CN110721259B - Preparation method and application of compound preparation with human aldose reductase inhibitor effect - Google Patents
Preparation method and application of compound preparation with human aldose reductase inhibitor effect Download PDFInfo
- Publication number
- CN110721259B CN110721259B CN201911228738.2A CN201911228738A CN110721259B CN 110721259 B CN110721259 B CN 110721259B CN 201911228738 A CN201911228738 A CN 201911228738A CN 110721259 B CN110721259 B CN 110721259B
- Authority
- CN
- China
- Prior art keywords
- parts
- preparation
- volatile oil
- compound preparation
- extract
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/235—Foeniculum (fennel)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/22—Anacardiaceae (Sumac family), e.g. smoketree, sumac or poison oak
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/39—Convolvulaceae (Morning-glory family), e.g. bindweed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
- A61K36/738—Rosa (rose)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a preparation method and application of a compound preparation with the effect of an aldose reductase inhibitor, wherein the compound medicine is prepared from 7 medicinal materials of fennel, aloe, puncturevine caltrop fruit, rose petal, myrobalan pulp, smoked-lupulus and kadsura root by the steps of solvent extraction, volatile oil inclusion, concentration, drying, adding conventional auxiliary materials and preparing tablets, capsules, granules, pills and powder. The compound preparation has effects of refreshing brain, improving eyesight, removing stagnation and relieving pain. Through liquid-mass analysis, the main components in the formula are anthraquinone substances represented by aloin A/B and the like and polyphenol substances represented by ellagic acid and gallic acid. The barbaloin has effects of clearing away heat and toxic materials, and removing stagnation and promoting catharsis, and the polyphenols have good in vivo and in vitro antioxidant effects. Research results show that the compound preparation has in vitro antioxidant and Aldose Reductase (AR) inhibitory activity, has inhibitory activity on a polyol way induced by high sugar of human retinal pigment epithelial cells, has positive regulation effect on disease targets of diabetic eye complications, and can be used as a medicine for treating and preventing diabetic eye diseases.
Description
Technical Field
The invention belongs to the field of traditional Chinese medicines, and particularly relates to a preparation method of a compound preparation with human aldose reductase inhibitory activity and application of the compound preparation in preventing and treating diabetic retinopathy.
Background
Diabetes belongs to a metabolic disease, and is characterized mainly by long-lasting hyperglycemia due to defective insulin secretion and or impaired biological action of insulin. By 2016, more than 1 hundred million diabetics in China account for more than 10 percent of the total number of adults in China, the average prevalence rate of diabetes is slightly higher than that of diabetes in the whole world, the incidence rate of diabetes rises year by year along with population growth and the spread of unhealthy life styles such as high-sugar and high-fat diet structures and lack of sports, and the number is expected to increase to 1.5 hundred million people in 2040 years. The development of the disease process causes various metabolic disorders such as sugar, protein, fat, electrolyte and the like, and also increases the risk of suffering other serious diseases such as cardiovascular diseases and the like, thereby bringing important burden and serious influence to the health of residents and social economy.
The health threat from diabetes mainly stems from acute or chronic complications caused by hyperglycemia. About 10 years of disease, 30-40% of patients will develop at least one complication. Chronic complications of diabetes can affect a plurality of important organs of the whole body such as kidneys, eyes, feet, heart, cardiovascular and cerebrovascular vessels, peripheral nerves and the like. Among them, the influence of diabetic eye disease on the quality of life of patients is important.
The Diabetic eye disease mainly refers to Diabetic Retinopathy, Diabetic cataract, eye paralysis and the like, wherein the Diabetic Retinopathy (DR) is the most common visual complication of diabetes and is the main reason of visual impairment and blindness of adults in the working age group all over the world. According to clinical statistics of some known diabetic patients, the incidence rate of Diabetic Retinopathy (DR) in the diabetic patients is about 35%, the incidence rate rises linearly with the time of the diabetic course, and the incidence rate of Diabetic Retinopathy (DR) in the diabetic patients for more than 20 years is almost 100%. The pathogenesis of Diabetic Retinopathy (DR) has not been completely elucidated so far and no effective cure means exist, and clinical observation suggests that the pathogenesis is related to oxidative stress microvascular complications caused by hyperglycemia.
When blood sugar is normal, glucose serves to supply the body with reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH), ribose, and energy adenine nucleoside triphosphate (ATP) through the pentose phosphate pathway, and almost all glucose metabolism processes are redox reactions. The electrons provided by glucose in the reaction are mainly stored in reduced Nicotinamide Adenine Dinucleotide (NADH), and the level of reduced Nicotinamide Adenine Dinucleotide (NADH) is related to the blood glucose level. At hyperglycemia, the polyol pathway is accelerated, and the oxidative equilibrium between reduced Nicotinamide Adenine Dinucleotide (NADH) and nicotinamide adenine dinucleotide (NAD +) inclines to reduced Nicotinamide Adenine Dinucleotide (NADH), resulting in unbalanced reaction.
Because the polyol pathway consists of two different catalytic reactions, the first reaction is a reduction reaction, glucose is catalyzed by Aldose Reductase (AR) to produce sorbitol, and reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) is converted to nicotinamide adenine dinucleotide phosphate (NADP +), wherein Aldose Reductase (AR) is the main rate-limiting enzyme, and the activity is positively correlated with glucose concentration; the second reaction is catalyzed by Sorbitol Dehydrogenase (SDH), Sorbitol is acted to generate fructose, reduced Nicotinamide Adenine Dinucleotide (NADH) is converted into nicotinamide adenine dinucleotide (NAD +), Sorbitol Dehydrogenase (SDH) is insensitive to blood sugar change, and total products of polyol pathways are Sorbitol, fructose and reduced Nicotinamide Adenine Dinucleotide (NADH). In hyperglycemia, excess glucose is metabolized mainly through a polyol pathway, production of reduced Nicotinamide Adenine Dinucleotide (NADH) and sorbitol is promoted, and the level of reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) is significantly reduced. Because glutathione reductase requires reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) as a prosthetic group for reduction of oxidative glutathione (GSSG), a decrease in reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH) will further disrupt the glutathione GSH/GSSG balance, leading to further imbalanced oxidative levels, producing oxidative stress damage.
In retinal tissues, accumulation of sorbitol, a product of Aldose Reductase (AR), changes cellular osmotic pressure, resulting in cellular edema and changes in intracellular metabolism, and is considered to be one of the causes of diabetic ocular complications. Overproduction of fructose, another product of the polyol pathway, leads to protein dysfunction. The products of further fructose metabolism, 3-deoxyglucose and 3-phosphofructose, are non-enzymatic glycosylation products, excess fructose is metabolized by fructokinase, possibly bypassing the glycolysis pathway, producing excess acetyl-CoA and resulting in ATP depletion, the former leading to more protein acetylation and impaired protein function, the latter leading to cell death. The activation of the polyol pathway, resulting in fructose accumulation, may exacerbate the symptoms of diabetic complications.
In view of the important role of Aldose Reductase (AR) in the polyol pathway, inhibition of Aldose Reductase (AR) activity was found to improve diabetic symptoms by means of Aldose Reductase (AR) inhibitors and AR knockout animal models, and mature AR inhibitory drugs such as epalrestat also appeared.
At present, the market lacks a traditional Chinese medicine compound for treating diabetic complications by taking Aldose Reductase (AR) inhibition as a mechanism, and the possibility of the traditional Chinese medicine compound on the inhibitory activity of Aldose Reductase (AR) is also in the groping stage. The Chinese herbal compound has the advantages of multi-target and multi-path action mechanism and has unique advantages for preventing and controlling diabetic complications.
At present, few medicaments for preventing and treating the diabetic retinal complications are sold on the market at home. The compound preparation provided by the invention has prevention and treatment effects on hyperglycemia-induced sorbitol alternative metabolism disorder of human retinal pigment epithelial cells (ARPE-19), has similar characteristics compared with a preparation of a medicine for treating and preventing diabetic retinopathy and can be developed as a medicine for treating and preventing diabetic retinopathy.
Disclosure of Invention
The invention aims to provide a preparation method and application of a compound preparation with the effect of a human aldose reductase inhibitor, and the compound medicine is prepared from 7 medicinal materials of fennel, aloe, caltrop, rose petals, myrobalan pulp, smoked Luxiang and kadsura root, and has the effects of refreshing brain, improving eyesight, removing stagnation and relieving pain. Can be used for treating night blindness, visual deterioration, and headache. Through liquid-mass analysis, the main components in the formula are anthraquinone substances represented by aloin A/B and the like and polyphenol substances represented by ellagic acid and gallic acid. The barbaloin has effects of clearing away heat and toxic materials, and removing stagnation and promoting catharsis, and the polyphenols have good in vivo and in vitro antioxidant effects. Research results show that the compound preparation has in vitro antioxidant and Aldose Reductase (AR) inhibitory activity, has inhibitory activity on a polyol pathway induced by high sugar of human retinal pigment epithelial cells (ARPE-19), and has positive regulation effect on disease targets of diabetic eye complications.
The invention relates to a preparation method of a compound preparation with the effect of a human aldose reductase inhibitor, the compound preparation takes 500g as a base number, and is composed of 10-35 parts of aloe, 20-5 parts of rose petals, 5-20 parts of myrobalan, 10-20 parts of caltrop, 30-5 parts of fennel, 20-5 parts of smoked Luxiang and 5-10 parts of kadsura root, and is prepared by adding conventional pharmaceutical auxiliary materials, and the specific operation is carried out according to the following steps:
a. pulverizing Aloe, incense, and radix fici Pumilae respectively, and sieving the crude medicinal powder with 50-200 mesh sieve;
b. adding 6-20 times of water into rose petal, myrobalan and fructus Tribuli, extracting for 1-4 times, each time for 1-4h to obtain water extract;
c. adding 6-20 times of water into fructus Foeniculi, extracting for 1-6 hr by steam distillation to obtain extractive solution, and collecting volatile oil;
d. mixing the volatile oil with 1-10 parts of beta-cyclodextrin at 30-60 deg.C under stirring for 0.5-1 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 50-200 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solution of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating under reduced pressure at 50-70 deg.C until the relative density is 1.1, and vacuum drying at 40-70 deg.C for 24-48h to obtain extract;
f. and (d) fully mixing the extract obtained in the step (e), the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding conventional pharmaceutical excipients and preparing tablets, capsules, granules, pills or powder.
The compound preparation obtained by the method is used for preparing a medicine for treating diabetic retinopathy.
Drawings
FIG. 1 shows the effect of different concentrations of mixed extract of the compound preparation on normal growth of human retinal pigment epithelial cells (ARPE-19) in example 1 of the present invention, wherein the final concentration of the extract of the compound preparation is shown in the figure;
FIG. 2 is a graph showing the survival rate of human retinal pigment epithelial cells (ARPE-19) grown in an environment of 4.5mM and 30mM glucose after 24 hours of the compound preparation mixed extract in example 1 of the present invention, wherein the graph shows the final concentration of the compound preparation extract;
FIG. 3 shows that the compound preparation mixed extract in embodiment 1 of the present invention is applied to Na in human retinal pigment epithelial cells (ARPE-19) in an environment of 30mM glucose for 24h+-K+-schematic representation of the effect of ATPase activity, wherein the final concentration of the compound preparation extract is shown in the figure under the environment of 30mM glucose;
FIG. 4 is a schematic diagram showing the effect of 24h of the mixed extract of the compound preparation in example 1 of the present invention on sorbitol level in human retinal pigment epithelial cells (ARPE-19) under a glucose environment of 30mM, wherein the final concentration of the extract of the compound preparation under the glucose environment of 30mM is shown in the diagram.
Detailed Description
The technical solutions provided by the present invention are described in detail with reference to examples for further illustration, but they should not be construed as limiting the scope of the present invention.
Example 1
Tablets were prepared on a base of 500 g:
a. respectively pulverizing 10 parts of aloe, 20 parts of smoked Luxiang and 5 parts of boxthorn root, and sieving the crude drug powder with a 60-mesh sieve for later use;
b. adding 20 parts of rose petals, 5 parts of myrobalan and 10 parts of tribulus into 12 times of water, extracting for 2 times, extracting for 3 hours each time, and combining to obtain water extract for later use;
c. adding 30 parts of fennel into 6 times of water, extracting for 6 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 4 parts of beta-cyclodextrin at 30 deg.C, stirring for 1 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 60 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 40 deg.C under reduced pressure to relative density of 1.1, and vacuum drying at 70 deg.C for 24 hr to obtain dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crushed dry extract with the crude drug powder obtained in the step (a) and the volatile oil clathrate obtained in the step (d), adding 2 parts of conventional pharmaceutical excipients, namely lactose, 2 parts of microcrystalline cellulose, 2 parts of sodium carboxymethyl cellulose, 3 parts of sodium carboxymethyl starch and 1 part of magnesium stearate, and preparing the tablets according to a conventional pharmaceutical method.
Example 2
Tablets were prepared on a base of 500 g:
a. respectively pulverizing 25 parts of aloe, 10 parts of lavender and 5 parts of kadsura root, and sieving the crude drug powder with a 100-mesh sieve for later use;
b. 10 parts of rose petal, 15 parts of myrobalan and 15 parts of tribulus fruit are added with 10 times of water, and the mixture is extracted for 2 times, and each time is extracted for 3 hours to obtain water extract for later use;
c. adding 20 parts of fennel into 8 times of water, extracting for 5 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 5 parts of beta-cyclodextrin at 30 deg.C, stirring for 0.5 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 100 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 50 deg.C to relative density of 1.1, and vacuum drying at 70 deg.C for 24 hr to obtain dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 2 parts of microcrystalline cellulose, 2 parts of mannitol, 2 parts of sodium carboxymethylcellulose, 3 parts of crosslinked polyvinylpyrrolidone and 1 part of magnesium stearate serving as conventional pharmaceutical excipients, and preparing the tablets by a conventional pharmaceutical method.
Example 3
Tablets were prepared on a base of 500 g:
a. respectively pulverizing 10 parts of aloe, 20 parts of smoked Luxiang and 5 parts of boxthorn root, and sieving the crude drug powder with a 50-mesh sieve for later use;
b. adding 5 parts of rose petals, 10 parts of myrobalan and 20 parts of tribulus into 8 times of water, and extracting for 3 times, wherein each time is 2 hours to obtain an aqueous extract for later use;
c. adding 30 parts of cumin into 10 times of water, extracting for 4 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 6 parts of beta-cyclodextrin at 30 deg.C, stirring for 1 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 50 mesh sieve to obtain volatile oil clathrate;
e. mixing the fennel extract obtained in the step c with the rose petal, myrobalan and tribulus terrestris extract obtained in the step b, filtering, decompressing, concentrating at 70 ℃ until the relative density is 1.1, and vacuum drying at 65 ℃ for 24h to obtain dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 2 parts of conventional pharmaceutical excipients, namely lactose, 2 parts of mannitol, 2 parts of sodium carboxymethyl starch, 3 parts of cross-linked polyvinylpyrrolidone and 1 part of magnesium stearate, and preparing the tablets according to a conventional pharmaceutical method.
Example 4
Preparing capsules by taking 500g as a base number:
a. respectively crushing 15 parts of aloe, 20 parts of smoked Luxiang and 10 parts of boxthorn root, and sieving the raw medicinal powder with a 120-mesh sieve for later use;
b. adding 20 parts of rose petals, 20 parts of myrobalan and 10 parts of caltrop into 20 times of water, extracting for 1 time and 4 hours to obtain water extract for later use;
c. adding 5 parts of fennel into 12 times of water, extracting for 4 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 8 parts of beta-cyclodextrin at 40 deg.C, stirring for 0.5 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 200 mesh sieve to obtain volatile oil clathrate;
e. mixing the fennel extract obtained in the step c with the rose petal, myrobalan and tribulus terrestris extract obtained in the step b, filtering, decompressing, concentrating at the temperature of 60 ℃ until the relative density is 1.1, and vacuum-drying at the temperature of 65 ℃ for 24 hours to obtain a dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 2 parts of mannitol, 2 parts of microcrystalline cellulose, 2 parts of sodium carboxymethyl starch, 2 parts of cross-linked cellulose, 1 part of aerosil and 1 part of magnesium stearate serving as conventional pharmaceutical excipients, and preparing the mixture into capsules according to a conventional pharmaceutical method.
Example 5
Preparing capsules by taking 500g as a base number:
a. respectively pulverizing 10 parts of aloe, 10 parts of lavender and 10 parts of boxthorn root, and sieving the crude drug powder with a 200-mesh sieve for later use;
b. adding 15 parts of rose petals, 10 parts of myrobalan and 20 parts of tribulus into 6 times of water, and extracting for 4 times, wherein each time is 2 hours to obtain an aqueous extract for later use;
c. adding 25 parts of fennel into 16 times of water, extracting for 3 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 1 part of beta-cyclodextrin at 40 deg.C, stirring for 1 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 120 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 50 deg.C to relative density of 1.1, and vacuum drying at 60 deg.C for 48 hr to obtain dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 2 parts of conventional pharmaceutical auxiliary materials of starch, 2 parts of microcrystalline cellulose, 2 parts of sodium carboxymethyl starch, 2 parts of crospovidone, 1 part of aerosil and 1 part of magnesium stearate, and preparing the mixture into capsules according to a conventional pharmaceutical method.
Example 6
Granules were prepared on a base of 500 g:
a. respectively pulverizing 35 parts of aloe, 5 parts of lavender and 10 parts of boxthorn root, and sieving the crude drug powder with a 80-mesh sieve for later use;
b. adding 5 parts of rose petals, 20 parts of myrobalan and 20 parts of tribulus terrestris into 16 times of water, and extracting for 2 times, wherein each time is 4 hours to obtain a water extract for later use;
c. adding 5 parts of fennel into 20 times of water, extracting for 1 hour by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 3 parts of beta-cyclodextrin at 50 deg.C, stirring for 0.5 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 80 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 50 deg.C to relative density of 1.1, and vacuum drying at 60 deg.C for 48 hr to obtain dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 3 parts of mannitol, 3 parts of sodium carboxymethyl starch, 2 parts of microcrystalline cellulose and 2 parts of xylitol serving as conventional pharmaceutical excipients, and preparing the mixture into granules according to a conventional pharmaceutical method.
Example 7
Granules were prepared on a base of 500 g:
a. respectively pulverizing 20 parts of aloe, 5 parts of smoked Luxiang and 5 parts of boxthorn root, and sieving the crude drug powder with a 120-mesh sieve for later use;
b. adding 10 times of water into 20 parts of rose petals, 20 parts of myrobalan and 20 parts of caltrop, extracting for 3 times, and extracting for 2 hours each time to obtain water extract for later use;
c. adding 10 parts of fennel into 12 times of water, extracting for 2 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 7 parts of beta-cyclodextrin at 50 deg.C, stirring for 0.5 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 140 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 50 deg.C to relative density of 1.1, and vacuum drying at 55 deg.C for 48 hr to obtain dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 3 parts of dextrin, 3 parts of sodium carboxymethyl starch, 2 parts of microcrystalline cellulose and 2 parts of aspartame which are conventional pharmaceutical adjuvants, and preparing the mixture into granules according to a conventional pharmaceutical method.
Example 8
Pellets were prepared on a base of 500 g:
a. respectively pulverizing 35 parts of aloe, 15 parts of lavender and 5 parts of boxthorn root, and sieving the crude drug powder with a 60-mesh sieve for later use;
b. adding 5 parts of rose petals, 10 parts of myrobalan and 15 parts of tribulus into 16 times of water, extracting for 1 time and 3 hours to obtain water extract for later use;
c. adding 15 parts of fennel into 14 times of water, extracting for 3 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 9 parts of beta-cyclodextrin at 50 deg.C, stirring for 0.5 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 50 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 50 deg.C to relative density of 1.1, and vacuum drying at 55 deg.C for 24 hr to obtain extract;
f. and (d) fully mixing the extract obtained in the step (e), the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 10 parts of conventional pharmaceutical excipients of sodium carboxymethyl starch, and preparing the mixture into pills according to a conventional pharmaceutical method.
Example 9
Pellets were prepared on a base of 500 g:
a. respectively pulverizing 20 parts of aloe, 5 parts of lavender and 10 parts of kadsura root, and sieving the crude drug powder with a 140-mesh sieve for later use;
b. adding 20 parts of rose petals, 5 parts of myrobalan and 10 parts of tribulus into 8 times of water, and extracting for 4 times, wherein each time is 2 hours to obtain an aqueous extract for later use;
c. adding 30 parts of fennel into 18 times of water, extracting for 2 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 1 part of beta-cyclodextrin at 60 deg.C, stirring for 1 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 120 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 60 deg.C to relative density of 1.1, and vacuum drying at 40 deg.C for 24 hr to obtain extract;
f. and (d) fully mixing the extract obtained in the step (e), the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 10 parts of conventional pharmaceutical excipients of sodium carboxymethyl starch, and preparing the mixture into pills according to a conventional pharmaceutical method.
Example 10
Powder preparation was prepared with 500g as base:
a. respectively pulverizing 10 parts of aloe, 15 parts of smoked Luxiang and 10 parts of boxthorn root, and sieving the crude drug powder with a 50-mesh sieve for later use;
b. adding 10 times of water into 15 parts of rose petals, 15 parts of myrobalan and 15 parts of tribulus, extracting for 3 times, and extracting for 1 hour each time to obtain water extract for later use;
c. adding 20 parts of cumin into 10 times of water, extracting for 4 hours by a steam distillation method to obtain an extracting solution for later use, and collecting volatile oil;
d. mixing each part of volatile oil with 10 parts of beta-cyclodextrin at 60 deg.C, stirring for 1 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 50 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solutions of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating at 70 deg.C to relative density of 1.1, and vacuum drying at 50 deg.C for 48 hr to obtain dry extract;
f. and (d) crushing the dry extract obtained in the step (e), fully mixing the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding 5 parts of conventional pharmaceutical excipients, namely lactose and 5 parts of dextrin, and preparing the mixture into powder according to a conventional pharmaceutical method.
Example 11
The compound preparation has the in vitro antioxidant capacity:
antioxidant activity of 12, 2' -diaza-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium salt (ABTS) method:
preparation of 7mM aqueous solution of 2, 2' -diaza-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium salt (ABTS): 2, 2' -diaza-bis (3-ethylbenzothiazole-6-sulphonic acid) diammonium salt 7mM + K2S2O82.45mM and deionized water are dissolved in 5mL, mixed and dissolved thoroughly, and reacted overnight for 16h at room temperature in a dark place to form 2, 2' -dinitrogen-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium salt ABTS+Stock solution of free radical, 2, 2' -diaza-bis (3-ethylbenzothiazole-6-sulphonic acid) diammonium salt ABTS+Before use, the free radical stock solution is diluted by 95 percent ethanol until the OD value of 734nm at room temperature is 0.7 +/-0.02 which is the working concentration;
TABLE 12, 2' -diaza-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium ABTS Oxidation resistant reaction systems
Vc is used as a positive control substance, 3 groups of samples with each concentration are arranged in parallel, and after the system is fully mixed, the samples and 2, 2' -dinitrogen-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium salt ABTS+Reacting the free radical working solution for 5min in a dark place, and measuring an OD value at 734nm at the temperature of 20 ℃;
inhibition ratio (%) ([ 1- (OD)Sample (A)-ODSample pair)/(ODABTS-ODABTS zeroing)]×100%
TABLE 22, 2' -diaza-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium ABTS Oxidation resistance test results
As a result: the compound preparation obtained by the method of the invention has a fitted curve y ═ 0.6255x +3.4998 (R) for the removal rate of the antioxidant activity of 2, 2' -dinitrogen-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium salt (ABTS)20.9662), clearance IC for 2, 2' -diaza-bis (3-ethylbenzothiazole-6-sulfonic acid) diammonium salt ABTS50=67.03μg/mL;
The antioxidant activity of the 21' 1-diphenyl-2-trinitrophenylhydrazine (DPPH) method is measured as follows:
2mM 1', 1-diphenyl-2-trinitrophenylhydrazine DPPH: 1' 1-diphenyl-2-trinitrophenylhydrazine 2mM, 10mL absolute ethyl alcohol constant volume, lightproof, temperature-20 ℃ storage, DPPH before use diluted to 515nm OD value at room temperature about 0.7 as the working concentration;
TABLE 31' 1-Diphenyl-2-trinitrophenylhydrazine DPPH Oxidation resistant reaction System
Dissolving samples with 95% ethanol, setting 3 groups of samples with each concentration to be parallel, fully mixing the system, reacting the samples with 1' 1-diphenyl-2-trinitrophenylhydrazine DPPH working solution for 30min in a dark place, and measuring an OD value at 515 nm;
inhibition ratio (%) ([ 1- (OD)Sample (A)-ODSample pair)/(ODDPPH-ODDPPH zeroing)]×100%
TABLE 41' 1-Diphenyl-2-trinitrophenylhydrazine DPPH Oxidation resistance test results
As a result: the compound preparation obtained by the method of the invention has a fitting curve for the clearance rate of the antioxidant activity of 1', 1-diphenyl-2-trinitrophenylhydrazine DPPHy=0.2533x+27.821(R20.9378), clearance rate IC for 1' 1-diphenyl-2-trinitrophenylhydrazine DPPH50=42.63μg/mL。
Example 12
Compound preparation Aldose Reductase (AR) inhibitory activity in vitro:
10mM of DL-glyceraldehyde, 10mL of double distilled water with constant volume, storing at the temperature of 20 ℃ below zero, 2mM of reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH), 10mL of double distilled water with constant volume, storing at the temperature of 20 ℃ below zero, and mixing the two substances before use, wherein V is 1: 1;
TABLE 5 in vitro Aldose Reductase (AR) inhibitory Activity reaction systems and procedures
Using quercetin as positive control substance, dissolving sample and quercetin with dimethyl sulfoxide (DMSO), setting 3 groups of samples at each concentration in parallel, and measuring OD at 340 nm;
human Aldose Reductase (AR) inhibition (%) [ [1- (E)1-E0)/(S1-S0)]-[1-(D1-D0)/(S1-S0)]]/
[1-(E1-E0)/(S1-S0)]×100%
TABLE 6 in vitro inhibitory Activity of human Aldose Reductase (AR)
As a result: the compound preparation obtained by the method of the invention has a fit curve y of 2.3777x +57.042 (R) for the inhibition rate of human Aldose Reductase (AR) in vitro20.9566) and has inhibitory effect on human Aldose Reductase (AR) in vitro50=61.79μg/mL。
Example 13
The compound preparation can inhibit sorbitol bypass metabolism of human retinal pigment epithelial cells (ARPE-19):
human retinal pigment epithelial cells (ARPE-19) purchased from American Type Culture Collection (ATCC), Dulbecco's Modified Eagle Medium (DMEM)/F12 (V: V ═ 1:1, D-glucose 4.5mM, Fetal Bovine Serum (FBS) 10%, penicillin/streptomycin double antibody 1%), 5% CO2Culturing in an incubator at 37 ℃;
1. the compound preparation has the following effects on the cell viability under the influence of glucose with different concentrations:
cells 0.5-1.0X 104Inoculating the cells/well into a 96-well plate, adhering the cells to the wall overnight, replacing a drug plus culture medium (glucose is 4.5mM or 30mM), culturing for 24 hours respectively, discarding a drug-containing culture medium, adding 100 mu L/well of MTT +/FBS-/DMEM/F12 culture medium (MTT 10%), culturing for 4 hours in an incubator, discarding the MTT +/FBS-/DMEM/F12 culture medium, adding 150 mu L/well of dimethyl sulfoxide (DMSO), additionally arranging a dimethyl sulfoxide (DMSO) control well, oscillating the shaker for 10min, and measuring an OD value at 490 nm;
survival% -OD/DMSO control OD × 100% in the well dosed
The cell viability of the 100. mu.g/mL and 200. mu.g/mL treated groups was not statistically different (P >0.05) compared to the control group of cells when cultured at 4.5mM glucose content or 30mM glucose content (see FIGS. 1, 2;
2. influence of the compound preparation on the activity of ATP enzyme:
human retinal pigment epithelial cell (ARPE-19)3.5-4.0 × 105Inoculating each cell/well in 6-well plate, adhering to wall overnight, replacing 4.5mM glucose DMEM/F12 culture medium for cell control group, replacing 30mM glucose DMEM/F12 culture medium for other groups, adding compound preparation into the culture medium after 24h, respectively, the final concentration is 12.5 mug/mL and 25 mug/mL, continuing culturing for 24h, collecting cells, determining protein content, and determining protein content according to Na+-K+ATP enzyme kit Specification for Na determination+-K+-atpase concentration;
30mM glucose as compared to cell control group, model Na+-K+The ATP enzyme content was significantly reduced and the results were statistically significant (P)<0.05), 25. mu.g/mL for 24h, Na, compared to high-sugar model+-K+Significant increase in ATP-ase contentThe results are statistically significant (P)<0.05), see fig. 3;
3. the influence of the compound preparation on sorbitol bypass metabolism:
human retinal pigment epithelial cell (ARPE-19)3.5-4.0 × 105Inoculating each cell/well in a 6-well plate, adhering the cells to the wall overnight, replacing a 4.5mM glucose DMEM/F12 culture medium for a cell control group, replacing a 30mM glucose DMEM/F12 culture medium for other groups, respectively adding epalrestat EPS with the final concentration of 0.1 mu M and a 25 mu g/mL diming tablet DFR into the culture medium after 24h, respectively adding compound preparations with the final concentrations of 6.25 mu g/mL, 12.5 mu g/mL and 25 mu g/mL, continuously culturing for 24h, collecting the cells to determine the protein content, and determining the sorbitol concentration according to the specification of a sorbitol kit;
compared with a cell control group, the sorbitol level of a 30mM glucose model group is obviously increased, the result has statistical significance (P <0.05), compared with the model group, the sorbitol level of a positive control epalrestat, a patient group and each dose group of compound medicines is obviously reduced, and the result has statistical significance (P <0.05), as shown in figure 4.
Claims (2)
1. A preparation method of a compound preparation with the effect of a human aldose reductase inhibitor is characterized in that the compound preparation takes 500g as a basic number, and is composed of 10-35 parts of aloe, 5-20 parts of rose petals, 5-20 parts of myrobalan, 10-20 parts of caltrop, 5-30 parts of fennel, 5-20 parts of smoked Luxiang and 5-10 parts of kadsura root, and is prepared by adding conventional pharmaceutical auxiliary materials, and the specific operation is carried out according to the following steps:
a. pulverizing Aloe, incense, and radix fici Pumilae respectively, and sieving the crude medicinal powder with 50-200 mesh sieve;
b. adding 6-20 times of water into rose petal, myrobalan and fructus Tribuli, extracting for 1-4 times, each time for 1-4h to obtain water extract;
c. adding 6-20 times of water into fructus Foeniculi, extracting for 1-6 hr by steam distillation to obtain extractive solution, and collecting volatile oil;
d. mixing the volatile oil with 1-10 parts of beta-cyclodextrin at 30-60 deg.C under stirring for 0.5-1 hr for clathration, refrigerating at 4 deg.C for 12 hr, filtering, drying at 50 deg.C, and sieving with 50-200 mesh sieve to obtain volatile oil clathrate;
e. mixing the fructus Foeniculi extractive solution obtained in step c with the extractive solution of flos Rosae Rugosae, fructus Chebulae and fructus Tribuli obtained in step b, filtering, concentrating under reduced pressure at 50-70 deg.C until the relative density is 1.1, and vacuum drying at 40-70 deg.C for 24-48h to obtain extract;
f. and (d) fully mixing the extract obtained in the step (e), the crude drug powder obtained in the step (a) and the volatile oil inclusion compound obtained in the step (d), adding conventional pharmaceutical excipients and preparing tablets, capsules, granules, pills or powder.
2. Use of a combination preparation obtained according to the method of claim 1 for the preparation of a medicament for the treatment of diabetic retinopathy.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911228738.2A CN110721259B (en) | 2019-12-04 | 2019-12-04 | Preparation method and application of compound preparation with human aldose reductase inhibitor effect |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911228738.2A CN110721259B (en) | 2019-12-04 | 2019-12-04 | Preparation method and application of compound preparation with human aldose reductase inhibitor effect |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110721259A CN110721259A (en) | 2020-01-24 |
CN110721259B true CN110721259B (en) | 2021-12-07 |
Family
ID=69225933
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911228738.2A Active CN110721259B (en) | 2019-12-04 | 2019-12-04 | Preparation method and application of compound preparation with human aldose reductase inhibitor effect |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110721259B (en) |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105920280A (en) * | 2016-06-16 | 2016-09-07 | 中国科学院新疆理化技术研究所 | Compound preparation for treating retinopathy and amblyopia and preparation method of compound preparation |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109512870B (en) * | 2019-01-24 | 2021-04-30 | 青海大学 | Pharmaceutical composition, preparation method and application thereof |
CN110464768A (en) * | 2019-09-22 | 2019-11-19 | 徐艳群 | A kind of Chinese medicinal capsule and preparation method thereof for treating diabetic retinopathy |
-
2019
- 2019-12-04 CN CN201911228738.2A patent/CN110721259B/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105920280A (en) * | 2016-06-16 | 2016-09-07 | 中国科学院新疆理化技术研究所 | Compound preparation for treating retinopathy and amblyopia and preparation method of compound preparation |
Non-Patent Citations (1)
Title |
---|
糖尿病视网膜病变发病机制及其药物治疗研究的进展;张健;《心血管康复医学杂志》;20160630;第25卷(第3期);第339-341页 * |
Also Published As
Publication number | Publication date |
---|---|
CN110721259A (en) | 2020-01-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Ouassou et al. | Inhibition of α-glucosidase, intestinal glucose absorption, and antidiabetic properties by Caralluma europaea | |
JP7010506B2 (en) | A method for producing a Jiaogulan leaf extract that increases the content of low-molecular-weight effective saponin and reduces the content of benzopyrene, and the Jiaogulan leaf extract obtained thereby. | |
JP6126107B2 (en) | SIRT-1 activator containing syringaresinol | |
CN102885937B (en) | The preparation method of Calyx seu fructus physalis effective part group and application thereof | |
CN109078011A (en) | The application of iris aglycone and its derivative in prevention and treatment insulin resistance disease medicament | |
CN110721259B (en) | Preparation method and application of compound preparation with human aldose reductase inhibitor effect | |
Das et al. | Effects of crystal derived from Stevia rebaudiana leaves on Alloxan induced type-1 diabetic mice | |
CN104857040A (en) | New purpose of embelia parviflora wall for preparing medicines for treating liver fibrosis | |
KR101050003B1 (en) | Composition for inhibiting obesity, containing the extract as an active ingredient | |
WO2017121333A1 (en) | Use of cistanche tubulosa extract and isoacteoside in protection of muscles | |
CN103599340A (en) | Pharmaceutical composition used for treating and preventing diabetes and eye complications thereof, and applications of the pharmaceutical composition | |
CN110772596B (en) | Compound Chinese medicine peach blossom extract and its preparation process and use as medicine for treating diabetic cardiomyopathy | |
KR100523441B1 (en) | Active extracts from natural plants having anti-obesity and anti-diabetes | |
KR101385191B1 (en) | Use of Cichorium intybus extracts for preventing, treating improving muscular atrophy | |
CN112870290A (en) | Freckle-removing and depression-resolving composition and preparation method thereof | |
CN112716988A (en) | Application of extract of cissampelos dunculata in preparation of medicine for preventing and/or treating diabetic nephropathy | |
CN101843669B (en) | Chinese medicinal effective-part composition for treating coronary heart diseases | |
CN110693928B (en) | Use of apocynum venetum leaf polyphenol | |
Sudipta et al. | Evaluation of antidiabetic activity and histological study of Cyperus kyllinga Endl. roots | |
KR20030059951A (en) | Composition containing an extract of sopungsungi-won crude drug complex for preventing and treating diabetes mellitus | |
CN112716937B (en) | Active ingredient composition with synergistic blood sugar reducing function and preparation method thereof | |
JP3968179B2 (en) | Treatment for diabetic peripheral nerve injury | |
CN114736182B (en) | Compound for resisting myocardial ischemia reperfusion injury, dai medicine composition and application thereof | |
Ozougwu et al. | Methanol leaf extract of Desmodium velutinum (Wild.) DC and acarbose exhibit additive pharmacological effects in diabetic Wistar rats | |
Aulia et al. | Influence of Cinnamon Extract (Cinnamomum burmanii) Provision on the Reduction of Blood Glucose Level of Hyperglycemic Male Wistar Rats |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |