXAMPLE 8 preparation of Capsule 2

1.1 formulation

800 parts of rhizoma polygonati, 350 parts of purslane, 300 parts of lucid ganoderma fruit body and 25 parts of ginseng total saponin;

wherein, the ginseng total saponin is purchased from the market (the content of the ginseng total saponin is more than or equal to 90 percent), and 25 weight parts of the ginseng total saponin is equivalent to 208 weight parts of ginseng medicinal materials.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

(b) Preparation of the extract

Decocting 850 weight parts of rhizoma Polygonati in water for 3 times, each time for 2 hr, filtering the water extractive solution, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C) to obtain rhizoma Polygonati extract.

Extracting herba Portulacae 540 weight parts with 80% ethanol under reflux for 2 times, each time for 2 hr, and concentrating the ethanol extractive solution under reduced pressure to obtain herba Portulacae extract with relative density of 1.30(60 deg.C).

Decocting Ganoderma encarpium 220 weight parts in water for 2 times, each for 3 hr, filtering the water extract, concentrating the filtrate under reduced pressure to obtain concentrated solution with relative density of 1.10(60 deg.C), adding 3 times of ethanol, precipitating with ethanol, standing for 24 hr, filtering or centrifuging to obtain precipitate, dissolving with water, ultrafiltering the water solution with ultrafiltration membranes of 500KDa and 5KDa molecular weight grades, concentrating the middle part of 5KDa and 500KDa under reduced pressure to obtain Ganoderma extract with relative density of 1.30(60 deg.C), and obtaining Ganoderma extract.

1.3 preparation of Capsule 2

Mixing Ginseng radix total saponin, rhizoma Polygonati extract, herba Portulacae extract and Ganoderma extract with appropriate amount of sodium carboxymethyl starch, dextrin and purified water, granulating, drying, and making into capsule.

EXAMPLE 9 preparation of pellet 1

1.1 formulation

840 parts of rhizoma polygonati, 630 parts of purslane, 250 parts of lucid ganoderma fruit body and 30 parts of ginseng stem leaf total saponin;

wherein, the ginseng stem and leaf total saponins are purchased from the market (the content of the ginseng stem and leaf total saponins is more than or equal to 90 percent), and 30 weight parts of the ginseng stem and leaf total saponins are equivalent to 300 weight parts of ginseng medicinal materials.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

840 parts of rhizoma polygonati, 630 parts of purslane and 250 parts of lucid ganoderma sporocarp are cleaned, washed, sterilized and dried, and then crushed by a crusher.

(b) Preparation of the extract

Decocting rhizoma Polygonati 840 parts by weight in water for 2 times, each for 2 hours, filtering the water extract, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C).

630 parts by weight of purslane is extracted by 50 percent ethanol under reflux for 2 times, each time lasts for 2 hours, and the ethanol extract is decompressed and concentrated into purslane extract with the relative density of 1.30(60 ℃), thus obtaining the purslane extract.

Decocting 250 parts by weight of ganoderma lucidum sporocarp with water for 2 times, each time for 2 hours, filtering the water extract, concentrating the filtrate under reduced pressure to obtain a concentrated solution with the relative density of 1.10(60 ℃), adding 3 times of ethanol for alcohol precipitation and standing for 12 hours, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the water solution by ultrafiltration membranes with the molecular weight grades of 500KDa and 5KDa in sequence, and concentrating the middle parts of 5KDa and 500KDa under reduced pressure to obtain a water extract with the relative density of 1.30(60 ℃).

1.3 pill 1 preparation

Making into pill with total saponins of caulis Et folium Ginseng, rhizoma Polygonati extract, herba Portulacae extract, Ganoderma extract and dextrin.

EXAMPLE 10 preparation of pill 2

1.1 formulation

840 parts of rhizoma polygonati, 630 parts of purslane, 250 parts of lucid ganoderma fruit body and 30 parts of ginseng total saponin;

wherein, the ginseng total saponin is purchased from the market (the content of the ginseng total saponin is more than or equal to 90 percent), and 30 weight parts of the ginseng total saponin is equivalent to 250 weight parts of ginseng medicinal materials.

1.2 preparation of extracts of crude drugs

(a) Medicinal material crushing process

(b) Preparation of the extract

Decocting rhizoma Polygonati 840 parts by weight in water for 3 times, each for 3 hours, filtering the water extract, concentrating under reduced pressure to obtain extract with relative density of 1.20(60 deg.C), adding ethanol until the ethanol content reaches 65 wt%, and concentrating under reduced pressure to obtain rhizoma Polygonati extract with relative density of 1.30(60 deg.C).

630 parts by weight of purslane are extracted by 60 percent ethanol under reflux for 3 times, each time lasts for 1.5 hours, and the ethanol extract is decompressed and concentrated into purslane extract with the relative density of 1.30(60 ℃), thus obtaining the purslane extract.

Decocting Ganoderma encarpium 250 weight parts in water for 2 times, each for 3 hr, filtering the water extract, concentrating the filtrate under reduced pressure to obtain concentrated solution with relative density of 1.10(60 deg.C), adding 3 times of ethanol, precipitating with ethanol, standing for 24 hr, filtering or centrifuging, re-dissolving the precipitate with water, ultrafiltering the water solution with ultrafiltration membranes of 500KDa and 5KDa molecular weight grades, and concentrating the middle parts of 5KDa and 500KDa under reduced pressure to obtain Ganoderma extract with relative density of 1.30(60 deg.C) to obtain Ganoderma extract.

1.3 pill 2 preparation

Preparing the total ginsenoside, the water extract of rhizoma polygonati, the alcohol extract of purslane, the water extract of ganoderma lucidum and ethanol precipitation of 5 KDa-500 KDa and a proper amount of dextrin into pills, namely obtaining the pills.

In examples 1-10, the Ganoderma lucidum fruiting body extract contains 5% -10% of polysaccharide and 25% -35% of protein.

EXAMPLE 11 pharmacological Experimental study

1. Main agent and medicine

Metformin (glauco, shanghai schlubo pharmaceutical limited, 0.85 g/tablet, lot No. 1609076), rosiglitazone (glatiramer limited, 4 mg/tablet, lot No. 1608051), Streptozotocin (STZ): sigma, USA (s-0130) from Shanghai Meiji Biotechnology, Inc. Citric acid, urethane, and the like.

2. Test animal

1) Sprague-Dawley (SD) rats, clean grade, male, body weight 200-250 g, 70, provided by the animal testing center of university of medicine in Shanghai.

2) db/db diabetic mice, clean grade, half male and female, weight 20-25 g, 5-8 weeks old, 28, provided by Shanghai pharmaceutical institute experimental center of Chinese academy of sciences.

3) C57BL/6J genetically engineered mouse, clean grade, male, 20-25 g weight, 5-8 weeks old, 10, provided by Shanghai pharmaceutical institute of Chinese academy of sciences experimental center.

3. Construction of animal models

1) Rats with type 2 diabetes induced by Streptozotocin (STZ)

A control group is 10 normal SD rats on normal diet, 60 (mice die during administration) rats take high-fat and high-energy diet, animals are positioned in an environment with the temperature of 22-25 ℃, and the animals are molded by intraperitoneal injection of STZ (STZ is dissolved in 0.1M citric acid/sodium citrate buffer solution with pH of 4.5) at the temperature of 40mg/kg, and FBG (fiber Bragg Grating) of the STZ-injected rats is determined as type 2 diabetes model rats. The molded rats were randomly divided into a model group (without any drug), a hypoglycemic agent low dose group (150mg/kg) prepared in example 4, a hypoglycemic agent high dose group (450mg/kg) prepared in example 4, a metformin group (250mg/kg), and a rosiglitazone group (3 mg/kg). Each group of rats had free access to water and normal food daily, and were administered once a day by gavage for 30 days, and blood was taken from the tail vein every 10 days to measure blood glucose and body weight at the same time. Before the experiment, 10U/kg of insulin is injected into half of abdominal cavity of each group, the same amount of normal saline is injected into half of abdominal cavity, the uratan with the volume of 5mL/kg is used for anesthesia after 10min, blood is taken from abdominal cavity, serum is taken by centrifugation, the concentration of serum insulin is measured by a radioimmunoassay, and the concentration of blood glucose is measured by a glucose oxidase method.

2) db/db genotype type 2 diabetic mice

db/db type 2 diabetic mice were randomly divided into 5 groups according to fasting blood glucose, the mean difference of fasting blood glucose after grouping was not more than 2mmol/L, 10 normal C57BL/6J mice were used as a control group, 28 (mice died during administration) db/db2 diabetic mice were averagely divided into 4 groups, a model group (without any drug), a low-dose group (300mg/kg) of hypoglycemic granules prepared in example 4, a high-dose group (900mg/kg) of hypoglycemic granules prepared in example 4, and a metformin group (250 mg/kg). The administration is 1 time per day for 4 weeks. Body weight was measured weekly, and fasting blood glucose was measured weekly by tail snip. Before the experiment, 13U/kg of insulin is injected into half of abdominal cavity of each group, equal amount of normal saline is injected into half of abdominal cavity, cervical vertebra is cut off after 10min for killing, eyeballs are picked for taking blood, serum is centrifugally taken, serum insulin concentration is measured by a radioimmunoassay, and blood glucose concentration is measured by a glucose oxidase method.

3) Influence on serum insulin concentration, resistance index and secretion index

The detection principle is as follows: by using the liquid phase competitive inhibition principle, a sample to be detected or a standard substance reacts with limited antiserum, after a period of time, labeled antigen is added for competitive binding reaction, after the reaction is completed, an immune separating agent is added, an antigen-antibody compound is separated, the radioactivity of the compound is measured, the binding rate of each standard tube is calculated, a standard curve is drawn, and the concentration of the sample is checked.

4. Results of the experiment

1) Blood glucose Effect of STZ-induced type 2 diabetic rats

Blood glucose levels in STZ-induced type 2 diabetic rats are shown in table 6.

TABLE 6 STZ-induced type 2 diabetes mellitus rats blood glucose for 30 days

Results are expressed as mean ± SD, control group n-10, hypoglycemic particles group n-8, metformin group n-8, rosiglitazone group n-7, p <0.05vs. model group, p <0.01vs. model group.

Before administration, the blood sugar of rats in the model group is obviously increased (p is less than 0.01) compared with that in the normal group, and as can be seen from table 6, after 30 days of gastric lavage, the blood sugar of the group treated by 450mg/kg of the hypoglycemic particles prepared in example 4 is obviously reduced (p is less than 0.01) compared with that of rats in the model group, and the blood sugar reducing effect is equivalent to that of 250mg/kg of metformin and 3mg/kg of rosiglitazone. In addition, the blood sugar reducing effect of the blood sugar reducing particle treatment group of 450mg/kg prepared in the embodiment 4 is better than that of the blood sugar reducing particle treatment group of 150mg/kg, the dosage dependence relationship is presented, and the blood sugar of rats in the blood sugar reducing particle treatment group of 450mg/kg is reduced along with the time and is in the time dependence relationship.

2) Blood glucose impact in db/db genotype type 2 diabetic mice

db/db since it is a spontaneous type 2 diabetic mouse, blood glucose will reach diabetic levels (11.1mmol/L) at 5 weeks of age, then gradually rise to about 25mmol/L at 12 weeks of age and 33mmol/L at 16 weeks of age. The change in blood glucose after 4 weeks of administration in db/db mice is shown in Table 7.

TABLE 7 db/db type 2 diabetic mice 4 weeks blood glucose

Results are expressed as mean ± SD, control n ═ 10, model n ═ 7, 300mg/kg hypoglycemic particles n ═ 7, 900mg/kg hypoglycemic particles n ═ 6, metformin n ═ 6, p <0.01vs. control, p <0.05vs. model, p <0.01vs. model.

As can be seen from Table 7, the 900mg/kg treatment group of hypoglycemic particles prepared in example 4 showed a significant decrease in blood glucose (p <0.01) compared to the model group, and the hypoglycemic effect was comparable to that of 250mg/kg metformin. And the blood sugar reducing effect of the 900mg/kg blood sugar reducing particle treatment group is better than that of the 300mg/kg blood sugar reducing particle treatment group, and the dose dependence relationship is presented, and different from the STZ-induced type 2 diabetes rat model, because the self characteristic of the db/db mouse is that the blood sugar is increased along with the increase of time, the blood sugar of the mice of each group is increased along with the extension of the test time in the test, but the difference between the groups still exists.

3) Influence of serum insulin concentration, resistance index and secretion index of STZ-induced type 2 diabetic rat

30 days after administration, the serum insulin concentration, insulin resistance index and insulin secretion index of rats are shown in Table 8.

TABLE 8 serum insulin concentration, resistance index and secretion index of STZ-induced type 2 diabetic rats in each group

The results are expressed as mean ± SD, control group n-10, hypoglycemic particles group n-8, metformin group n-8, rosiglitazone group n-7, p<0.01vs. control group,. p<0.01vs. the model set,^#p<0.05vs. model set.

As can be seen from Table 8, the insulin concentration and insulin secretion index of the type 2 diabetic rat are significantly decreased compared to the normal control group, indicating that the molding was successful. Compared with a model group, the concentration of insulin and the insulin secretion index are obviously increased after the treatment of the blood sugar reducing particles, and the blood sugar reducing particles are in a dose dependent relationship, and the increasing effect is equivalent to that of metformin and rosiglitazone. Clinical application proves that both metformin and rosiglitazone have good effect of improving insulin resistance, compared with a normal control group, the insulin resistance index of a rat with type 2 diabetes is obviously increased, and the insulin resistance index is obviously reduced after treatment by the blood sugar reducing granules, and has the effect equivalent to the effect of reducing the insulin resistance index of metformin and rosiglitazone.

4) Influence of serum insulin concentration, resistance index and secretion index of db/db genotype type 2 diabetic mice

4 weeks after administration, serum insulin concentration, insulin resistance index, and insulin secretion index of db/db type 2 diabetic mice are shown in Table 4.

TABLE 9 serum insulin concentration, resistance index and secretion index for each group of db/db type 2 diabetic mice

Results are expressed as mean ± SD, control group n ═ 10, model group n ═ 7, 300mg/kg hypoglycemic particles group n ═ 7, 900mg/kg hypoglycemic particles group n ═ 6, metformin group n ═ 6, × <0.05vs. model group, × <0.01vs. model group.

As can be seen from Table 9, the insulin concentration in the db/db mouse model group was slightly increased compared to the normal control group, but there was no significant difference, but the secretion index was significantly decreased compared to the control group. Compared with the model group, the blood sugar reducing particle group can obviously reduce the insulin resistance index, namely the blood sugar reducing particles obviously improve the sensitivity of a db/db type 2 diabetes mouse receptor to insulin, thereby reducing the concentration content of the insulin in blood. The insulin resistance index and the insulin concentration present a dose-dependent relationship, the higher the dosage of the hypoglycemic particles, the lower the insulin resistance index, the lower the insulin concentration, the lower the dosage, the higher the insulin resistance index and the higher the insulin concentration. The insulin secretion index is not different from that of the model group, and compared with that of the model group, the insulin concentration and the insulin secretion index of the metformin group are obviously improved. Compared with a control group, the insulin resistance index of the model group is obviously increased, and the insulin resistance index is obviously reduced after the treatment of the blood sugar reducing particles, has obvious difference and is in a dose dependent relation, and has the same effect as the reduction effect of the insulin resistance index of the metformin group.

The above experimental results show that the composition (especially the pharmaceutical composition) of the present invention can be effectively used for preventing, treating and/or improving diabetes and/or diabetic complications.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims

1. A composition comprising a crude drug or an extract thereof, wherein the crude drug comprises:

2. The composition of claim 1, wherein the raw herbs comprise:

3. the composition of claim 1, wherein the raw herbs comprise:

4. the composition of claim 1, wherein the crude drug or extract thereof comprises:

5. The composition of claim 1, wherein the crude drug or extract thereof comprises:

one or more middle-jiao and Qi tonifying medicinal materials selected from the following groups:

1500 weight portions of sealwort, astragalus and codonopsis pilosula:

one or more liver-nourishing and spleen-invigorating medicinal materials selected from the following groups:

100 portions of ganoderma lucidum, tuckahoe and yam;

one or more extracts of yin-nourishing and fluid-generating herbs selected from the group consisting of:

10-50 parts by weight of ginseng extract, ophiopogon root extract, rehmannia root extract and pseudo-ginseng extract; and

one or more heat-clearing and detoxifying medicinal materials selected from the following groups:

0-1000 parts of purslane, kudzu root and scutellaria baicalensis.

6. The composition of claim 1, wherein the crude drug or extract thereof comprises:

7. the composition of claim 1, wherein the crude drug or extract thereof comprises: rhizoma Polygonati extract, Ganoderma extract, ginsenoside, and optionally herba Portulacae extract.

8. The composition of claim 1, wherein the composition is in the form of a tablet, capsule, granule, pill, powder, oral liquid, buccal tablet, or aerosol.

9. A method of preparing the composition of claim 1, comprising: mixing the raw materials or extracts thereof and optionally a carrier to form the composition of claim 1.

10. Use of a composition according to claim 1 for the preparation of a medicament for the prevention, treatment and/or amelioration of diabetes and/or diabetic complications.