CN101234136B - Medicament for curing diabetes retina affection - Google Patents
Medicament for curing diabetes retina affection Download PDFInfo
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- CN101234136B CN101234136B CN2008100071887A CN200810007188A CN101234136B CN 101234136 B CN101234136 B CN 101234136B CN 2008100071887 A CN2008100071887 A CN 2008100071887A CN 200810007188 A CN200810007188 A CN 200810007188A CN 101234136 B CN101234136 B CN 101234136B
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- radix rhodiolae
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Abstract
The invention discloses a medicine for treating diabetic retinopathy, which is prepared to be an oral drug with red common stonecrop herb as a control effect raw material and can be added in RhizomaChuanxiong, Salvia miltiorrhiza Bge and Glycyrrhiza to be prepared into any suitable dosage forms. The animal experiment shows that the medicine can reduce the positive expression of vascular endothelial growth factor (VEGF) of a rat retina tissue, which displays significance for treating diabetic retinopathy.
Description
Technical field
The present invention relates to the Chinese medicinal plant medicine is the medicine that raw material is made, and particularly is the medicine of the treatment of diabetic retinopathy change of main pharmacodynamics preparation of raw material with the Radix Rhodiolae.
Background technology
Diabetic renal papillary necrosis (diabetic retinopathy) is one of severe complication of diabetes, is important diseases causing blindness.Laser light is that present treatment of diabetic retinopathy becomes the method for the most generally using with fixed attention, but light coagulates therapy severe complication takes place easily, as light coagulate that rearward vision is damaged, vitreous hemorrhage, macular edema, detachment of retina, iritis and cataract increases the weight of, cicatrix expansion, decrease of contrast sensitivity etc. are coagulated in fibroplasia under the accidental injury central fovea of macula, SRNM, retina, light.
Modern medicine is the etiological treatment that thickens etc. diabetic microvascular complication at capillary basement membrane to the treatment of diabetic renal papillary necrosis.Yet, the carbohydrate metabolism disturbance of diabetics causes a series of biochemistry of whole body, physiology, pathological reaction, numerous factors are all relevant with generation, the development of patient's retinopathy, even if a certain medicine has good action to a certain link in the cause of disease, also difficulty is received good efficacy on the whole.So still there be not a kind of chemistry or bio-pharmaceutical that effective treatment of diabetic retinopathy becomes that be acknowledged as at present.
Chinese traditional medicine is also very extensive to the research that treatment of diabetic retinopathy becomes, some medicines or prescription have been reported the effect that some is useful at aspects such as improving retinopathy and clinical symptoms, blood sugar lowering, adjustment lipid metabolism, immunomodulating, hematodinamics, free radical activity, glycolated hemoglobin, erythrocyte sod activity, but many researchs or case select and criterion of therapeutical effect aspect owing standard, perhaps experimental design is unreasonable, perhaps sample is very few, and its result still is not enough to illustrate their superioritys with respect to the similar medicine that has gone on the market.The method of primary disease being implemented activating blood and resolving stasis and treating by theory of Chinese medical science gains universal acceptance, but its curative effect also is limited, and grasp does not with great difficulty cause repeatedly hemorrhage.
The Chinese medicine Radix Rhodiolae is a kind of medicinal herbs most in use, and the constituent of Chang Zuowei resisting fatigue prescription also is useful on treatment coronary heart disease, but does not still have the record of Radix Rhodiolae treatment retinopathy.
Summary of the invention
The present invention aims to provide the medicine that a kind of treatment of diabetic retinopathy becomes, and it is simple for production, and taking convenience is reliable for effect.
The medicine that treatment of diabetic retinopathy of the present invention becomes is that pharmacodynamic raw materials is made with Chinese medicine Radix Rhodiolae (Rhodioladumulosa).In the segmentation kind of Radix Rhodiolae, (Rhodiola sachalinensisA.Bor) is excellent with Radix Rhodiolae, again to originate in the most suitable making of the Radix Rhodiolae medicine of the present invention on Chinese Changbai Mountain.
As optimization, to make pharmacodynamic raw materials that treatment of diabetic retinopathy of the present invention becomes medicine and also comprise Rhizoma Chuanxiong and Radix Salviae Miltiorrhizae, Radix Glycyrrhizae three medicines, the consumption proportion of they and Radix Rhodiolae is expressed as by weight, Radix Rhodiolae 10-15, Rhizoma Chuanxiong 10-15, Radix Salviae Miltiorrhizae 10-15, Radix Glycyrrhizae 10-15.
Use the best proportioning weight portion that this four Chinese medicine is imitated raw material to be Radix Rhodiolae 10, Rhizoma Chuanxiong 10, Radix Salviae Miltiorrhizae 10, Radix Glycyrrhizae 10.
The employed pharmacodynamic raw materials Radix Rhodiolae of medicine of the present invention is Crassulaceae rhodiola (Rhodiola L) herbaceos perennial, and its main effective ingredient is rhodioloside (D
4H
20O
7) and Jujubogenin tyrosol and benzhydryl pyridinium hydroxide.Rhodioloside can increase the flowability of blood monocytes and tunica intima macrophage, reduces cholesterol and deposits at blood vessel, promotes the endothelium relaxing factor to discharge, and stops platelet aggregation, microcirculation improvement; Rhodioloside and Jujubogenin tyrosol have resisting fatigue, anti-hypoxia, resisting microwave radiation, antitoxin and to the effect of nervous system and metabolism two-ways regulation; Radix Rhodiolae is rich in 18 seed amino acids, 35 kinds of inorganic elementss, and wherein 15 kinds is the magnanimity or the trace element of needed by human; Radix Rhodiolae also contains vitamin A, C, D, E, B
1, B
2, B
6, containing bioactive substances such as the superoxide dismutase have activity of fighting against senium in a large number and pyrite class, Coumarins, scopoletin, rutin, nutritive value is high.
The traditional Chinese medical science thinks that Radix Rhodiolae has mediation blood vessels, removing heat from blood, invigorating blood circulation effect, attaches most importance to the flavor of strengthening by means of tonics, can the kidney invigorating add essence greatly, makes water contain wood, and easing the affected liver relieves dizziness, high fever, infantile convulsions, epilepsy, etc., and moistens nourishing the liver and kidney, blood circulation-activating eyesight-improving, a medicine and Liver and kidney two accent.
The present invention selects for use Radix Rhodiolae to make pharmacodynamic raw materials and has utilized its above-mentioned pharmacological action just.
Simultaneously, acute and sub-acute toxicity experiment shows that Radix Rhodiolae toxicity is very low, no teratogenesis mutagenic action.
In medicine optimization of C of the present invention, Rhizoma Chuanxiong (Ligusticum chunxiong Hort) is a drug for invigorating blood circulation and eliminating stasis, and its gas fragrance is dry strong, and the kind top Top that scurries is the gas medicine in the blood, and the present invention makes ministerial drug with it, complements each other with Radix Rhodiolae.Modern pharmacological research shows that Rhizoma Chuanxiong suppresses platelet activation, makes thromboxane A in the circulation blood
2(TXA
2) and prostacyclin (PGI
2) the maintenance balance; Improve three indexs of whole blood viscosity; The blood oxygen radical removing is quickened in the oxidation of lipotropism matter, prevents reperfusion injury; Be used for the treatment of diabetes, may command blood glucose.
In the medicine optimization of C of the present invention, (Salviamitiorrhiza Bge) makes adjuvant drug with Radix Salviae Miltiorrhizae.Compendium of Material Medica record Radix Salviae Miltiorrhizae " broken stagnated blood, tissue regeneration promoting blood ".Modern pharmacological research shows that Radix Salviae Miltiorrhizae can microcirculation improvement, and anticoagulant improves the histanoxia tolerance, promotes metabolism, can also regulate immunity, strengthens capillary permeability, suppresses thrombosis.The water solublity danshensu is a kind of effective oxygen free radical scavenger.
Compatibility adjuvant Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), main effect has invigorating the spleen and replenishing QI, relaxes the property of medicine.In the side coordinating the actions of various ingredients in a prescription, relax the property of medicine, the invigorating the spleen and replenishing QI of holding concurrently can play the effect of controlling of helping for the fragrant dry strong property of Rhizoma Chuanxiong.
Optimization of C four medicines of the present invention share, and grow and oiliness, tonify without causing stagnation, cold and cold, blood circulation promoting and blood stasis dispelling and do not hinder healthy energy, and sound folding, coordination of potent and mild therapies moisten nourishing the liver and kidney, the effect that blood circulation promoting and blood stasis dispelling makes eye bright and bring into play.
Process for preparing medicine of the present invention: use Radix Rhodiolae of the present invention and make the pharmacodynamic raw materials medicine, or use Radix Rhodiolae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae and Radix Glycyrrhizae four medicines and make the pharmacodynamic raw materials medicine, all can be by usual way, be equipped with suitable adjuvant, be made into any dosage form that pharmaceutically can receive, for example water decoction, tablet, capsule, the watered pill, honeyed pill, and dosage form such as granular pattern electuary, oral liquid, wherein preferred water decoct and oral liquid.Its consumption, by contained Radix Rhodiolae crude drug equivalent wherein, the adult is equivalent to about crude drug Radix Rhodiolae 0.2～0.3g/kg by body weight medication every day, divide 2～4 times oral.
The specific embodiment
Below in conjunction with pharmacy embodiment and the checking effect of the present invention experimental example the invention will be further described.
Embodiment 1 preparation water decoction
With Radix Rhodiolae pharmacodynamic raw materials simply, or imitate raw material,, decoct with water 2～3 times through pulverizing or not adding pulverizing with Radix Rhodiolae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae and Radix Glycyrrhizae four Chinese medicine.Add 5～8 times of amounts of water at every turn, boiled 30～60 minutes.Decoct the back and collect merging filtrate promptly.When using four Chinese medicine to imitate raw material, every kind of raw material can be decocted separately, merge decoction filtrate at last, decoction also can be mixed each raw material.
Embodiment 2 preparation oral liquids
With Radix Rhodiolae pharmacodynamic raw materials simply, or imitate raw material,, decoct with water 2～3 times through pulverizing or not adding pulverizing with Radix Rhodiolae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae and Radix Glycyrrhizae four Chinese medicine.Add 5～8 times of amounts of water at every turn, boiled 30～60 minutes.Decoct the back and collect merging filtrate, with filtrate put into the vacuum concentration pan decompression (43～47 ℃ ,-0.093～0.097Mpa) is concentrated into relative density 1.23～1.27 (25 ℃); Add 95% ethanol to containing alcohol amount 70%, left standstill 72 hours, filter; Filtrate recycling ethanol is to there not being the alcohol flavor; Gained extractum adds purified water and stirs in right amount, boils 30 minutes, is cooled to room temperature, and cold preservation 48 hours filters, and regulates pH value to 7.0, accurately mends purified water to full dose, filters.Reason bottle back is canned, every bottle of 20ml.With 100 ℃ of flowing steam sterilizations 30 minutes, make oral liquid,
Experimental example 1 zoopery report
Be checking medicine of the present invention to the effect that treatment of diabetic retinopathy becomes, design and carried out zoopery, be reported as follows.
Materials and methods:
1. grouping: 40 of male Wistar rats are divided into diabetic model group-treatment group N=16 at random; Diabetic model group one not treatment group N=16; Normal control group N=8.
2. the foundation of diabetes model and administrated method: through lumbar injection streptozotocin (STZ) 60mg/kg, after 3 days, blood glucose reaches the selected diabetic model group of 16mmol/l.Simultaneously, matched group intraperitoneal injection of saline.
Medication: the treatment group gave to irritate stomach by the medicine water decoction of the present invention of embodiment 1 method preparation in modeling in 4 months, and dosage is calculated by contained Radix Rhodiolae crude drug equivalent, is the 0.3g/kg body weight, day once, and one totally month.Not treatment group and normal control group give equivalent eliminating cold for resuscitation water and irritate stomach, and same day once, one totally month.
3. eyeball is drawn materials with fixing:
1. be used for the immunohistochemistry fluorescence staining: behind the rat laparotomy, enter the thoracic cavity and cut off right ventricle, inject 4% paraformaldehyde through peristaltic pump by left ventricle, when liver becomes yellowish-brown, after getting eyeball and putting into 4% paraformaldehyde external fixation, be stored in 75% ethanol, be used for immunohistochemical staining.
2. being used for RT-polymerase chain reaction (RT-PCR) detects: after taking out rat eye, peel off complete retina and be put in and place the dry ice box to preserve in the Eppendorf pipe rapidly.
The result:
VEGF (VEGF) immunohistochemistry is measured and semi-quantitative analysis: the treatment group and not treatment organize positive expression.The treatment group is compared with not treatment group, the average gray value of treatment group obviously increases and the surface density value obviously reduces, and illustrate that the immune signal of treatment group reduces, the cell number minimizing of positive expression, promptly reduced rat retina and organized the positive expression of VEGF, statistical significance arranged between group.
In the RT-PCR modeling group, the treatment group has expression to genes of interest, and expression is lower; Not treatment group has expression to genes of interest in the modeling group, and expression is higher; The normal control group does not almost have expression to genes of interest.Show Messenger RNA (mRNA) level difference of VEGF, statistical significance is arranged between group.
Conclusion:
At present diabetic renal papillary necrosis be studies show that the infringement of patient's retinal microvascular causes a series of pathological changes such as retinal ischemia, anoxia and new vessels formation.Retinal ischemia induction of vascular growth factor release be the startup factor of retina proliferative reaction, and VEGF is the cytokine that a kind of differential stimulus vascular endothelial cell proliferation and new vessels form.There is the high affinity receptor of VEGF in the retinal blood endothelial tube, and the receptor number is many than its hetero-organization endotheliocyte.Yamagishi etc. discover that advanced glycation endoproducts (AGEs) may the microvascular balance of destroying retinal participates in the morbidity of early diabetic retinopathy by inducing pericyte's apoptosis and VEGF overexpression.Can find that in the cornea of diabetics and retina the VEGF level raises.In addition, in the non-diabetic animal, ophthalmic gives the retinal abnormalities that exogenous VEGF can cause similar diabetic renal papillary necrosis.Therefore, think that VEGF is a kind of important molecule signal of direct reflection diabetic renal papillary necrosis process.So the research and the application thereof of VEGF inhibitor and VEGF signal transduction pathway inhibitor, can in the research of diabetic renal papillary necrosis and treatment, play a positive role.
This test shows that from gene and two levels of protein expression medicine of the present invention reduces the positive expression that rat retina is organized VEGF, has shown the treatment meaning to diabetic renal papillary necrosis respectively.
Claims (5)
1. one kind is the purposes of medicine in the medicine that the preparation treatment of diabetic retinopathy becomes that pharmacodynamic raw materials is made with the Radix Rhodiolae.
2. the medicine that treatment of diabetic retinopathy becomes is characterized in that, it is to be the medicine of pharmacodynamic raw materials making with Chinese medicine Radix Rhodiolae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae and Radix Glycyrrhizae, consumption proportion is expressed as by weight, Radix Rhodiolae 10-15, Rhizoma Chuanxiong 10-15, Radix Salviae Miltiorrhizae 10-15, Radix Glycyrrhizae 10-15.
3. medicine according to claim 2 is characterized in that, each pharmacodynamic raw materials consumption proportion is expressed as by weight, Radix Rhodiolae 10, Rhizoma Chuanxiong 10, Radix Salviae Miltiorrhizae 10, Radix Glycyrrhizae 10.
4. according to claim 2 or 3 described medicines, it is characterized in that, use described pharmacodynamic raw materials, be equipped with suitable adjuvant, be made into any pharmaceutically acceptable dosage form.
5. medicine according to claim 4 is characterized in that, the pharmaceutical dosage form of made is water decoction or oral liquid.
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|---|---|---|---|
| CN2008100071887A CN101234136B (en) | 2008-02-04 | 2008-02-04 | Medicament for curing diabetes retina affection |
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|---|---|---|---|
| CN2008100071887A CN101234136B (en) | 2008-02-04 | 2008-02-04 | Medicament for curing diabetes retina affection |
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| CN101234136B true CN101234136B (en) | 2011-06-22 |
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| KR101385814B1 (en) * | 2011-12-26 | 2014-04-17 | (주)엘지하우시스 | Biodegradable resin composition and method for biodegradable sheet using the same |
| CN103893196B (en) * | 2014-04-02 | 2015-07-22 | 闫莹 | Medical application of sedoisoprosan and pharmaceutical composition of sedoisoprosan |
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