CN100528191C - Chinese medicine preparation for treating diabetes complication and its preparing method - Google Patents
Chinese medicine preparation for treating diabetes complication and its preparing method Download PDFInfo
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- CN100528191C CN100528191C CNB2004100176734A CN200410017673A CN100528191C CN 100528191 C CN100528191 C CN 100528191C CN B2004100176734 A CNB2004100176734 A CN B2004100176734A CN 200410017673 A CN200410017673 A CN 200410017673A CN 100528191 C CN100528191 C CN 100528191C
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Abstract
The Chinese medicine composition for treating diabetes blood vessel complication contains pharmaceutically acceptable carrier in 1-99.99 wt% and the water extract or water soluble organic solvent extract of medicine material in 0.01-99 wt%. The medicine material includes the first part of Chuanxiong rhizome, leech, astragalus root and/or kudzu vine root with functions of promoting blood circulation to disperse blood clots, nourishing vital energy, cooling and expelling surficial evils; and the second part of cape jasmine, capillary artemisia, Huguenot fern herb and dried orange peel with functions of clearing away heat and toxic material, promoting diuresis and regulating vital energy, with the two parts having the weight ratio of 0.2-5. The present invention also provides the treating method.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation that is used for the treatment of diabetic vascular complications, relate to a kind of Chinese medicine preparation and method for making thereof of treatment diabetic complication of the Chinese medicine medical material that contains activating blood circulation to dissipate blood stasis, heat-clearing and toxic substances removing particularly.
Background technology
Along with progress of human society, living standard constantly improves, and the onset diabetes rate rises year by year, and China's diabetics has surpassed 40,000,000 people at present.The prevalence of diabetics vascular complication is very high, diabetic duration greater than the patient in 10 years in, almost vascular complication in various degree all appears in 100% patient.Vascular complication is the important deadly reason that disables of diabetics.
Think that at present the vascular endothelial function disorder is common pathologic basis (DeMeyer GR et al, the Vascular endothelial dysfunction.Prog.Cardiovasc.Dis of trunk and microangiopathies; 1997 (39): 325-342).Under the endothelial function disturbance state, trunk usually shows as the vasodilation function reduction, the blood coagulation-fibrinolytic mechanism that depend on endothelium and causes the formation of hypercoagulability, local atheromatous plaque and thrombosis unusually; And microangiopathies shows as that the glomerular filtration barrier is impaired, permeability increases, albumen spills, until be developed to glomerular sclerosis and retinal microvascular ooze out, hemorrhage and blind etc.
Recently think that diabetes are not only metabolic disease, still a kind of chronic inflammation disease.The inflammatory mediator level is apparently higher than 2 crowds of (Duncan BB of common people in the diabetics body, Schmidt MI, et al:Low-grade systemic inflammation and the development of type 2 diabetes:theAtherosclerosis Risk in Communities Study.Diabetes 52:1799-1805,2003), diabetics whole body systematicness chronic inflammatory reaction may be one of reason of endothelial function disorder, and directly cause generation and development (Huerta MG, the Nadler JL.et al:Role of inflammatorypathways in the development and cardiovascular complications of type 2diabetes.Curr Diab Rep.2002Oct of vascular complication; 2 (5): 396-402.Review.Biondi-Zoccai GG, AbbateA, et al:Atherothrombosis, inflammation, and diabetes.J Am Coll Cardiol.2003 Apr2; 41 (7): 1071-7.Review.Saraheimo M, Teppo AM et al:Diabetic nephropathy isassociated with low-grade inflammation in Type 1 diabetic patients.Diabetologia.2003 Oct; 46 (10): 1402-7.).
Except positive blood sugar control, blood pressure, the multiple factor of blood fat, the medicine that is used for the treatment of diabetic complication specifically is still rare at present.The tradition traditional Chinese medical science has the experience prescription of a lot of treatment diabetic complications, but rare usefulness follows and levy medical science and estimated, and the mechanism of action of Chinese medicine is known little about it.
In sum, owing to also do not have effectively to treat at present the medicine of diabetic complication, so this area presses for the preparation that exploitation can be treated diabetic complication effectively.
Summary of the invention
Purpose of the present invention just provides a kind of preparation and method for making and the purposes that can effectively treat diabetic complication.
In a first aspect of the present invention, a kind of Chinese medicine composition is provided, it contains
(a) the pharmaceutically acceptable carrier of 1-99.99wt% and
(b) extract of the water extract of the raw medicinal material of 0.01-99wt% or aqueous organic solvent,
Wherein, described raw medicinal material comprises: one or more activating blood circulation to dissipate blood stasis classes, Qi-tonifying drug class, the relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material that (i) are selected from down group: Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae; (ii) be selected from down one or more antipyretic and antidotal types, promoting diuresis to eliminate damp pathogen class, the class of the regulating the flow of vital energy medical material of group: Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, Pericarpium Citri Reticulatae, wherein (i) activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material are 5: 1～1: 5 with the (ii) weight ratio of antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material.
In another preference, described raw medicinal material also comprises at least a auxiliary medical material that is selected from down group:
(iii) one or more auxiliary activating blood circulation to dissipate blood stasis class medical materials: Semen Persicae, Flos Carthami, Olibanum, Myrrha, Caulis Spatholobi, Radix Salviae Miltiorrhizae;
(iv) one or more auxiliary antipyretic and antidotal type medical materials: Rhizoma Phragmitis, Herba Lophatheri, Flos Lonicerae, Herba Violae, Herba Lobeliae Chinensis, Herba Scutellariae Barbatae.
In another preference, when containing described raw medicinal material, its quantity is as follows:
(i) activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material
The Radix Astragali 5～20 parts by weight;
(ii) antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material
Gardenia 5～10 parts by weight;
(iii) auxiliary activating blood circulation to dissipate blood stasis class medical material
Semen Persicae 5～10 parts by weight;
Caulis Spatholobi 5～20 parts by weight;
Radix Salviae Miltiorrhizae 5～20 parts by weight;
(iv) auxiliary antipyretic and antidotal type medical material
Rhizoma Phragmitis 5～20 parts by weight;
Flos Lonicerae 5～20 parts by weight;
More preferably, when containing described raw medicinal material, its quantity is as follows:
(i) activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material
Rhizoma Chuanxiong 5～9 parts by weight;
The Radix Astragali 10～15 parts by weight;
(ii) antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material
Gardenia 5～9 parts by weight;
Herba Artemisiae Scopariae 5～15 parts by weight;
Herba Pteridis Multifidae 5～30 parts by weight;
(iii) auxiliary activating blood circulation to dissipate blood stasis class medical material
Caulis Spatholobi 9～15 parts by weight;
Radix Salviae Miltiorrhizae 9～15 parts by weight;
(iv) auxiliary antipyretic and antidotal type medical material
Rhizoma Phragmitis 9～15 parts by weight;
Herba Lophatheri 15～30 parts by weight;
Flos Lonicerae 9～15 parts by weight;
Herba Violae 15～30 parts by weight;
Herba Lobeliae Chinensis 15～30 parts by weight;
Herba Scutellariae Barbatae 15～30 parts by weight.
In another preference, described raw medicinal material contains: the 3-4 kind that (i) is selected from down group is selected from down one or more activating blood circulation to dissipate blood stasis classes, Qi-tonifying drug class, the relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material of group: Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae; (ii) be selected from down one or more antipyretic and antidotal types, promoting diuresis to eliminate damp pathogen class, the class of the regulating the flow of vital energy medical material of group: Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, Pericarpium Citri Reticulatae.
In a second aspect of the present invention, a kind of preparation method for compositions is provided, described compositions contains (a) pharmaceutically acceptable carrier and (b) water extract of the raw medicinal material of effective dose or the extract of aqueous organic solvent, and described raw medicinal material comprises and is selected from down one or more activating blood circulation to dissipate blood stasis classes, Qi-tonifying drug class, the relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material of organizing: Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae; Be selected from down the group one or more antipyretic and antidotal types, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material: Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, Pericarpium Citri Reticulatae, wherein (i) activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material are 5: 1～1: 5 with the (ii) weight ratio of antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material, and the method comprising the steps of:
(a) with the water of described medical material and 1-20 times of weight or the mixture of aqueous solvent, decocted 1-6 hour to the boiling condition at 80 ℃, obtain mixed liquor;
(b) filter mixed liquor, obtain filtrate,
(c) the filtrate volume is concentrated 5-50 doubly, obtain concentrated solution, i.e. extract;
(d) extract is mixed with pharmaceutically acceptable carrier, form compositions.
In another preference, also comprise step in step (c) with (d): the concentrated solution that obtains is carried out drying, thereby obtain the solids extraction thing; Perhaps
Also comprise step in step (c) with (d): the concentrated solution that obtains is mixed with the 70-99% ethanol of 1-10 times of volume, place after 12-72 hour, reclaim the supernatant that contains alcohol, filter and obtain filtrate.
In another preference, described raw medicinal material also comprises the auxiliary medical material that is selected from down group:
(iii) one or more auxiliary activating blood circulation to dissipate blood stasis class medical materials: Semen Persicae, Flos Carthami, Olibanum, Myrrha, Caulis Spatholobi, Radix Salviae Miltiorrhizae;
(iv) one or more auxiliary antipyretic and antidotal type medical materials: Rhizoma Phragmitis, Herba Lophatheri, Flos Lonicerae, Herba Violae, Herba Lobeliae Chinensis, Herba Scutellariae Barbatae.
In a second aspect of the present invention, the purposes of compositions of the present invention is provided, it is used to prepare the medicine for the treatment of diabetic vascular complications.
In another preference, described medicine is by 1-3 agent for each person every day, and the application dosage of every day is equivalent to 5-500 gram (preferably 20-300 gram, more preferably 50-200 gram) and does total medical material.
Description of drawings
2 groups of patient UAER changed (Md) before and after Fig. 1 had shown treatment.
UAER changed (Md) before and after Fig. 2 had shown the unusual patient treatment of UAER.
Fig. 3 has shown that primary cultured cell (amplification 80) is the paving stone sample and arranges.
Fig. 4 has shown back (second filial generation) cell (amplification 200) that goes down to posterity, visible tube chamber sample growth (arrow place).
Fig. 5 has shown cellular immunization zymetology dyeing CD31 (+) result.
Fig. 6 has shown second filial generation PMEC (Pulmonary Microvascular Endothelial Cells) growth curve.
Fig. 7 has shown the cell counting result of different disposal cultivation after 24 hours.
Fig. 8 has shown the cell growing state (amplification 200 does not add green filter lens) of 5mmol//L glucose initial incubation.
Fig. 9 has shown the cell growing state (amplification 200) when the 5mmol//L glucose was cultivated in 24 hours.
Figure 10 has shown the cell growing state (amplification 200 does not add green filter lens) of 20mmol//L glucose initial incubation.
Figure 11 has shown the cell growing state (amplification 200) when the 20mmol//L glucose was cultivated in 24 hours.
Figure 12 has shown the cell growing state (amplification 200) of 20mmol//L glucose+Chinese medicine initial incubation.
Figure 13 has shown the cell growing state (amplification 200) when 20mmol//L glucose+Chinese medicine was cultivated in 24 hours.
Figure 14 has shown the cell growing state (amplification 200) of 20mmol//L glucose+NAC initial incubation.
Figure 15 has shown the cell growing state (amplification 200) when 20mmol//L glucose+NAC cultivated in 24 hours.
The specific embodiment
The inventor has carried out going deep into extensive studies to the mechanism of diabetic complication and the mechanism of action of the traditional Chinese medical science, has designed the new Chinese medicine heat clearing away side's (Chinese medicine preparation) that invigorates blood circulation.This prescription combines blood circulation promoting and blood stasis dispelling, the heat-clearing and toxic substances removing two big rule of treatment.The Chinese medicine blood circulation promoting and blood stasis dispelling rule of treatment has comprised the effect of anti-endothelial injury, anti-high blood coagulation at diabetic complication, and the heat-clearing and toxic substances removing rule of treatment is at having antiinflammatory action.Exist in type 2 diabetes mellitus, the metabolic syndrome cause of disease and the pathogenesis endothelial injury, hypercoagulability, inflammatory factor to participate in based on thinking at present, in conjunction with traditional medicine, the inventor finds, activating blood circulation to dissipate blood stasis class medical material (as Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae etc.) and antipyretic and antidotal type medical material (as Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, Pericarpium Citri Reticulatae etc.) are combined formed Chinese medicine preparation (the especially extract of water extract or aqueous organic solvent), have the effect of very excellent treatment diabetic complication, finished the present invention on this basis.
It is the important symbol of diabetic nephropathy that the urinary albumin excretion rate increases, reflect the microangiopathies order of severity to a certain extent, and reflect endothelial injury (Esposito K et al widely, Inflammatory cytokineconcentrations are acutely increased by hyperglycemia in humans role of oxidativestress, Circulation 2002; 15:2067-72).First folds in a garment blood capillary form and hemorheologic parameters can reflect finger tip microcirculation situation, be that noinvasive is observed microcirculatory optimal site, also reflect endothelial injury degree (Lin Hua to a certain extent, Chi Jiamin, Li Ming, Deng the relation of .2 type diabetic skin microcirculation change with its microvascular complication. Chinese diabetes magazine .1999,7 (3): 141-143).With urinary albumin excretion rate and nail fold microcirculation comprehensive and quantitative as the diabetic angiopathy observation index, the present invention adopts at random, list is blind, placebo parallel control clinical research methods treated for 24 weeks, confirmed the intervention effect of Chinese medicine preparation of the present invention, and had good safety the type 2 diabetes mellitus vascular lesion.
Blood capillary distributes very extensive, is the significant points that hyperglycemia causes damaging action, and diabetic microvascular complication is the specific lesions that long-term hyperglycemia causes.In order to confirm further Chinese medicine preparation of the present invention knows whether have the protection of ecs effect, and the inventor inquires into its mechanism of action at cellular level.The lung tissue blood capillary is abundant, carry out in vitro study in order to obtain enough capillary endothelium, successful separation and Culture SD induced lung capillary endothelium under different concentration of glucose are cultivated, is inquired into the influence of Chinese medicine preparation cell growth propagation situation of the present invention earlier.Direct help will be provided the mechanism of action of illustrating Chinese medicine preparation of the present invention.
Usually, Chinese medicine preparation of the present invention is a kind of compositions, it contains the pharmaceutically acceptable carrier of (a) 1-99.99wt% and (b) water extract of the raw medicinal material of 0.01-99wt% or the extract of aqueous organic solvent, and its described raw medicinal material comprises that (i) is selected from down one or more activating blood circulation to dissipate blood stasis classes, Qi-tonifying drug class, the relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material of organizing (abbreviating " activating blood circulation to dissipate blood stasis class medical material " as): Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae; (ii) be selected from down one or more antipyretic and antidotal types, promoting diuresis to eliminate damp pathogen class, the class of the regulating the flow of vital energy medical material (abbreviating " antipyretic and antidotal type medical material " as) of group: Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, Pericarpium Citri Reticulatae; Wherein the weight ratio of activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material and antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material is 5: 1～1: 5.
Though can further segment two big class medical materials (being activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material and activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material), for example Rhizoma Chuanxiong, Hirudo are activating blood circulation to dissipate blood stasis class medical materials; The Radix Astragali is a Qi-tonifying drug class medical material; Radix Puerariae is a relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material; Fructus Gardeniae, Herba Pteridis Multifidae are heat clearing away class medical materials; Herba Artemisiae Scopariae is a promoting diuresis to eliminate damp pathogen class medical material; Pericarpium Citri Reticulatae is the class medical material of regulating the flow of vital energy, but unnecessary usually, because the effect of the medical material in each big class has similarity.
In another preference, the raw medicinal material that is used to prepare extract contains: 3-4 kind (more preferably 4 kinds) the activating blood circulation to dissipate blood stasis class medical material that (i) is selected from down group: Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae; (ii) be selected from down 3-4 kind (more preferably 4 kinds) the antipyretic and antidotal type medical material of group: Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, Pericarpium Citri Reticulatae.These extracts have more excellent anti-diabetic complication activity.
Usually, when containing described medical material, the parts by weight of each raw medicinal material are as follows in described mixture:
The preferred parts by weight of parts by weight
(i) activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material
The Radix Astragali 5～20 10～15
(ii) antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material
Gardenia 5～10 5～9
In a preference, also can contain the water extract or the aqueous organic solvent extract of extra auxiliary medical material in the compositions of the present invention.Suitable auxiliary medical material comprises (but being not limited to): one or more auxiliary activating blood circulation to dissipate blood stasis class medical materials: Semen Persicae, Flos Carthami, Olibanum, Myrrha, Caulis Spatholobi, Radix Salviae Miltiorrhizae; And/or (iv) one or more activating blood circulation to dissipate blood stasis class medical materials: Rhizoma Phragmitis, Herba Lophatheri, Flos Lonicerae, Herba Violae, Herba Lobeliae Chinensis, Herba Scutellariae Barbatae.
Usually, the consumption of these extra auxiliary medical materials is as follows:
The preferred parts by weight of parts by weight
(iii) auxiliary activating blood circulation to dissipate blood stasis class medical material
Semen Persicae 5～10 6～9
Caulis Spatholobi 5～20 9～15
Radix Salviae Miltiorrhizae 5～20 9～15
(iv) auxiliary antipyretic and antidotal type medical material
Rhizoma Phragmitis 5～20 9～15
Flos Lonicerae 5～20 9～15
A kind of particularly preferred extract of the present invention is in order to medical material mixture preparation down, and this mixture contains:
| Parts by weight | |
| (i) activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material | |
| Rhizoma Chuanxiong | 5 |
| |
2 |
| The |
10 |
| Radix Puerariae | 3.3 |
| (ii) antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material | |
| Gardenia | 5 |
| Herba Artemisiae Scopariae | 5 |
| Herba Pteridis Multifidae | 5 |
| |
2 |
As used in this description and claims, the title and the latin name of " raw medicinal material " of the present invention are as follows:
Rhizoma Chuanxiong Rhizoma Chuanxiong
Hirudo Hirudo
Radix Astragali Radix Astragali
Radix Puerariae Radix puerariae
Gardenia Fructus Gardeniae
Herba Artemisiae Scopariae Herba Artemisiae Scopariae
Herba Pteridis Multifidae Pteris multifida Poir.
Pericarpium Citri Reticulatae Pericarpium citri Reticulatae
Herba Scutellariae Barbatae Herba Scutellariae Barbatae
Rhizoma Phragmitis Aloe
Herba Lophatheri Herba Lophatheri
Flos Lonicerae Flos Lonicerae
Herba Lobeliae Chinensis Herba Lobeliae Chinesis
Herba Violae Herba violae
These medical materials and method for making thereof all are as known in the art, and for example the Radix Astragali (Astragali Radix or Astragalus root) is the root of leguminous plant Radix Astagali (Astragalus membranaceus Bunge) or other mutation (Leguminosae genus).
The available following method preparation of active component of the present invention (being the extract of medical material): with required medical material water or contain the mixable organic solvent of 5-85% (v/v) water as alcohol (preferred alcohol) extracting, filter the extract that obtains so then, can obtain liquid extract.In addition, also can randomly filtrate be carried out drying with conventional method (as spray drying, lyophilizing or concentrate drying).Active component of the present invention can mix the extract of extractive each raw medicinal material respectively and prepare, and also can obtain by the mixture of extracting medical material.
Extracting can be carried out under room temperature or heating condition, but preferably at 50-100 ℃, more preferably carries out under 60-100 ℃.
In addition, but also before the extracting, also medical material can be soaked a period of time (as 0.1-10 hour or more of a specified duration) with water or aqueous organic solvent.
To the extraction of effective ingredient in the medical material, can single, also can be multiple extraction, so that reduce production costs.A kind of preferred extracting scheme is to use twice extractive medicinal liquid mixed, and concentrates then, thereby has obtained extract of the present invention (liquid state).
In another preference, can in the liquid extract that makes, add correctives (as sucrose), antiseptic (as sodium benzoate) and other suitable additives, thereby make the compositions of liquid state of the present invention, as oral liquid etc.
Also liquid extract can be carried out drying with conventional method (as spray drying, lyophilizing or concentrate drying), obtain solid extract.These solid extracts can be mixed together with pharmaceutical field proper supplementary material and excipient, make various dosage forms such as tablet, capsule, granule.
Usually, extract of the present invention is mixed with suitable carriers can obtain compositions of the present invention.The method that can be used for preparing the present composition is not particularly limited, and the various conventional methods of available this area are as mixing method etc.
In preparation of the present invention, the extract that contains the above-mentioned raw materials medical material is as active component and pharmaceutically acceptable carrier or excipient.
As used herein, " the base stock medical material " refers to (i) 1-4 kind (preferably 2-4 kind, more preferably 3-4 kind) activating blood circulation to dissipate blood stasis class, Qi-tonifying drug class, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature class medical material: Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae to term; (ii) 1-4 kind (preferably 2-4 kind, more preferably 3-4 kind) antipyretic and antidotal type, promoting diuresis to eliminate damp pathogen class, the class of regulating the flow of vital energy medical material: the medical material mixture that Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, Pericarpium Citri Reticulatae are formed.
As used herein, term " compositions of the present invention " comprises pharmaceutical composition and dietary supplement, as long as they contain the extract of base stock medical material or are made of the extract of described base stock medical material basically.In compositions, the extract of described base stock of the present invention or described base stock and other medical materials accounts for the 0.1-99% of composition total weight, preferably accounts for 1-90%, accounts for 5-80% best.In addition, press the dry weight of medical material and calculate, every gram solid composite or every milliliter of fluid composition should restrain corresponding to 0.1-10, more preferably restrain total dried medical material corresponding to 0.2-5, restrain total dried medical material corresponding to 0.5-2.5 best.
As used herein, term " pharmaceutically acceptable carrier " refers to be used for the treatment of the carrier of agent administration, comprises various excipient and diluent.This term refers to some medicament carriers like this: they itself are not necessary active component, and do not have undue toxicity after using.Suitable carriers is well known to those of ordinary skill in the art.(Mack Pub.Co. can find discussing fully about pharmaceutically acceptable excipient in N.J.1991) at Remington ' s Pharmaceutical Sciences.Acceptable carrier can contain liquid on combination of Chinese medicine is learned, as water, saline, glycerol and ethanol.In addition, also may there be complementary material in these carriers, as wetting agent or emulsifying agent, pH buffer substance etc.
In addition, preparation of the present invention or compositions also can contain the chemical compound that other are used for the treatment of diabetic vascular complications or adjuvant therapy of diabetes vascular complication, as insulin etc.Preparation of the present invention or compositions also can be used simultaneously with the other treatment means.
Compositions of the present invention also can contain at least a pharmaceutically acceptable additive, for example correctives (as sucrose, fructose etc.), antiseptic (as sodium benzoate etc.) and pigment.These additives all are to know in the pharmaceutical field.
Extract of the present invention or compositions can be used for treating various diabetic complications, especially diabetic vascular complications.Can carry out administration by conventional route, comprising (but being not limited to): oral, intramuscular, intravenous, subcutaneous or topical.The preferred oral administration.
When making pharmaceutical composition, be the mammal that is applied to the water extract of the base stock medical material (or mixture of base stock medical material and other medical materials) of safe and effective amount or aqueous organic solvent.Wherein this safe and effective amount is generally 5-500 gram for each person every day, and preferably 20-300 restrains, and more preferably 50-200 restrains, by all dried medical material amounts.Usually, but administration every day 1-3 time.Certainly, concrete dosage also should be considered factors such as route of administration, patient health situation, and these all are within the skilled practitioners skill.
Major advantage of the present invention is: Chinese medicine preparation of the present invention is with heat-clearing and toxic substances removing, and blood circulation promoting and blood stasis dispelling is the rule of treatment, and respectively at excessive inflammatory response common in the vascular complication, and blood coagulation-fibrinolytic mechanism is intervened unusually.Chinese medicine preparation of the present invention has the type 2 diabetes mellitus of reduction patient UAER level; improve the curative effect of nail fold microcirculation, have sure protective effect clinical practice safety, no obvious toxic-side effects for the type 2 diabetes mellitus vascular lesion; toleration is better, thereby is with a wide range of applications.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to the condition described in the normal condition, or the condition of advising according to manufacturer.
Take by weighing the raw medicinal material of following quantity, prepare mixture with decoction and alcohol sedimentation technique
| Consumption (kilogram) | |
| Rhizoma Chuanxiong | 90 |
| Hirudo | 36 |
| The Radix Astragali | 180 |
| |
60 |
| Gardenia | 90 |
| Herba Artemisiae Scopariae | 90 |
| Herba Pteridis Multifidae | 90 |
| Pericarpium Citri Reticulatae | 36 |
| Amount to | 672 |
1. decoct
A. get 672 kilograms of crude drugs, add 2500 liters in water for the first time, soak after 2 hours, boil under the condition and extracted 2 hours, filter, it is standby to collect 2200 liters of medicinal liquids.
B. for the second time add 2500 liters in water in the medical material after extracting, boil under the condition and extracted 1 hour, filter, it is standby to collect 2300 liters of medicinal liquids.
C. merge, obtain 4500 medicinal liquids.
2. concentrate
With boulton process (being lower than 0.05MPa), medicinal liquid is concentrated into the 420kg medicinal liquid for 4500 liters, standby.
3. alcohol is handled
A: medicinal liquid 420kg, stir and add 90～98% ethanol of 3 times of volumes, sedimentation 48 hours;
B: get and contain pure supernatant, heating is reclaimed and is removed ethanol (recycling and reusing), obtains medicinal liquid 200kg.
4. water treatment
The a:200kg medicinal liquid left standstill 48 hours, filtered and removed solid, got filtrate 130kg (extract).
5. preparation
Add 71.5 liters of pure water to filtrate 130kg (about 116 liters), join 187.5 liters of medicinal liquid full doses, pour in the clean bottle, 750 bottles, every bottle contains 240ml oral liquid a, every milliliter of mixture is equivalent to the total dried medical material of 3.73 grams.
B: in 110 ℃, the container of 0.01MPa, sterilized 45 minutes;
C: lamp inspection, qualified, packing.
In the present embodiment, adopt the prescription identical, with Asia boil extraction method and spray drying method for preparation granule with embodiment 1.Method is as follows:
1. decoct
A: get 672 kilograms of crude drugs, add 2000 liters in water for the first time, soaked 3 hours, 95 degree stir and extracted 2 hours, filter, and collect 1800 liters of medicinal liquids, and are standby.
B: add 1500 liters in water for the second time, 95 degree stir and extracted 1 hour, filter.Collect 1400 liters of medicinal liquids, standby.
C: merge 3200 liters of acquisition medicinal liquids.
2: concentrate
With 3200 liters of medicinal liquids, be concentrated into 300KG medicinal liquid (density is 1.3 grams per milliliters) with the vacuum film method.
3: spray drying
The 300KG medicinal liquid through 220 degree spray dryinges, is got 90 kilograms of drug powders.
4: dry granulation
In 90 kilograms of drug powders, add 90 kilograms of lactose, be pressed into laminarly, make granule.Granule is encapsulated in the aluminium plastic bag 5 gram/bags (every gram granule is equivalent to the total dried medical material of 3.73 grams).
Preparation embodiment 3-7
Repeat to prepare the method for embodiment 1, difference is, uses the raw medicinal material of following quantity, and also respective change of water and consumption of ethanol.
Make oral liquid b (embodiment 3), c (embodiment 4), d (embodiment 5), e (embodiment 6) and f (embodiment 7) respectively, wherein, the concentration of each oral liquid is corresponding to 3 gram total dried medical material/1ml oral liquids.
Preparation embodiment 8
Repeat to prepare the method for embodiment 2, difference is: raw medicinal material is crushed to the powder of mean diameter 700-850 μ m, and solvent is that concentration is 60% (v/v) ethanol water (consumption is 6 times of each medical material gross dry weight).Medical material flooded 20 hours with solvent.Make oral liquid g.
Preparation embodiment 9-12
Repeat to prepare the method for embodiment 3, difference is: the extract that also additionally contains auxiliary medical material in the medical material mixture:
Make oral liquid h (embodiment 9), i (embodiment 10), j (embodiment 11) and k (embodiment 12), wherein, the concentration of each oral liquid is corresponding to 3 gram total dried medical material/1ml oral liquids.
Test implementation example 1
Chinese medicine preparation of the present invention is to the intervention effect of type 2 diabetes mellitus patient microangiopathies
In the present embodiment, the oral liquid for preparing in the test implementation example 1 is to the intervention effect of type 2 diabetes mellitus patient microangiopathies.
(a), object of study and method
Object of study: type 2 diabetes mellitus patient (being year June February to 2002 calendar year 2001) in hospital's department of endocrinology outpatient service of middle mountain and inpatient
One. inclusion criteria
1. age: 40-75 year
2. be diagnosed as type 2 diabetes mellitus, meet the diagnostic criteria of WHO1999 consultation report
3. in diabetic duration＞March, closely February, glycemic control was steady
Two, exclusion standard
1.1 type diabetes or specific type diabetes, or there are diabetes acute complications (ketoacidosis, non-ketosis height oozes stupor, hypoglycemic coma), severe infections (respiratory tract, urinary tract, skin and deep abscess)
2. gestation and women breast-feeding their children
3.ALT＞113u/l (1.5 times of upper limits of normal)
4. creatinine (Cr)＞170umol/l
5. malignant tumor medical history
6. other major diseases can't not followed up a case by regular visits to the person on time
7. add with ACEI or ARB class medicine person in nearly January.
Three, observation index MAIN OUTCOME MEASURES:
1,24h microdose urine protein quantitative (UAER)
2, nail fold microcirculation is observed
Adopt the Microcirculatory Image processing system of the strong letter section in Wuxi instrument company limited to carry out the nail fold microcirculation detection.Choose with fingernail most proximal end blood capillary be point of observation from blood capillary form, blood flow dynamically, blood vessel ambient state three aspects observe 20 indexs.Nail fold microcirculation image processing system software carries out quantitative, the scoring of brain comprehensive to observed index, and the high more explanation microcirculation disturbance of integrated value is serious, otherwise then light.
Table 1 nail fold microcirculation observation index
Less important observation index: vWF, CRP
Testing program
One. EXPERIMENTAL DESIGN: this test at random, single blind, placebo parallel control clinical trial
Two. dosage regimen: the patient who meets selected and exclusion standard through the screening after date (random table is counted odd even method) at random enters experimental group and matched group.Experimental group and matched group give Chinese medicine preparation 3 * 10ml/ every day (from this data computation, dosage is equivalent to 3 * 36 and restrains dried medical material/every day) and the placebo 3 * 10mltid po of embodiment 1 respectively.This test was carried out for 24 weeks altogether, and per 4 weeks follow up a case by regular visits to once.
Three. experiment process
Table 2. experiment process
(b) result
One. follow up a case by regular visits to situation
Totally 71 routine patients enter the present invention through the screening phase, experimental group 37 people wherein, matched group 34 people.The Chinese medicine preparation in 24 weeks treatment (experimental group 32 people) or placebo treatment (matched group 28 people) before and after 60 people finish.Among the unusual patient of totally 30 routine UAER, experimental group 15 examples, matched group 15 examples.26 people finish treatment (experimental group 14 examples, matched group 12 examples).Lose the visit reason and see Table the no significance difference (P＞0.05) that distributes between 3,2 groups.
Finish in January, 2003 from the selected beginning of the first routine patient calendar year 2001 December to last example and to follow up a case by regular visits to, front and back are lasted 14 months altogether.
The research of table 3. Chinese medicine preparation is lost and is visited reason
Two. the object of study baseline clinical characteristics
71 the example those selected age 62 (56-68) year, man/women ratio is 35/36.Be divided into experimental group (37 example) at random, matched group (34 example).Remove baseline vWF between two groups, HDL-C, the Cr difference has outside the statistical significance, age, sex, body fat parameter, blood glucose, blood pressure, blood lipid level, UAER, CRP, nail fold microcirculation feature, hepatic and renal function, the equal no difference of science of statistics of routine blood test baseline case.
Among those selected, have the patient of 27 examples (38.0%) microalbuminuria phase in 71 examples, a large amount of albuminuria patients of 3 examples (4.4%) account for 42.3% altogether in all object of study.Once there were MAU medical history and this to find the unusual patient of UAER totally 32 examples, accounted for 45.1%.Occur microalbuminuria patient distributional difference in 2 groups during baseline and do not had significance.
Three. the Chinese medicine preparation efficacy result
1. MAIN OUTCOME MEASURES-UAER
(1) 2 groups of all patient UAER situations of change analyses in treatment front and back (table 4, Fig. 1)
In all those selected, the decline behind the experimental group UAER horizontal stretcher has statistical significance (P=0.000), and UAER does not have the significance difference before and after the treatment of control group.Proofread and correct two groups of ages, sex, the difference P value that UAER changes before and after experimental group and the treatment of control group after the baseline UAER level is 0.057.
2 groups of patient UAER change before and after table 4. treatment
(2) UAER situation of change before and after the unusual patient treatment of baseline UAER (table 5, Fig. 2)
Finish among the 26 unusual patients of routine baseline UAER of test, the reduction of experimental group UAER has statistical significance (P=0.01), and matched group changes not statistically significant.Proofread and correct two groups of ages, sex, two groups of P values that change differences of baseline UAER level are 0.081.
Change before and after the unusual patient treatment of table 5.UAER
(2) experimental group UAER fall and influence factor's correlation analysis (table 6) thereof
Experiment with computing group UAER treats the difference after preceding and the treatment, i.e. UAER fall.Same body fat parameter, blood glucose, blood pressure and blood fat, FFA, vWF, the index amplitudes of variation such as CRP calculated.Analyze UAER fall and baseline body fat parameter, blood glucose, blood pressure and blood fat, FFA, vWF, indexs such as CRP, and the dependency of these index falls.The Spearman correlation analysis shows UAER fall and UAER, vWF, FBG, 2hBG, each parameter baseline values of HbA1c and LDL-C, and fasting glucose fall, cholesterol fall dependency tool statistical significance (P＜0.05).
Table 6. treatment group UAER changes correlation analysis (Spearman correlation analysis)
2. MAIN OUTCOME MEASURES-nail fold microcirculation changes
Table 7 shows, test group and matched group baseline form integration, fluidised form integration, loop Zhou Jifen, total mark tool comparability.During 24 weeks, test group form integration increases by 0.12 (p=0.31) than baseline, matched group is than baseline decline 0.05 (p=0.60), and test group form integration 0.04 is lower than matched group form integration 0.06, but two groups of form integration comparison difference do not have significance (p=0.31).Two groups of form integration amplitude of variation comparison difference do not have significance (p=0.27).Prompting Chinese medicine does not change nail fold microcirculation form integration.During 24 weeks, test group fluidised form integration fall is big than matched group, significance (p=0.27), and prompting Chinese medicine improves nail fold microcirculation fluidised form integration.During 24 weeks, test group treatment back loop Zhou Jifen descends and has statistical significance (p＜0.01), does not see obvious decline after the treatment of control group, and prompting Chinese medicine has the nail fold microcirculation of improvement loop week integral action.During 24 weeks, the test group total mark is than baseline decline 1.65 (p=0.008), and matched group increases by 0.82 (p=0.13) than baseline, and test group total mark 2.89 is lower than matched group integration 5.4, and there was a significant difference (p=0.000).Test group total mark fall is big than matched group, and there was a significant difference (p=0.37).Prompting Chinese medicine has the effect of the nail fold microcirculation of improvement total mark.
Nail fold microcirculation comprehensive and quantitative index compares (integration, mean value SD) before and after table 7 treatment
3. less important observation index-vWF, CRP
VWF descends after the treatment of control group statistical significance (P=0.01), and experimental group changes no significance.But the difference not statistically significant (P=0.835) that changes between two groups behind the check baseline.Change no significance before and after the CRP treatment, the difference between two groups of variations does not have significance.
4. blood glucose, blood pressure, blood fat, body fat parameter situation of change
Between the experimental and control group, compare after 24 weeks of treatment with before the treatment, above index changes the equal not statistically significant of difference.
5. safety indexes evaluation
Treated for 24 weeks, none routine patient occurs than the unusual or original situation about increasing the weight of unusually of 0 all kainogenesises.In the therapeutic process, the erythrocyte counting, hemoglobin, leukocyte technology and platelet count do not have significance and change.The treatment back liver, renal dysfunction all do not occur for 2 groups.Overall toleration is good.
Conclusion
By a definite date 24 weeks at random, single blind, placebo parallel control clinical trial confirms that Chinese medicine preparation of the present invention can effectively reduce type 2 diabetes mellitus patient UAER;
2. Chinese medicine preparation of the present invention improves the nail fold microcirculation state, confirms that this side has the effect that improves the type 2 diabetes mellitus vascular lesion.
3. the effect that Chinese medicine preparation of the present invention improves the type 2 diabetes mellitus vascular lesion does not rely on blood sugar lowering, blood pressure and improves the effect of plasma lipid profile.
4. Chinese medicine preparation clinical practice safety, no obvious toxic-side effects, toleration is good.
Test implementation example 2
Chinese medicine preparation of the present invention is to the influence of endotheliocyte multiplication capacity
In the present embodiment, test the influence of Chinese medicine preparation of the present invention to the endotheliocyte multiplication capacity.
(a) materials and methods
One, experimental animal
Male Sprague Dawley rat, at 1 monthly age, body weight 80-100g purchases the laboratory animal portion in Medical Center of Fudan University, is the cleaning level; Freely drink water, take food.
Two, cell culture and evaluation
1.SD the induced lung capillary endothelium is former be commissioned to train foster: adopt the growth characteristics selection method, dehematize extracellular when promptly utilizing the lung tissue piece to cultivate 60-72 hour, other cells do not leave piece of tissue as yet and microvascular endothelial is swum out of at first, go piece of tissue this moment, stays to have only hemocyte and microvascular endothelial in the culture bottle.Hemocyte is eliminated because of suspension growth for the back automatically through passing 1-2, and what be left promptly is pure endotheliocyte.
2. cell is identified: utilize PMEC (Pulmonary Microvascular Endothelial Cells) endoglin expression CD31 antigen, endochylema does not contain the W-P corpusculum so endochylema does not contain vWF antigen, and cell is the arrangement of paving stone sample, 4 characteristics of tube chamber sample growth are comprehensively judged the cell source with cellular morphology under ABC immunoenzymatic staining, flow cytometer inspection, the inverted microscope.
Three, cell purity analysis
Utilize the shared percentage ratio of significant antibody (+) cell to represent the principle of cell purity to identify the purity of cultured cell.Get 2 bottles of (25em of second filial generation SD induced lung capillary endothelium of cultivation
2) the row flow cytometry analysis.
Four, cell growth curve is drawn and the cell viability detection
This is tested used cell and must meet and be in exponential phase and cell viability greater than 95% these two requirements, so will determine that earlier cell meets the requirements before the experiment grouping.First generation endotheliocyte is inoculated in 96 orifice plates with 12000 cells/well after with 0.25% trypsinization, takes out 3 holes counting then every day, and carries out platform and expect blue dyeing.Changed liquid once in per 3 days.
Five, Chinese medicine preparation of the present invention is cultivated the influence of endothelial cell proliferation to the 20mmol/L glucose:
Observe of the influence of high sugar to endothelial cell proliferation, and high sugar add Chinese medicine (content be add in 100 milliliters of culture fluid 1 milliliter of oral liquid a), NAC is to the influence of endothelium propagation, inquires into the Chinese medicine effect from the cell proliferation aspect.
(b) result
One, cell is identified
Cultured cells is the paving stone sample arranges, and the growth of tube chamber sample meets endothelial cells exhibit.ABC immunoenzyme method dyeing CD31 (+), and flow cytometer detects CD31 (+) cell and account for 94.04% of total cellular score shows that most cells expresses CD31 (+), meets the PMEC (Pulmonary Microvascular Endothelial Cells) performance.VWF (+) cell accounts for 1.1% of total cellular score, shows that cultured cells do not express vWF substantially, meets the performance of capillary endothelium.We think that cultured cell is the capillary endothelium of lung according to above 4 aspects.
The cellular morphology observed result as shown in Figure 3.Under the inverted microscope, the primary cell of cultivation is the paving stone sample and arranges.Fig. 4 shows the growth of cell tube chamber sample for the back cell that goes down to posterity, arrow place.
ABC immunoenzyme method coloration result as shown in Figure 5, showed cell film CD31 dye (+).
Cells were tested by flow cytometry result: software analysis result 10
4CD31 (+) cell accounts for 94.04% of sum in the individual cell, and vWF (+) cell accounts for 1.1%, shows that cultivating endotheliocyte purity is 94.04%, meets capable gene chip detection cell requirement.VWF (+) cell accounts for 10
4In the cell 1.1%, may be to sneak into a small amount of arterial endothelium in the incubation to cause, but the arterial cell endothelium influence this experimentation for number is few.
Two, cell growth curve and cell viability are measured
The result as shown in Figure 6, the endothelial cell growth curve shows that second filial generation endotheliocyte is logarithmic growth, meets this requirement of experiment.
Three, Chinese medicine preparation of the present invention is cultivated the endothelial cell proliferation influence to the 20mmol/L glucose
1. different disposal is cultivated 24 hour cell count results as shown in Figure 7.
2. respectively organize the cell growing state under the light microscopic shown in Fig. 8-15.
Relatively under the 5mmol/L concentration of glucose, initial incubation and cultivated endothelial cell morphology in 24 hours found that cellular morphology do not have significant change (Fig. 8 and 9).
Relatively under the 20mmol/L concentration of glucose, initial incubation and 24 hours cultivation endothelial cell morphology found that 20mmol/L glucose cultivation back cell distribution is sparse, do not become typical paving stone sample to arrange, and cell number reduces (Figure 10 and 11).
Relatively the 20mmol/L glucose adds the Chinese medicine initial incubation and cultivated endotheliocyte in 24 hours, found that two groups of cellular morphologies, numbers do not have obvious change (Figure 12 and 13).
Relatively the 20mmol/L glucose adds the NAC initial incubation and cultivated endotheliocyte in 24 hours, found that two groups of cellular morphologies, numbers do not have obvious change (Figure 14 and 15).
Relatively the 5mmol/L glucose is cultivated 24 hours (Fig. 9), the cultivation of 20mmol/L glucose 24 hours (Figure 11), 20mmol/L glucoses add Chinese medicine cultivation 24 hours (Figure 13), 20mmol/L glucoses and add 24 hours endotheliocyte images (Figure 15) of NAC cultivation, find that acute high sugar obviously suppresses endothelial cell growth, Chinese medicine and NAC can recover the inhibitory action of high sugar to endothelial cell growth.
Conclusion
One, acute high sugar (20mmol/L, 24 hours) injury rats PMEC (Pulmonary Microvascular Endothelial Cells).
Two, (oral liquid a) can recover impaired capillary endothelium to Chinese medicine preparation of the present invention.
Test implementation example 3
Different Chinese medicine preparation are to the influence of endotheliocyte multiplication capacity
The method of retest embodiment 2, difference only are with oral liquid b, c, d, e, f, g, h, i, j, k.
The result shows that these oral liquids can make acute high sugar (20mmol/L, 24 hours) injury rats PMEC (Pulmonary Microvascular Endothelial Cells) recovery down equally.Relative activity with oral liquid a is 100%, and the relative property of each oral liquid is as follows:
| Oral liquid | Relative activity (%) |
| a | 100 |
| b | 95 |
| c | 93 |
| d | 98 |
| e | 87 |
| f | 105 |
| g | 110 |
| h | 95 |
| i | 97 |
| j | 93 |
| k | 90 |
Discuss
At present, except positive blood sugar control, blood pressure, the multiple factor of blood fat, the medicine that is used for the treatment of diabetic complication specifically is still rare.The tradition traditional Chinese medical science has the experience prescription of a lot of treatment diabetic complications, but rare bibliographical information levies medical science and estimated with following, and the mechanism of action of Chinese medicine is known little about it.The traditional Chinese medical science blood circulation promoting and blood stasis dispelling rule of treatment has comprised the effect of anti-endothelial injury, anti-high blood coagulation at diabetic complication, and the heat-clearing and toxic substances removing rule of treatment may have antiinflammatory action.The used Chinese medicine preparation of the present invention is in conjunction with the prescription of blood circulation promoting and blood stasis dispelling, the heat-clearing and toxic substances removing two big rule of treatment, is intended to vascular complication is played intervention effect, and therapeutic goal is clear and definite, and curative effect is reliable, and better tolerance has clear and definite clinical value.
The clinical part of the present invention takes the lead in the GCP method is applied to Chinese medicinal formulae research at home.Adopt contrast at random, single blind, the clinical trial of placebo parallel control is made comparatively objective appraisal for Chinese medicine preparation curative effect of the present invention, is better than general Chinese medicine clinical research.The clinical part of the present invention has been chosen UAER as one of MAIN OUTCOME MEASURES, can reflect the microangiopathies order of severity to a certain extent, has also reflected endothelial injury widely simultaneously.Nail fold microcirculation is another MAIN OUTCOME MEASURES of the present invention, and the first folds in a garment is that noinvasive is observed microcirculatory optimal site, and wherein vascular morphology and hemorheologic parameters can reflect finger tip microcirculation situation, also reflect the endothelial injury degree to a certain extent.Endothelial injury can be more comprehensively represented in UAER and nail fold microcirculation, the degree of vascular complication, thereby objective evaluation curative effect of medication.
Base component of the present invention has been carried out preliminary discussion for the mechanism of Chinese medicine preparation effect of the present invention.By observing the variation of endothelial cell proliferation ability before and after the medication under the sugared environment of external height, can objectively respond the protective effect of Chinese medicine preparation of the present invention to endothelial injury.And, proved that Chinese medicine preparation of the present invention has antioxidation further by comparing with the effect of antioxidant NAC.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (11)
1. compositions that is used for the treatment of diabetic complication, it is characterized in that, it contains (a) pharmaceutically acceptable carrier and (b) by the water extract of the raw medicinal material of composition total weight 1-90% or the extract of aqueous organic solvent, and the dry weight of pressing medical material is calculated, every gram solid composite or every milliliter of fluid composition are corresponding to the total dried medical material that contains the 0.1-10 gram, wherein, described raw medicinal material is by Rhizoma Chuanxiong, Hirudo, the Radix Astragali, Radix Puerariae, Gardenia, Herba Artemisiae Scopariae, Herba Pteridis Multifidae, constitute with Pericarpium Citri Reticulatae
And the parts by weight of described raw medicinal material are as follows:
Rhizoma Chuanxiong 90
Hirudo 36
The Radix Astragali 180
Radix Puerariae 60
Gardenia 90
Herba Artemisiae Scopariae 90
Herba Pteridis Multifidae 90
Pericarpium Citri Reticulatae 36
Perhaps, the parts by weight of described raw medicinal material are as follows:
Rhizoma Chuanxiong 4
Hirudo 3
The Radix Astragali 15
Radix Puerariae 6
Gardenia 9
Herba Artemisiae Scopariae 9
Herba Pteridis Multifidae 9
Pericarpium Citri Reticulatae 10.
2. compositions as claimed in claim 1 is characterized in that, described raw medicinal material is replaced by the raw medicinal material that is made of the following medical material of parts by weight:
Rhizoma Chuanxiong 4
Hirudo 3
The Radix Astragali 15
Radix Puerariae 6
Gardenia 9
Herba Artemisiae Scopariae 9
Herba Pteridis Multifidae 9
Pericarpium Citri Reticulatae 10
Rhizoma Phragmitis 15
Herba Lophatheri 30
Flos Lonicerae 15
Herba Violae 30
Herba Lobeliae Chinensis 30
Herba Scutellariae Barbatae 30.
3. compositions as claimed in claim 1 is characterized in that, described raw medicinal material is replaced by the raw medicinal material that is made of the following medical material of parts by weight:
Rhizoma Chuanxiong 4
Hirudo 3
The Radix Astragali 15
Radix Puerariae 6
Gardenia 9
Herba Artemisiae Scopariae 9
Herba Pteridis Multifidae 9
Pericarpium Citri Reticulatae 10
Semen Persicae 5
Myrrha 2
Radix Salviae Miltiorrhizae 5
Rhizoma Phragmitis 5
Flos Lonicerae 6
Herba Violae 8.
4. compositions as claimed in claim 1 is characterized in that, described raw medicinal material is replaced by the raw medicinal material that is made of the following medical material of parts by weight:
Rhizoma Chuanxiong 4
Hirudo 3
The Radix Astragali 15
Radix Puerariae 6
Gardenia 9
Herba Artemisiae Scopariae 9
Herba Pteridis Multifidae 9
Pericarpium Citri Reticulatae 10
Semen Persicae 10
Flos Carthami 9
Olibanum 9
Myrrha 9
Caulis Spatholobi 15
Radix Salviae Miltiorrhizae 15.
5. compositions as claimed in claim 1 is characterized in that, described raw medicinal material is replaced by the raw medicinal material that is made of the following medical material of parts by weight:
Rhizoma Chuanxiong 4
Hirudo 3
The Radix Astragali 15
Radix Puerariae 6
Gardenia 9
Herba Artemisiae Scopariae 9
Herba Pteridis Multifidae 9
Pericarpium Citri Reticulatae 10
Flos Carthami 3
Olibanum 3
Caulis Spatholobi 5
Herba Lophatheri 10
Herba Lobeliae Chinensis 10
Herba Scutellariae Barbatae 10.
6. compositions according to claim 1 is characterized in that described compositions is tablet, capsule or granule.
7. compositions as claimed in claim 1 is characterized in that, described compositions is an oral liquid.
8. compositions as claimed in claim 1 is characterized in that, presses the dry weight of medical material and calculates, and every gram solid composite or every milliliter of fluid composition are corresponding to the total dried medical material that contains the 0.2-5 gram.
9. one kind prepares arbitrary described method for compositions among the claim 1-8, it is characterized in that, comprises step:
(a) with the water of described medical material and 1-20 times of weight or the mixture of aqueous solvent, decocted 1-6 hour to the boiling condition at 80 ℃, obtain mixed liquor;
(b) filter mixed liquor, obtain filtrate,
(c) the filtrate volume is concentrated 5-50 doubly, obtain concentrated solution, i.e. extract;
(d) extract is mixed with pharmaceutically acceptable carrier, form compositions.
10. method as claimed in claim 9 is characterized in that, also comprises step in step (c) with (d): the concentrated solution that obtains is carried out drying, thereby obtain the solids extraction thing; Perhaps
Also comprise step in step (c) with (d): the concentrated solution that obtains is mixed with the 70-99% ethanol of 1-10 times of volume, place after 12-72 hour, reclaim the supernatant that contains alcohol, filter and obtain filtrate.
11. the purposes of arbitrary described compositions is characterized in that among the claim 1-8, is used to prepare the medicine for the treatment of diabetic vascular complications.
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