CN103520538B

CN103520538B - A kind ofly treat the pharmaceutical composition that diabetes cause kidney damage

Info

Publication number: CN103520538B
Application number: CN201310480081.5A
Authority: CN
Inventors: 刘渊; 孙晓峰; 钟学文
Original assignee: Individual
Current assignee: Liu Yuan
Priority date: 2013-10-15
Filing date: 2013-10-15
Publication date: 2015-08-05
Anticipated expiration: 2033-10-15
Also published as: CN103520538A

Abstract

The invention discloses and a kind ofly treat the pharmaceutical composition that diabetes cause kidney damage, to solve the treatment problem of diabetic nephropathy.It is characterized in that being prepared from by the crude drug of following weight proportion: Fructus Cannabis, certain herbaceous plants with big flowers colza, Flos Magnoliae Amoenae, Cortex Ponciri trifoliatae, Herba Taxilli, Bulbus Allii Victorialis, go back bobbin, Radix Ranunculi Ternati, Caulis Trachelospermi, Cortex erythrinae, Ramulus Cinnamomi, Fructus Setariae Germinatus (parched to brown).Clinical trial certificate: the present invention treats diabetic nephropathy and has good effect and the higher feature of safety, clinic application, promotes.

Description

A kind ofly treat the pharmaceutical composition that diabetes cause kidney damage

Technical field

The present invention relates to the field of Chinese medicines, be specifically related to a kind ofly treat the pharmaceutical composition that diabetes cause kidney damage.

Background technology

Foreign literature is reported, microalbuminuria occurs the course of disease type i diabetes patient 40% ~ 50% of 10 ~ 15 years, and the result of the research simultaneously also shows: type ii diabetes also has 20% ~ 30% diabetic nephropathy occurs at viewing duration.So-called diabetic nephropathy (diabetic nephropathy, DN), be one of most important complication of diabetic, also in rising trend at the sickness rate of China in recent years, become the second reason of End-stage renal disease at present, be only second to various glomerulonephritis.Because it exists complicated metabolism disorder, once develop into End-stage renal disease, often more thorny than the treatment of other kidney diseases, therefore control is in time for delaying the significant of diabetic nephropathy.

The current diabetic nephropathy cause of disease and pathogenesis still unclear.Inventor's clinical research for many years finds, the effect of the Developmental and Metabolic Disorder that hyperglycemia causes in diabetic nephropathy pathogenesis is particularly outstanding, wherein Developmental and Metabolic Disorder causes the mechanism of kidney damage mainly to comprise: 1. nephridial tissue local carbohydrate metabolism disturbance, forms advanced glycosylation endproduct end metabolite (AGES) by nonenzymatic glycosylation; 2. the activation of polyhydric alcohol path; The activation of 3. DG-protein kinase c approach; 4. osamine path Developmental and Metabolic Disorder.Above-mentioned Developmental and Metabolic Disorder is except participating in early stage high filtration, and what is more important promotes that glomerular basement membrane (GBM) thickens and extracellular matrix accumulation.

Because the cause of disease is unclear, so diabetic kidney injury clinical treatment is mainly symptomatic treatment: 1. control blood glucose; 2. blood pressure is controlled; 3. dietetic therapy.The diabetic complication of diabetic nephropathy patients undergoing itself is common, and symptoms of uremia occurs comparatively early, and general endogenous creatinine clearance rate is down to 10 ~ 15ml/min will maintenance dialysis, patient economy burden weight.The traditional Chinese medical science is then recorded without primary disease, and treatment is many to duplicate with diabetes, and opinion is controlled from the scorching deficiency of YIN, with the passing of time consumption gas and cause deficiency of both QI and YIN, PD then deficiency of YIN affecting YANG and see deficiency of both YIN and YANG, and even sun declines turbid malicious stasis blocking.Owing to not fully taking into account the effect of Developmental and Metabolic Disorder in diabetic nephropathy pathogenesis that hyperglycemia causes, so current Chinese traditional treatment there is no help for delaying kidney damage.

Summary of the invention

Technical assignment of the present invention is for above the deficiencies in the prior art, provides a kind of curative effect certainly and the little treatment diabetes of side effect cause the pharmaceutical composition of kidney damage.

The technical scheme that the present invention solves its technical problem is: a kind ofly treat the pharmaceutical composition that diabetes cause kidney damage, it is characterized in that being prepared from by the crude drug of following weight proportion: Fructus Cannabis 10 ~ 30 parts, certain herbaceous plants with big flowers colza 6 ~ 12 parts, Flos Magnoliae Amoenae 3 ~ 10 parts, Cortex Ponciri trifoliatae 6 ~ 12 parts, Herba Taxilli 3 ~ 10 parts, Bulbus Allii Victorialis 6 ~ 12 parts, go back 6 ~ 12 parts, bobbin, Radix Ranunculi Ternati 6 ~ 12 parts, Caulis Trachelospermi 6 ~ 12 parts, Cortex erythrinae 1 ~ 5 part, Ramulus Cinnamomi 3 ~ 10 parts, Fructus Setariae Germinatus (parched to brown) 10 ~ 25 parts.

Chinese medicine of the present invention is prepared from by the raw material of following optimum weight part proportioning: Fructus Cannabis 20 parts, certain herbaceous plants with big flowers colza 10 parts, Flos Magnoliae Amoenae 6 parts, Cortex Ponciri trifoliatae 10 parts, Herba Taxilli 6 parts, Bulbus Allii Victorialis 10 parts, go back 10 parts, bobbin, Radix Ranunculi Ternati 10 parts, Caulis Trachelospermi 10 parts, Cortex erythrinae 2 parts, Ramulus Cinnamomi 6 parts, Fructus Setariae Germinatus (parched to brown) 20 parts.

Wherein said: Fructus Cannabis is the dry mature fruit of moraceae plants Fructus Cannabis Cannabis sativa L..Nature and flavor are sweet, flat.Return spleen, stomach, large intestine channel.Merit can loosening bowel to relieve constipation.

Certain herbaceous plants with big flowers colza is the mature seed of Malvaceae herbaceous plant Semen Abutili AbutilontheophrastiiMedic.Nature and flavor are sweet, cold.Return large intestine, small intestine meridian.Merit can clearing away heat and promoting diuresis treating stranguria, lactogenesis, intestine moistening.

Flos Magnoliae Amoenae, is Magnoliaceae head Drymotaenium miyoshianum (Mak.) Mak. Magnolia amoena Cheng, is used as medicine with alabastrum.Nature and flavor are bitter, cold.Merit can diuresis, detumescence, nourishing the lung to arrest cough.

Cortex Ponciri trifoliatae is bark bits or the peel bits of rutaceae Fructus Ponciri Trifoliatae (Fructus Ponciri Trifoliatae Immaturus) Poncirus tuifoliata (L.) Raf..Nature and flavor are pungent; Temperature.Return liver; Kidney channel.Merit can endogenous wind stopping relieving convulsion; Eleminating phlegm and freeing channels.

Herba Taxilli, for Herba Taxilli is the dry stem and branch with leaf of Loranthaceae plant Herba Taxilli Taxillus chinensis (DC.) Danser.Nature and flavor bitter, sweet, flat.Return liver, kidney channel.Merit can invigorating the liver and kidney, bone and muscle strengthening, wind-damp dispelling, antiabortive unit.

Bulbus Allii Victorialis is the bulb of liliaceous plant Bulbus Allii Victorialis Allium victorialis L..Return lung meridian.Merit can dissipating blood stasis; Hemostasis; Removing toxic substances.

Also bobbin is the fruit of orchid Rhizoma Gastrodiae Gastrodia elata Bl..Sweet in the mouth; Cold in nature.Merit can tonify deficiency subduing the wind syndrome.

Radix Ranunculi Ternati is the dried root of ranunculaceae plant Seynuns Kugelann Ranunculus ternatus Thunb..Nature and flavor sweet, acrid, warm.Return liver, lung meridian.Merit can eliminating stagnation, detumescence.

Caulis Trachelospermi is the dry zone leaf rattan of apocynaceae plant trachelospermum jasminoide Trachelospermum jasminoides (Lindl.) Lem..Hardship, is slightly cold.Return kidney, liver, kidney channel.Merit can dispelling wind and removing obstruction in the collateral, and removing heat from blood is subsided a swelling.

Cortex erythrinae is bark or the root bark of pulse family Erythrinae Arborescentis Erythrina indica Lam..Nature and flavor are bitter, flat.Return liver, kidney channel.Merit can wind-damp dispelling, channels sootheing and network vessel quickening.Wind-damp dispelling, the meridian dredging, parasite killing.

Ramulus Cinnamomi is the withe of canella Cortex Cinnamomi Cinnamomum cassia Presl.Nature and flavor acrid, sweet, warm.Enter the heart, lung, urinary bladder channel.Merit can relieving the exterior syndrome by diaphoresis, promoting the flow of QI-blood by warming the meridian, activating YANG and prormoting functioning of QI.

Fructus Setariae Germinatus (parched to brown), for the mature fruit of grass foxtail millet Setaria italica (L.) Beauv. is through drying of germinateing, fries to burnt brown according to frying method.Nature and flavor are sweet, temperature.Return spleen, stomach warp.Merit can help digestion and in, spleen benefiting and stimulating the appetite.

Clinical the past research shows, DN is mainly present in type i diabetes, and natural history starts for 10 ~ 15 years, and type i diabetes patient starts to occur continuous micro albuminuria, and glomerule nodule-like lesions and small artery vitreous degeneration appear in Pathological.The basis of this pathological change is that hyperglycemia causes Developmental and Metabolic Disorder, promotes that glomerular basement membrane (GBM) thickens and extracellular matrix accumulation.At present, Chinese traditional treatment is not for the medicine typing of DN, and treatment is many to duplicate with diabetes, and opinion is controlled from the scorching deficiency of YIN, with the passing of time consumption gas and cause deficiency of both QI and YIN, PD then deficiency of YIN affecting YANG and see deficiency of both YIN and YANG, and even sun declines turbid malicious stasis blocking.Owing to not fully taking into account the effect of Developmental and Metabolic Disorder in diabetic nephropathy pathogenesis that hyperglycemia causes, so there is no help for delaying kidney damage.

Inventor thinks: existing traditional Chinese medical therapeutic program is many starts with from the deficiency of YIN; but ignore another pathological factor " expectorant coagulates " of primary disease; the diabetes that various pathological factors causes controls protracted course of disease for a long time; deficiency in both YIN and YANG; QI and blood is not all right; expectorant coagulates venation, then water-damp not being transformed of a specified duration, stops giving birth to him in long-pending body and becomes.So inventor starts with from this angle, carry out the innovation on prescription.

Compared with prior art, the present invention has following characteristics:

1, set forth one's views unique: controlling from " QI and blood is not all right, and expectorant coagulates venation " opinion diabetic nephropathy, is that tangible heresy blocks kidney network, causes kidney network not all right and his change raw, so get rid of evils as key element.But the pathologic basis of DN is again deficiency in both YIN and YANG, and simulataneous insufficiency and excessive, needs strengthening vital QI to eliminate pathogenic factors.

2, with Fructus Cannabis, certain herbaceous plants with big flowers colza for monarch: inventor's clinical experience gained, Fructus Cannabis, certain herbaceous plants with big flowers colza are good at except the visible phlegm among venation, and without the anxiety of impairment of YIN, are suitable for DN and use; And Basic pharmacology test confirms: compare with GBM nephritis blank group after rats underwent Fructus Cannabis (20g crude drug/kg/d) and certain herbaceous plants with big flowers colza (10g crude drug/kg/d) mixing water decocting liquid gavage 4w after injection nephrolytic sera, Rat 24 h urine protein level is only 43.33% of blank group.

3, monarch drug is assisted using Flos Magnoliae Amoenae inducing diuresis to remove edema, Caulis Trachelospermi dispelling wind dredging collateral, Cortex Ponciri trifoliatae eleminating phlegm and freeing channels, Bulbus Allii Victorialis dissipating blood stasis, Radix Ranunculi Ternati mass dissipating and swelling eliminating as ministerial drug: accumulation of phlegm blocks, breath does not reach, of a specified duration then can produce blood stasis, the stasis of blood then water retention of a specified duration, so select the visible phlegm in Cortex Ponciri trifoliatae, Flos Magnoliae Amoenae removal the kidney pulse network, Caulis Trachelospermi, Radix Ranunculi Ternati increase the ability of medicine walking venation.Bulbus Allii Victorialis has the advantages that dissipating blood stasis does not consume gas, and Flos Magnoliae Amoenae diuretic not impairment of YIN, this two herbal medicine is particularly suitable for the treatment of DN deficiency in both YIN and YANG and uses.

4, with Herba Taxilli tonifying the lung Liver and kidney, go back the righting of bobbin tonify deficiency subduing the wind syndrome, it is loose that low dose of its activating YANG and prormoting functioning of QI of Ramulus Cinnamomi contributes to row.

5, low dose of Cortex erythrinae is the gas of damp in stern kidney channel meridians, and power is high so measure micro-.

6, Fructus Setariae Germinatus (parched to brown) is sweet in flavor and warm in property, returns taste warp, in one cold and cool medicine, get protect sun defend in meaning, and contained coking composition has astriction, has the meaning of receipts in loose.

7, the homogeneous medicine multiple-effect of institute's thing of getting it filled in side, contributes to reducing medicament categories and consumption, does not increase Liver and kidney burden.

8, medicine material consumption of the present invention is groped to sum up to draw through inventor in a large number, and each raw material dosage is for all to have good curative effect in following weight parts scope.

Detailed description of the invention

Below in conjunction with practical situation, the specific embodiment of the present invention is elaborated.

Embodiment 1, crude drug weight proportion: Fructus Cannabis 20g, certain herbaceous plants with big flowers colza 10g, Flos Magnoliae Amoenae 6g, Cortex Ponciri trifoliatae 10g, Herba Taxilli 6g, Bulbus Allii Victorialis 10g, go back bobbin 10g, Radix Ranunculi Ternati 10g, Caulis Trachelospermi 10g, Cortex erythrinae 2g, Ramulus Cinnamomi 6g, Fructus Setariae Germinatus (parched to brown) 20g.

The preparation method of embodiment 1 is: by Fructus Cannabis, certain herbaceous plants with big flowers colza, Flos Magnoliae Amoenae, Cortex Ponciri trifoliatae, Herba Taxilli, Bulbus Allii Victorialis, go back bobbin, Radix Ranunculi Ternati, Caulis Trachelospermi, Cortex erythrinae, Ramulus Cinnamomi, the decoction of Fructus Setariae Germinatus (parched to brown) mixing and water adding, filtrate is got after 30 minutes, medicinal residues add water continue decoction get filtrate after 20 minutes, twice filtrate merges, and is divided into two parts of morning and evenings to take.

Embodiment 2, crude drug weight proportion: Fructus Cannabis 10 parts, certain herbaceous plants with big flowers colza 6 parts, Flos Magnoliae Amoenae 3 parts, Cortex Ponciri trifoliatae 6 parts, Herba Taxilli 3 parts, Bulbus Allii Victorialis 6 parts, go back 6 parts, bobbin, Radix Ranunculi Ternati 6 parts, Caulis Trachelospermi 6 parts, Cortex erythrinae 1 part, Ramulus Cinnamomi 3 parts, Fructus Setariae Germinatus (parched to brown) 10 parts.

Embodiment 3, crude drug weight proportion: Fructus Cannabis 20 parts, certain herbaceous plants with big flowers colza 10 parts, Flos Magnoliae Amoenae 6 parts, Cortex Ponciri trifoliatae 10 parts, Herba Taxilli 6 parts, Bulbus Allii Victorialis 10 parts, go back 10 parts, bobbin, Radix Ranunculi Ternati 10 parts, Caulis Trachelospermi 10 parts, Cortex erythrinae 2 parts, Ramulus Cinnamomi 6 parts, Fructus Setariae Germinatus (parched to brown) 20 parts.

Embodiment 4, crude drug weight proportion: Fructus Cannabis 30 parts, certain herbaceous plants with big flowers colza 12 parts, Flos Magnoliae Amoenae 10 parts, Cortex Ponciri trifoliatae 12 parts, Herba Taxilli 10 parts, Bulbus Allii Victorialis 12 parts, go back 12 parts, bobbin, Radix Ranunculi Ternati 12 parts, Caulis Trachelospermi 12 parts, Cortex erythrinae 5 parts, Ramulus Cinnamomi 10 parts, Fructus Setariae Germinatus (parched to brown) 25 parts.

The Chinese medicine of embodiment 2 ~ 4 can be prepared from by following method:

(1) bobbin will be gone back, certain herbaceous plants with big flowers colza, Herba Taxilli coarse powder soak separately after 4 hours and extract volatile oil 6 hours with vapor distillation, and mixing for standby use after collecting, medicinal residues are for subsequent use;

(2) Cortex erythrinae, Fructus Setariae Germinatus (parched to brown) are pulverized 150 mesh sieves, and become fine powder for subsequent use;

(3) by gained medicinal residues mixing in Fructus Cannabis, Flos Magnoliae Amoenae, Cortex Ponciri trifoliatae, Bulbus Allii Victorialis, Radix Ranunculi Ternati, Caulis Trachelospermi, Ramulus Cinnamomi and step 1 with 5 times amount 80% ethanol extraction 2 times, each 2 hours, merge twice ethanol extract, filter, reclaiming relative density when ethanol concentrating under reduced pressure become 60 DEG C is the extractum of 1.25 ~ 1.30;

(4) gained fine powder in step 2 is added gained extractum mixing in step 3,60 DEG C of oven dry, are ground into fine powder, add Tween-80 and make granule, and dry, granulate, sprays into gained volatile oil in step 1, and mixing, incapsulates, to obtain final product.

Can set every capsules is 0.5g.

The efficient combination of said medicine, coordinates mutually, effectively reach the object for the treatment of diabetic nephropathy, and side effect is less.The above results is clinical data sufficient proof, and interrelated data is as follows.

1 object and method.

1.1 object.

1.1.1 case selection: case is selected from June, 2006 ~ 2011 and is diagnosed as early diabetic nephropathy 100 example year June.

1.1.2 diabetic nephropathy diagnostic criteria: diagnosis all meets ADA's formulation standard in 1997, namely the diagnostic criteria of early stage DN is: (1) diabetes medical history, and occurs persistence Microalbuminuria (UAER reaches 20 ~ 200/ μ g/min or 30 ~ 300 mg/d); (2) glomerular filtration rate (GRF) rises more than 20%; (3) conventional UAER detects negative.Except standard: (1) severe hypertension; (2) severe infection or other diseases; (3) BAOSHENKANG is used during person; (4) kidney disease of other reasons.

1.1.3 three groups are divided at random: matched group 35 example, decoction group 33 example, Capsules group 32 example.Compare in sex, age, the state of an illness, the course of disease before three groups of patient treatments, no significant difference (P>0.05), has comparability.

1.2 method.

1.2.1 Therapeutic Method: three groups of patients all adopt standard diabetic+high-quality Low protein and low phosphorus diet, is strict with less salt and ankyrin, diet control blood glucose and blood pressure medication, and decoction group adds with embodiment 1 gained decoction on matched group medication basis, 2 times/d; Capsules group adds described embodiment 3 gained capsule 2g/ time on matched group medication basis, 2 times/d, totally 30 d.All patients all do not adopt ACEI and/or ARB class Drug therapy and intestinal dialysis, hemodialysis and peritoneal dialysis treatment.

1.2.2 observation item: the front and rear change observing three groups of patient 24 h urine protein quantitation (TP/24 h), glomerular filtration rate (GFR), cholesterol (TC), triglyceride (TG) for the treatment of respectively at treatment, and the change of ALT, AST.

1.2.3 statistical analysis: SPSS 13.0 carries out statistical analysis.Measurement data t checks, enumeration data χ ²inspection.

2 results.

The change of three groups of patient TP/24 h, GFR, TC, TG after 2.1 treatment 30d: see the following form.Result shows: treat after 30 days, the level of the 24 h urine protein quantitation (TP/24 h) of decoction group and Capsules group, glomerular filtration rate (GFR), cholesterol (TC), triglyceride (TG) obviously reduces (P<0.05) before comparatively treating, simultaneously also lower than matched group with time point level (P<0.05).

2.2 3 groups of adverse reactions of patients incidence rates compare: decoction group has 15.15%(5/33), Capsules group has 9.38%(3/32) there is transient diarrhoea in patient, alleviate after anti symptom treatment, non-drug withdrawal.In addition, three groups all there is not obvious adverse reaction record, and before and after treatment, ALT, AST level has no significant change.

3. conclusion.

This result of study shows, after taking decoction of the present invention or capsule, diabetic nephropathy patient TP/24 h, GFR, TC, TG are starkly lower than matched group, and there is not obvious adverse reaction record, illustrate that pharmaceutical composition of the present invention has the lighter advantage of good effect, untoward reaction in treatment diabetic nephropathy.

Claims

1. treat the pharmaceutical composition that diabetes cause kidney damage, it is characterized in that being prepared from by the crude drug of following weight proportion: Fructus Cannabis 10 ~ 30 parts, certain herbaceous plants with big flowers colza 6 ~ 12 parts, Flos Magnoliae Amoenae 3 ~ 10 parts, Cortex Ponciri trifoliatae 6 ~ 12 parts, Herba Taxilli 3 ~ 10 parts, Bulbus Allii Victorialis 6 ~ 12 parts, go back 6 ~ 12 parts, bobbin, Radix Ranunculi Ternati 6 ~ 12 parts, Caulis Trachelospermi 6 ~ 12 parts, Cortex erythrinae 1 ~ 5 part, Ramulus Cinnamomi 3 ~ 10 parts, Fructus Setariae Germinatus (parched to brown) 10 ~ 25 parts.

2. according to claim 1ly a kind ofly treat the pharmaceutical composition that diabetes cause kidney damage, it is characterized in that being prepared from by the crude drug of following weight proportion: Fructus Cannabis 20 parts, certain herbaceous plants with big flowers colza 10 parts, Flos Magnoliae Amoenae 6 parts, Cortex Ponciri trifoliatae 10 parts, Herba Taxilli 6 parts, Bulbus Allii Victorialis 10 parts, go back 10 parts, bobbin, Radix Ranunculi Ternati 10 parts, Caulis Trachelospermi 10 parts, Cortex erythrinae 2 parts, Ramulus Cinnamomi 6 parts, Fructus Setariae Germinatus (parched to brown) 20 parts.