CN116139211A - Traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application thereof - Google Patents
Traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application thereof Download PDFInfo
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- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
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Abstract
The invention discloses a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application thereof. The traditional Chinese medicine composition comprises the following raw materials of astragalus, cassia twig, medlar, pipewort and raw pollen typhae. The traditional Chinese medicine composition has no obvious adverse reaction, is safe and reliable, has good medication safety, has strict formula, has the effects of tonifying qi, warming yang, promoting blood circulation and removing obstruction in collaterals by selecting the formula components and controlling the addition amount of the formula components, effectively treats non-proliferative diabetic retinopathy, has curative effects on delaying retinopathy, eyeground microangioma and eyeground hemorrhage, is a multicenter clinical study established in central random, double-blind and placebo control, and has high-quality circulation evidence as a support.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicines. More particularly relates to a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application thereof.
Background
According to the latest report of the international diabetes consortium (IDF), about 4.63 million adults aged 20-79 worldwide had Diabetes Mellitus (DM), and it was expected that the DM patient would reach 5.784 million in 2030. Among them, retinopathy (DR) is one of the important microvascular complications of DM, which is the main causative cause of blindness. Clinically, early prevention of DR is mainly fundus screening, and risk factors such as blood sugar, blood pressure and blood fat need to be well controlled in the whole process, and at present calcium oxybenzene sulfonate, anti-Vascular Endothelial Growth Factor (VEGF), glucocorticoid and laser surgery treatment are still the first choice therapeutic measures, but the wide application of the medical composition is limited due to poor curative effect and side effect. The compound red sage dripping pill, astragalus granule, compound thrombus eliminating capsule and other Chinese medicine with multiple targets may be used as effective substitution for DR.
At present, high-quality evidence-based evidence indicates that the traditional Chinese medicines comprise compound red sage root dripping pills, astragalus and Ming granules and compound thrombus-relieving capsules, and have remarkable treatment effect on DR. Wherein, the compound red sage root dripping pills and astragalus root-Ming granules are recommended in the Chinese type 2 diabetes prevention and cure guide 2017 edition. The research shows that the compound red sage dripping pill has obviously better comprehensive curative effect than that of the control group in the clinical treatment of non-proliferation period DR (NPDR), can improve vision, reduce hemangioma number and hemorrhagic area, has better curative effect on DR and has higher safety. A random, double-blind and placebo-controlled clinical study shows that after 24 weeks of intervention of NPDR patients, the effective rate and the effective percentage of fundus fluoroscopic examination of the high-dose compound red-rooted salvia drop pill group and the medium-dose compound red-rooted salvia drop pill group are respectively 74% and 77%, which are obviously higher than that of the control group by 28%. For ophthalmoscopy, the high-dose and medium-dose compound red sage root dripping pill groups showed 42% and 59% respectively, which are significantly higher than 11% of placebo group, and no clinically significant adverse events were observed. The QIMING granule can be used as Chinese medicinal compound for relieving retinal hypoxia and ischemia by increasing retinal blood flow and improving blood circulation of DR patient. The traditional Chinese medicine syndrome display efficiency of 107 cases of astragalus granule traditional Chinese medicine groups after 3 months treatment is obvious by adopting a double-blind double-simulation, random, comparison and multi-center clinical test research method, and the research shows that the astragalus granule is safe and effective in treating NPDR. The compound thrombi dredging capsule is also an effective drug for treating DR, and 19 RCTs are included in one Meta analysis, and 1778 patients are involved. The clinical total effective rate, vision, visual field gray value, macula thickness, hemangioma volume, hemangioma number and bleeding spot area of the test group are all significantly better than those of the control group (P < 0.001), and no obvious adverse reaction is seen in the patients of the group 2. The results show that the compound thrombus-removing capsule and the calcium dobesilate tablet have better curative effect than the calcium dobesilate tablet alone for treating early DR. The compound thrombus treating and photocoagulation treatment has better curative effects than photocoagulation and conventional research groups in vision change, fundus change, macular edema fading and other aspects. However, the problem of the traditional Chinese medicine of delaying the DR progress cannot be solved at present.
Therefore, it is very important to develop a traditional Chinese medicine composition for effectively treating non-proliferative diabetic retinopathy.
Disclosure of Invention
The first aim of the invention is to provide a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy.
The second aim of the invention is to provide an application of the traditional Chinese medicine composition in preparing medicines for treating non-proliferative diabetic retinopathy.
In order to achieve the first object, the present invention adopts the following technical scheme:
the invention provides a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, which comprises the following raw material medicines of astragalus, cassia twig, medlar, pipewort and raw pollen typhae.
The invention effectively treats non-proliferative diabetic retinopathy by selecting the components of the formula and controlling the addition of the components of the formula, and the medicines cooperate and cooperate, improves microcirculation, promotes the acceleration of microcirculation blood flow speed of the generated obstacle, improves the tolerance of the organism to hypoxia, improves the ischemia state and improves the rheological property of blood, and integrally accords with the treatment principle of Chinese medicine for invigorating qi, warming yang, activating blood and dredging collaterals. The traditional Chinese medicine composition has more simplified formula, and the multi-center clinical study of central randomness, double blindness and placebo control shows that the traditional Chinese medicine composition has definite curative effect, can effectively delay the increase of retinopathy and eyeground microangioma, has the declining trend of eyeground bleeding rate, has high-quality circulation evidence as a support, and has stronger popularization significance.
Further, the formula of each raw material is as follows: 3 to 120 parts of astragalus, 3 to 30 parts of cassia twig, 3 to 70 parts of medlar, 3 to 30 parts of pipewort and 3 to 30 parts of raw pollen typhae.
Further, the formula of each raw material is as follows: 3 to 60 parts of astragalus, 3 to 15 parts of cassia twig, 3 to 30 parts of medlar, 3 to 15 parts of pipewort, and 3 to 15 parts of raw pollen typhae.
Within the range of the proportion, the traditional Chinese medicine composition can achieve the aim of treating non-proliferative diabetic retinopathy. For convenient blending and use, the inventor further prefers the following raw material medicine proportioning modes, and the curative effects of the raw material medicines are determined:
(1) 30g of astragalus, 9g of cassia twig, 9g of medlar, 9g of pipewort and 9g of raw pollen typhae;
(2) 15g of astragalus, 6g of cassia twig, 9g of medlar, 9g of pipewort and 9g of raw pollen typhae.
The traditional Chinese medicine composition provided by the invention has a strict formula, is complete in monarch, minister, assistant and guide, and has the following formula solutions: astragalus root is sweet in nature and slightly warm in nature, enters lung and spleen meridians, is a monarch drug, is thin in smell and thick in taste, has the effects of tonifying qi and raising yang, nourishing blood and promoting production of body fluid, tonifying defensive and strengthening exterior, and can accelerate blood flow speed and improve blood supply quality; fructus Lycii is sweet in taste, and is used as ministerial drug for nourishing liver, invigorating kidney, nourishing yin, improving eyesight, and replenishing essence, and both can be used for treating diabetes. The local condition of retinopathy is the core pathogenesis of the blood stasis in collaterals. Ramulus Cinnamomi is also ministerial drug, and has effects of dredging collaterals, pungent and sweet, warming, promoting qi to warm, warming blood, warming and resolving cold stagnation, warming yang, invigorating spleen, invigorating qi, and improving blood supply, and can accelerate blood flow and improve blood supply quality; the raw pollen typhae is an adjuvant drug, has sweet taste and flat nature, is smooth in nature, can stop bleeding and remove stasis, has the effects of promoting blood circulation and removing stasis, can stop bleeding without retaining stasis, can be applied to bleeding symptoms, no matter cold and heat, and has stasis, and is a good product for stopping bleeding and removing stasis. Flos Eriocauli, with pungent and warm nature, is an adjuvant drug, and can treat various diseases in the eyes by activating stomach Shu Yang and developing shaoyang and Yang Mingqing qi, and then is a target drug for improving eyesight and removing nebula. All the medicines are used together to play the roles of tonifying qi, warming yang, promoting blood circulation and removing obstruction in collaterals.
In use, the traditional Chinese medicine composition can be decocted with water according to the traditional usage of the prescription, taken as soup, or refined with water or other proper solvents, and made into various solid preparations such as tablets, granules, capsules and the like according to the conventional preparation process.
To enable the formulation of the present invention, pharmaceutically acceptable excipients are added in the preparation of the formulation, for example: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, matrices, and the like. The filler comprises: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, and the like; the disintegrating agent comprises: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, crosslinked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, crosslinked sodium carboxymethyl cellulose, and the like; the lubricant comprises: magnesium stearate, sodium lauryl sulfate, talc, silica, and the like; the suspending agent comprises: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, and the like; the adhesive comprises: starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose, and the like; the sweetener comprises: saccharin sodium, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid, etc.; the flavoring agent comprises: sweetener and various flavors; the preservative comprises: nipagin, benzoic acid, sodium benzoate, sorbic acid and salts thereof, benzalkonium bromide, chlorhexidine acetate, eucalyptus oil and the like; the matrix comprises: PEG6000, PEG4000, insect wax, and the like.
In order to achieve the second purpose, the invention provides application of the traditional Chinese medicine composition in preparing medicines for treating non-proliferative diabetic retinopathy.
The beneficial effects of the invention are as follows:
the invention discloses a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application thereof. The traditional Chinese medicine composition comprises the following raw materials of astragalus, cassia twig, medlar, pipewort and raw pollen typhae. The traditional Chinese medicine composition has no obvious adverse reaction, is safe and reliable, has good medication safety, has strict formula, has the effects of tonifying qi, warming yang, promoting blood circulation and removing obstruction in collaterals by selecting the formula components and controlling the addition amount of the formula components, effectively treats non-proliferative diabetic retinopathy, has curative effects on delaying retinopathy, eyeground microangioma and eyeground hemorrhage, is a multicenter clinical study established in central random, double-blind and placebo control, and has high-quality circulation evidence as a support.
Detailed Description
In order to more clearly illustrate the present invention, the present invention will be further described with reference to preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and that this invention is not limited to the details given herein.
Example 1
Basic prescription: 30g of astragalus, 9g of cassia twig, 9g of medlar, 9g of pipewort and 9g of raw pollen typhae.
The preparation method comprises the steps of grabbing the raw materials according to the prescription, adding water for decoction for 2 times, each time for 1h, filtering, and combining the decoctions.
Example 2
Basic prescription: 15g of astragalus, 6g of cassia twig, 9g of medlar, 9g of pipewort and 9g of raw pollen typhae.
The preparation method comprises the steps of grabbing the raw materials according to the prescription, adding water for decoction for 2 times, each time for 1h, filtering, and combining the decoctions.
Clinical trials
1 subject of study
1.1 general data
On the basis of uniform administration of calcium dobesilate (guide's light, 500mg, 3 times daily, produced by ebwe Pharma gas.m. b.h nfg.kg), subjects meeting the criteria for enrollment were randomized into 2 groups using a central randomized, double-blind, placebo parallel-controlled, multi-center clinical study design method, study group was administered the formulation of example 2 (1 dose/day, 2 times divided), control group was administered placebo (1 dose/day, 2 times divided), and treatment course was 48 weeks. The study was conducted on 112 patients, 57 study groups, and 55 control groups.
1.2 inclusion criteria
(1) The disease degree is a non-proliferation period according with DR diagnosis; (2) age 30-70 years; (3) and signing an informed consent form.
1.3 exclusion criteria
(1) Patients after retinal photocoagulation, patients suitable for photocoagulation treatment, patients with PDR at one or both eyes, patients with DR caused by T1DM, and patients with other ocular diseases (such as glaucoma, cataract, NPDR, uveitis, retinal detachment, optic nerve disease, and ocular fundus lesions with high myopia, etc.) with obvious ocular fundus examination.
(2) Is combined with serious primary diseases such as cardiovascular, liver, kidney and hematopoietic system, wherein serum transaminase is greater than 2 times of normal value, serum creatinine is greater than upper limit of normal value, and is suitable for mental patients.
(3) Pregnant, women in preparation for pregnancy or lactation, or those with a history of drug allergy.
(4) Other drug clinical researchers were enrolled in the last month.
(5) Drugs other than calcium dobesilate for DR were used in nearly 1 week.
(6) Systolic pressure greater than 160mmHg or diastolic pressure greater than 100mmHg.
(7) DM ketosis, ketoacidosis and severe infections occur within nearly 1 month.
(8) Alcoholism and/or psychoactive substances, substance abusers and dependents during the last 5 years.
(9) According to the judgment of researchers, other lesions or conditions which reduce the possibility of entering groups or complicate the entering groups, such as the conditions of frequent change of working environment, unstable living environment and the like, which are easy to cause visit.
1.4 stop and exit criteria
Investigator-decided exit
Subject withdrawal refers to the decision by the researcher that the case withdrawn from the study in the event that the enrolled subject had an unfavorable course of the study.
(1) In the study, the fundus lesion is progressed to the proliferation stage or subjected to laser photocoagulation, namely the end point index of the study is reached, the patient is withdrawn from the study, and the curative effect is judged as invalid, so that the fundus lesion is a complete case.
(2) In the study, the vision of the DR patient is reduced by 3 lines or more than 3 lines, the patient is withdrawn from the study, the curative effect is judged to be invalid, and the treatment can be changed into other methods.
(3) In the study, the subjects had developed certain complications, complications or specific physiological changes, which were not suitable for continued study.
(4) In the study, subject compliance was poor, and the drug used was less than 80% or more than 120% of the prescribed amount.
(5) In the study, cases of blindness breaking or emergency blindness uncovering were performed.
(6) In the study, a forbidden drug prescribed by the protocol was used.
Subjects self-exited the study
Subject is entitled to withdraw from study halfway or subject is not explicitly proposed to withdraw from study, but is no longer subject to drug administration and detection and is not interviewed, also referred to as "withdraw" (or "abscission") according to the rules of informed consent. The reason for its exit should be known as much as possible and recorded. Such as: the subjective curative effect is poor; are difficult to tolerate for certain adverse reactions; something can not continue to accept clinical studies; economic factors; or missing a visit for reasons not described, etc. For any reason, the case record table of the case which is withdrawn from the study should be kept, and the last detection result is converted into a final result, so that the full data set analysis of the curative effect and the adverse reaction is carried out.
1.5 reject case criteria
(1) After the group, the subjects were found to be non-inclusion-standard or exclusion-standard cases.
(2) The forbidden drugs specified by the scheme are used, and are rejected due to the violation of the clinical test scheme.
(3) Cases that have not been taken after inclusion should be rejected.
(4) There were no cases that could be assessed for recording after dosing.
Whether to reject or not, and determining on a blind state examination meeting at the end of the study.
1.6 observing and treating the efficacy index
Main evaluation index
Fundus retinal microvascular lesion extent (graded according to DR severity scale) varies. According to the change of the degree of the fundus retinal microvascular lesion (no, mild non-proliferation stage, moderate non-proliferation stage, severe non-proliferation stage and proliferation stage), the aggravation means that the degree of the fundus retinal microvascular lesion is heavier by more than 1 grade than that before treatment, namely the mild non-proliferation stage becomes moderate and more, the moderate non-proliferation stage becomes severe and more, and the severe non-proliferation stage becomes proliferation stage.
Secondary evaluation index
The changes of the eyeground retinal microangiopathy microangioma and the bleeding amount of the patient before and after the administration are compared.
Therapeutic efficacy observation index
Color fundus photography (every 6 months): the fundus change index (retinal microangiopathy) is mainly evaluated in the maximum range observed by mydriasis retrospective ophthalmoscopy, and is comprehensively determined by combining a color fundus photograph or fundus fluorescence angiography. Fundus fluorescence angiography (every 6 months): the fundus fluorescence angiography is adopted to display, and the fundus fluorescence angiography examination requires more than 10 minutes to observe. Vision was corrected (every 4 weeks).
Observability index
(1) Background data observation (0 week)
a demographics: gender, age, height, weight, etc.
b general clinical data: medical history, course of disease, treatment history, combined diseases, medication, etc.
(2) Diagnostic and monitoring indicators
a blood pressure and GLU detection. (every 4 weeks)
And detecting bHbAlc and blood fat. (every 3 months)
c. Ophthalmic routine examination and fundus examination, including intraocular pressure, anterior ocular segment, lens, vitreous body; crystals, glass bodies describe cloudiness. (every 6 months)
1.7 basal therapy
(1) DM education.
(2) DM diet.
(3) And the blood sugar is reasonably controlled.
(4) Calcium dobesilate (1 granule/time, 3 times/day) was taken.
1.8 safety index
The following monitoring criteria were used to evaluate security:
(1) vital signs: such as body temperature, blood pressure, respiration, heart rate, etc. (every 4 weeks)
(2) Blood, urine and stool are common. (every 3 months)
(3) Electrocardiography, five items of liver functions include glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), glutamyl transferase (GGT), serum alkaline phosphatase (ALP), total Bilirubin (TBIL), and renal functions include Blood Urea Nitrogen (BUN), creatinine (Cr). (every 3 months)
(4) Adverse events (detailed record over time) were required in detail as follows:
according to preclinical study data, patients' adverse events need to be observed in clinical studies, although there are no specific adverse reactions. The adverse event record table is filled in faithfully, and the occurrence time, severity, duration, effective measures and the return of the adverse event are recorded.
The judgment standard of the severity of the adverse event is light: mild discomfort, the subject can tolerate no impact on treatment, no special treatment is needed, and no impact on rehabilitation of the subject. In (a): moderate discomfort, intolerable to the subject, special handling, and direct impact on the recovery of the subject. Weight: severe discomfort, life threatening, fatal or disabling of the subject, requires immediate emergency treatment.
Judging the causal relationship between adverse events and medicines:
(1) causal judgment index for judging adverse event
and a, the time for starting the administration and the suspicious adverse reaction have no reasonable sequence.
b whether the suspected adverse reaction corresponds to the known type of adverse reaction of the drug.
c the suspected adverse reactions can be explained by the effects of concomitant medication, the clinical condition of the patient or the effects of other therapies.
d, after stopping the medicine or reducing the quantity, whether the suspicious adverse reaction disappears or is reduced.
e, after re-contacting the suspected medicine, whether the same reaction reappears.
Causal decision criteria: and sequentially judging according to the 5 judgment indexes.
(2) Causal judgment of adverse event
TABLE 1 adverse event cause and effect judgment comparison Table
Description: +affirmative, -negative, ±difficult to affirmative or negative,? The situation is unknown.
According to the table above, the following relationship between the adverse event of class 5 and the drug is determined: 1-affirmative correlation, 2-possible correlation, 3-indeterminate, 4-possible correlation, 5-affirmative correlation. The total number of cases of 1+2+3 is used as a numerator for the calculation of the occurrence rate of adverse reaction, and all selected cases for the evaluation of adverse reaction are used as denominators.
Treatment of adverse events: the reporting method comprises the following steps: any adverse events, such as subjective discomfort of patients and laboratory detection abnormality, need to be carefully treated, carefully analyzed and immediately taken measures to protect the safety of the subjects. The processing procedure is as follows: details are recorded in a Case Record Form (CRF) table, and repeated for 24 hours, 7 days, and 14 days according to circumstances. Record its duration, return, disappearance, etc.
Definition and treatment of serious adverse events: serious adverse events (Severe Adverse Event, SAE): refers to the unpredictable following clinical events occurring at any dose: hospitalization, prolonged hospitalization time, disability, impaired working ability, life-threatening or death, and congenital malformation. And (3) treatment:
any SAE that occurs during the course of the test must be reported immediately to the current or major research unit medical ethics committee, the sponsor, and the "SAE report form" must be filled in to the national food and drug administration within 24 hours. Notifying the CRF list of the telephone and the contact.
The treatment measures are as follows: when the patient is in emergency, the main researchers of the research unit can read the emergency letters of corresponding numbers taken by the patient (but two witness persons are needed to be present and corresponding records are needed to be made), and the treatment results are correspondingly treated according to the medicines and the symptoms, so that the clinical inspectors are informed of the treatment results, and the researchers should record the blind breaking reason, date, treatment condition, result and signature in detail on the case report table.
Follow-up untapped adverse events: all adverse events should be tracked until properly resolved or the condition is stable. The present study defines pregnancy as SAE: women who have a potential to develop without taking appropriate contraceptive measures cannot enter the study.
1.9 statistical method
General principle
All statistical tests were run on both sides, and a P value of less than or equal to 0.05 would be considered statistically significant for the differences tested. The quantitative index description will calculate the number of examples, the average, the standard deviation, the median, the minimum and the maximum. The classification index is described by various cases and percentages.
Statistical analysis method
(1) Entry and completion conditions
The cases of entering and exiting the group, the cases of completing the group and the reasons of falling off are listed, and the cases of entering the group, the safety and the effectiveness analysis data set are described.
(2) Baseline equalization analysis
Baseline was defined as 0 days (subjects into the group). The equalization analysis of the base values is directed to basic demographic characteristics, vital signs, efficacy related indicators, etc. of cases into groups to illustrate whether the two groups of base conditions are comparable. Wherein, quantitative indexes (such as age, course of disease, GLU, hbAlc and the like of two groups) list examples, average, standard deviation, median, maximum and minimum values, and are compared by adopting t test/Wilcoxon rank sum test; qualitative index (such as sex, ethnicity, marital status, heart rhythm, past history, family history, allergy history, past treatment of this disease, degree of illness, etc.), χ is used 2 The test/exact probability method is compared.
(3) Impact test evaluation factor comparison:
a combined administration condition analysis
The numbers and percentages are listed and compared using chi-square test/Fisher exact probability method.
b analysis of medication compliance
The number and percentage of cases with the drug dosage of < 80% or > 120% and 80% -120% are listed, and are compared by using a chi-square test/Fisher exact probability method.
c time of administration
Time of administration = last time of administration-time of first time of administration +1 (day). The examples, mean, standard deviation, median, minimum, maximum were calculated and compared using t-test/Wilcoxon rank sum test.
(4) Validity analysis
The main curative effect index is as follows: by using χ 2 And (5) testing, and comparing the exacerbation rate of the degree of the retinal microvasculopathy of the two groups of eyebases.
Secondary efficacy index: changes in microangioma number, bleeding number from baseline after treatment were described, and examples, mean, standard deviation, median, minimum, maximum were calculated, and intra-group comparisons were performed using paired t-test/symbol rank test, and inter-group comparisons were performed on changes from baseline after two groups of treatments using t-test/Wilcoxon rank sum test.
Monitoring indexes: post-treatment metrics and changes from baseline are described, examples, mean, standard deviation, median, minimum, maximum are calculated, intra-group comparisons are made using paired t-test/symbol rank test, and inter-group comparisons are made for changes from baseline after two groups of treatments using t-test/Wilcoxon rank and test.
(5) Security analysis
a safety-related laboratory checks
All completed test items are listed for laboratory tests in the form of a cross table (judged according to clinical significance) before and after treatment, and test items showing abnormalities after treatment are listed.
b adverse events
The types, severity, relationship to trial drugs, etc. of all adverse events during the study will be tabulated.
c vital signs
Changes before and after treatment of signs (body temperature, heart rate, respiration, blood pressure) are described, and examples, mean, standard deviation, median, minimum, maximum are calculated and compared using t-test.
(6) Statistical analysis software
Statistical analysis was performed using SAS9.3 software. The statistical analysis of the subject is completed by a third party statistical staff, and a detailed statistical analysis plan is individually and in detail formulated by the statistical analysis staff before the study is started and is determined after the study is conducted with the subject group leader.
1.10 research ethics requirements
The clinical study will follow the declaration of helsinki (2010 edition) and the relevant clinical study specifications and regulations of china. The study was conducted after approval by the ethics committee of the subject responsible entity prior to the study initiation. Before each patient enters the study, the researcher is responsible for introducing the purposes, procedures and possible risks of the study, either in written form, to or in a designation representative of the integrity and completeness of the study. The patient should be made aware that they have the right to exit at any time. An informed consent must be given to each patient prior to enrollment. The researcher is responsible for ensuring that each patient signs an informed consent before entering the study and remains in the study archive. For a patient with a potential pregnancy, the patient must be informed that the pregnancy is likely during the study, the study may be at risk to the fetus, the patient must agree that contraceptive measures must be taken in the study to participate in the study, and if the patient is suspected of not being able to enter the study.
2 results of the study
2.1 incorporation of patient completion and withdrawal conditions
The patient procedure was included, 112 cases were screened, 0 cases were screened failed, 112 cases were screened successfully, 57 cases were study group-in, and 55 cases were control group-in. The total analysis set included 112 (study group 57, control group 55) and 97 (study group 47, control group 50) in compliance with the protocol set. Of these, study group, 44 completed study, 13 withdrawn study (4 cases were considered poor in efficacy, subject required withdrawal; 8 cases were considered poor in subject compliance, 1 case was considered withdrawal by the investigator for other reasons), control group, 47 completed study, 8 withdrawn study (3 cases were considered poor in efficacy, subject required withdrawal; 4 cases were considered poor in subject compliance, 1 case was considered withdrawal by the investigator for other reasons), and no deviation of the protocol was observed, and the results are shown in table 2.
Table 2 inclusion of patients into groups and completion of study
Note that: the percentages are calculated by taking the number of each group of random access examples as a denominator.
2.2 inclusion of patient baseline characteristics
Patients included in both groups had an age median of 58.00 years, 59 men (52.7%), and a BMI median of 25.02kg/m 2 The median of DM disease course is 10.00 years, the median of NPDR disease course is 1.00 years, other DM complications mainly comprise peripheral neuropathy (42.0%), peripheral vasculopathy (20.5%), other combined diseases mainly comprise hypertension (27.7%), hyperlipidemia (12.5%), and main combined administration mainly comprise metformin (64.3%), insulin (64.3%). In the NPDR lesion degree, the target eye has a moderate non-proliferation period of 27.7%, a moderate non-proliferation period of 66.1% and a severe non-proliferation period of 6.3%; the proportion of the eyes in the medium and slight non-proliferation period is 26.8 percent, the proportion of the eyes in the medium and non-proliferation period is 61.2 percent, and the proportion of the eyes in the severe non-proliferation period is 5.4 percent. The median of vision correction for both the target eye and both eyes is 0.80, and the median of intraocular pressure for both the target eye and both eyes is 15.00. The median of systolic pressure (SBP) was 130.00mmHg, the median of diastolic pressure (DBP) was 80.00mmHg, the median of HbAlc was 7.75%, the median of GLU was 8.11mmol/L, the median of TC was 4.78mmol/L, the median of TG was 1.34mmol/L, the median of HDL was 1.28mmol/L, and the median of LDL was 2.82mmol/L. There was no significant difference in both baseline characteristics, indicating that both baseline levels were consistent, and the statistics are presented in table 3.
Table 3 inclusion study group baseline characteristics
2.3 evaluation of Main efficacy
Retinopathy exacerbation rate
For the target eyes, the exacerbation rate of the study group was 7.0% (4/57), the exacerbation rate of the control group was 14.5% (8/55) and the two groups were not different (p=0.198) at 24 weeks of administration; at week 48, the study group had an exacerbation rate of 7.0% (4/57), the control group had an exacerbation rate of 14.5% (8/55), and the two groups were not different (p=0.198). For both eyes, at 24 weeks of administration, the exacerbation rate of the study group was 9.6% (11/114), the exacerbation rate of the control group was 17.3% (19/110), and there was no difference between the two groups (p=0.094); at week 48, the study group had an exacerbation rate of 8.8% (10/114), the control group had an exacerbation rate of 11.8% (13/110), and the two groups were not different (p=0.453). The results indicate that the aggravation rate of the study group is lower than that of the control group, and the aggravation rate of the study group is lower than that of the control group, so that the traditional Chinese medicine composition has the trend of reducing the aggravation rate of NPDR.
2.4 evaluation of Secondary efficacy
The eyeground microangioma quantity of two groups of patients before and after taking medicine
For the target eyes, the relative baseline change of the study group administration 24 weeks was-1.1±5.53 (n=49, p=0.178), the relative baseline change of the control group administration 24 weeks was-3.8±20.52 (n=38, p=0.259), and no obvious difference was found between the two groups (p=0.242); study group showed a change of-4.5±14.43 (n=49), significant difference (p=0.035), control group showed a change of 3.8±19.29 (n=38, p=0.243), and no significant difference (p=0.072). For both eyes, the relative baseline change for study group administration was-0.7±8.46 (n=98, p=0.432), the relative baseline change for control group administration was-1.9±24.28 (n=76, p=0.489), and there was no significant difference between the two groups (p=0.062); study group showed a relative baseline change of-2.7±14.23 (n=98, p=0.059) for 48 weeks, control group showed a relative baseline change of 4.7±18.18 (n=76, p=0.028), and the difference between the two groups was significant (p=0.011). The results suggest that the traditional Chinese medicine composition has the tendency of reducing the number of NPDR microangioma.
Fundus hemorrhage change of two groups of patients before and after administration
For the target eye, the study group had a relative baseline change of 1.7±21.12 (n=32, p=0.648) for 24 weeks, and the control group had a relative baseline change of 1.0±9.43 (n=25, p=0.615), with no significant difference between the two groups (p=0.759); study group treatment was given a relative baseline change of-0.9± 19.77 (n=30, p=0.805) for 48 weeks, control group treatment was given a relative baseline change of 2.0±6.29 (n=25, p=0.125) for 48 weeks, and there was no significant difference between the two groups (p=0.338). For both eyes, the study group had a relative baseline change of-0.2±17.43 (n=65, p=0.910), the control group had a relative baseline change of 0.1±8.36 (n=50, p=0.960), and there was no significant difference between the two groups (p=0.881); study group had a relative baseline change of-2.4±17.11 (n=61, p=0.279) for 48 weeks, control group had a relative baseline change of 1.6±5.09 (n=50, p=0.029) for 48 weeks, and the difference between the two groups was significant (p=0.004), suggesting that the traditional Chinese medicine composition had a tendency to reduce the number of NPDR fundus hemorrhage.
2.5 Security analysis
Compliance of two groups of patients to take medicine
Table 4 shows that the compliance of two groups of patients is 80% -120%, and the results show that the compliance of two groups of calcium paraoxybenzene sulfonate and the traditional Chinese medicine composition of the application is good, and the two groups have no difference.
Table 4 compliance with dosing
Two-group patient safety
Table 5 shows two groups of adverse event descriptions, showing that during treatment, 2 adverse events occurred in total for both groups, with 1 adverse event occurring in the study group, drug-related, patient withdrawal from the study; wherein the control group showed 1 adverse event, related to drug, and the patients were withdrawn from the study.
Table 5 two sets of adverse event descriptions
And (3) injection: [1] adverse events associated with study drug: the correlation with study drug was judged as: adverse events that are "positively related", "likely related", "undetermined". The lack of relationship determination is classified as the associated TEAE. [2] TEAE resulting in withdrawal of the subject: whether the patient has therefore exited the study as a result of an adverse event, yes is selected.
It should be understood that the foregoing examples of the present invention are provided merely for clearly illustrating the present invention and are not intended to limit the embodiments of the present invention, and that various other changes and modifications may be made therein by one skilled in the art without departing from the spirit and scope of the present invention as defined by the appended claims.
Claims (7)
1. A traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy is characterized in that the traditional Chinese medicine composition comprises raw materials including astragalus mongholicus, cassia twig, wolfberry fruit, pipewort and raw pollen typhae.
2. The traditional Chinese medicine composition according to claim 1, wherein the formula of each raw material is: 3 to 120 parts of astragalus, 3 to 30 parts of cassia twig, 3 to 70 parts of medlar, 3 to 30 parts of pipewort and 3 to 30 parts of raw pollen typhae.
3. The traditional Chinese medicine composition according to claim 1, wherein the formula of each raw material is: 3 to 60 parts of astragalus, 3 to 15 parts of cassia twig, 3 to 30 parts of medlar, 3 to 15 parts of pipewort, and 3 to 15 parts of raw pollen typhae.
4. The traditional Chinese medicine composition according to claim 1, wherein the formula of each raw material is: 30g of astragalus, 9g of cassia twig, 9g of medlar, 9g of pipewort and 9g of raw pollen typhae.
5. The traditional Chinese medicine composition according to claim 1, wherein the formula of each raw material is: 15g of astragalus, 6g of cassia twig, 9g of medlar, 9g of pipewort and 9g of raw pollen typhae.
6. The traditional Chinese medicine composition according to claim 1, wherein the traditional Chinese medicine composition is prepared into decoction, granules, capsules, tablets, powder, pills or oral liquid.
7. The use of a Chinese medicinal composition according to any one of claims 1 to 6 in the manufacture of a medicament for the treatment of non-proliferative diabetic retinopathy.
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| CN112717062A (en) * | 2021-03-04 | 2021-04-30 | 上海中医药大学附属龙华医院 | Traditional Chinese medicine composition for treating diabetic retinopathy |
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