CN110538214A - Composition containing astragalus root, kudzu vine root and erigeron breviscapus and application thereof - Google Patents

Abstract

The application provides an application of a composition containing astragalus, kudzuvine root and erigeron breviscapus in preparing a medicament for treating or preventing macular edema of an individual.

Description

Composition containing astragalus root, kudzu vine root and erigeron breviscapus and application thereof

Technical Field

The application relates to a composition containing astragalus, kudzuvine root and erigeron breviscapus and application thereof, in particular to application of the composition containing the astragalus, the kudzuvine root and the erigeron breviscapus in treating macular region diseases.

Background

The macula is a shallow funnel-shaped fovea of about 2mm in diameter located at the posterior pole of the retina, with a fovea at the center of the fovea being the fovea. The macular area is the most important part of the retina for generating visual signals, and any pathological changes of the macula can affect the vision and even lead to the serious consequences of blindness. With the development and progress of medicine, the harm of traditional blindness-causing eye diseases such as cataract is greatly reduced, and the serious influence of macular diseases on vision is particularly remarkable.

Macular edema is a pathological process caused by different intraocular pathological changes, and can be secondary to various diseases such as diabetes, uveitis, retinal vein occlusion, cataract surgery and the like. Clinical macular edema refers to accumulation of fluid among cells in the central part of the macula, which can seriously threaten the central vision of patients and is the main reason of vision loss caused by various eye diseases. The long-standing presence of macular edema eventually leads to irreversible retinal atrophy and fibrosis, resulting in permanent loss of central vision.

Current methods of treating diabetic macular edema include systemic treatments to control blood glucose, blood pressure, and blood lipids in patients, as well as ocular treatments. The eye treatment method mainly comprises operation treatment, laser photocoagulation treatment and drug treatment. The drug therapy mainly involves injecting glucocorticoid or anti-VEGF preparation into eyes, wherein the commonly used anti-VEGF preparation is Abelicept, Corbescept, ranibizumab and the like. Currently, the recommended treatment methods in domestic and foreign guidelines are laser photocoagulation treatment and intraocular injection of anti-VEGF preparations. However, laser photocoagulation is traumatic and the effect is not sustained. The intraocular injection of the anti-VEGF preparation has high cost and short duration of therapeutic effect, which lasts only 1-3 months, and requires repeated intraocular injections, which causes risks of intraocular infection, increased intraocular pressure, etc., and thus, patients suffer great pain.

The traditional Chinese medicine is gradually used for treating various ophthalmic diseases due to higher safety, but due to the complex natural medicinal components and different effects possibly caused by the compatibility of medicines, no relevant report about effective treatment of macular edema, particularly diabetic macular edema by using the traditional Chinese medicine as a raw material in a compatibility manner exists at present.

Disclosure of Invention

In a first aspect, the present application provides the use of a composition comprising astragalus, pueraria and erigeron breviscapus in the manufacture of a medicament for treating or preventing macular edema in a subject.

In a second aspect, the present application provides a method of treating or preventing macular edema comprising administering to a subject a therapeutically or prophylactically effective amount of a composition comprising astragalus, puerariae radix and erigeron breviscapus.

In a third aspect, the present application provides a composition comprising astragalus, pueraria and erigeron breviscapus for treating or preventing macular edema.

In a fourth aspect, the present application provides a composition comprising astragalus root, pueraria root and erigeron breviscapus.

In certain embodiments, the macular edema described above is cystoid macular edema. In a preferred embodiment, the macular edema is diabetic macular edema.

In certain embodiments, the above composition is formulated with a pharmaceutically acceptable carrier into a pharmaceutically acceptable dosage form, preferably a capsule, oral liquid, powder, tablet, granule, pill, syrup, or eye drop, more preferably a capsule.

in certain embodiments, the above composition is administered orally, via eye drops, enema, subcutaneously, intramuscularly or intraperitoneally, preferably, the composition is administered orally.

in certain embodiments, the composition is administered in a dose of 30 to 100mg/kg body weight, preferably 50 to 70mg/kg body weight, per day.

In certain embodiments, the composition is for oral administration 1 to 3 times per day, e.g., 2 or 3 times per day.

In certain embodiments, the composition is administered for a duration of 1 to 52 weeks, preferably 12-24 weeks, e.g., 24 weeks.

In certain embodiments, the composition comprises the following raw materials in parts by weight: 10-40 parts of astragalus root, 10-30 parts of kudzu root and 10-30 parts of erigeron breviscapus.

In certain embodiments, the above composition comprises the following active ingredients in parts by weight: 1-10 parts of astragalus extract, 50-125 parts of kudzu root extract and 20-60 parts of breviscapine extract.

In some embodiments, the medicament is prepared from raw materials of astragalus, kudzuvine root and erigeron breviscapus or water or organic solvent extracts of the astragalus, the kudzuvine root and the erigeron breviscapus as active ingredients and a pharmaceutically acceptable carrier. In some embodiments, the astragalus, the kudzuvine root and the erigeron breviscapus are weighed according to a certain weight ratio to respectively prepare extracts of the astragalus, the kudzuvine root and the erigeron breviscapus, and other active ingredients or pharmaceutically acceptable carriers are added according to a preparation method of a conventional Chinese medicinal preparation to prepare different preparations, such as capsules, tablets, granules, pills, eye drops and the like.

Drawings

Fig. 1 shows the change in eye vision of macular edema patients as measured by Optical Coherence Tomography (OCT), showing the change in Best Corrected Vision (BCVA) after each group of patients received different doses of the composition of the present application, where the diamonds are the high dose group (n ═ 7), the squares are the medium dose group (n ═ 11), the right triangles are the low dose group (n ═ 7), and the forks are the placebo group (n ═ 13).

Figure 2 shows the change in vision of the affected eye with CRT greater than 270 μm when tested by OCT showing an improvement in vision of the affected eye by 5 characters after treatment with a high dose (n-24), a medium dose (n-15), a low dose (n-8) of the composition and placebo (n-12), respectively, wherein the P value of the medium dose group is 0.058 and the P value of the high dose group is 0.130 relative to the placebo group.

Figure 3 is an OCT of the change in foveal thickness of the affected eye of patients with macular edema showing the change in foveal thickness in μm for each group of affected eyes after 12 weeks and 24 weeks of high dose, medium dose, low dose composition and placebo treatment, respectively. In the bar graphs showing 12 weeks and 24 weeks, from left to right, there were a high dose group (n ═ 7), a medium dose group (n ═ 11), a low dose group (n ═ 6), and a placebo group (n ═ 10).

Detailed Description

The inventors of the present application have unexpectedly found that a composition comprising astragalus, pueraria and erigeron breviscapus is capable of treating or preventing macular edema, such as diabetic macular edema.

Unless otherwise indicated, all terms used in this application have the meanings commonly understood by those skilled in the art.

The application provides application of a composition containing astragalus, kudzuvine root and erigeron breviscapus in preparing a medicine for treating macular edema.

In certain embodiments, the macular edema is cystoid macular edema. In certain embodiments, the macular edema is diabetic macular edema.

Cystoid macular edema is a common fundus disease, but it is not an independent disease, but a manifestation of many fundus diseases in the macular region. Common diseases causing cystoid macular edema are: retinal vein occlusion, diabetic retinopathy, retinal vasculitis, macular retinal foremembrane, retinal telangiectasia or Coats disease, uveitis, cataracts, or other internal eye surgery, and the like.

Diabetic Macular Edema (DME) refers to the thickening or hard exudative deposition of the retina due to the accumulation of extracellular fluid within one disc diameter of the fovea of the macula caused by diabetes. Diabetic macular edema is a common cause of visual impairment in diabetic patients.

As used herein, "treating" includes inhibiting, curing, reducing, alleviating, or delaying macular edema and related symptoms.

In some embodiments, the compositions of the present application are formulated into a pharmaceutically acceptable dosage form, preferably eye drops, oral liquid, capsules, tablets or granules, more preferably capsules, together with a pharmaceutically acceptable carrier.

As used herein, "pharmaceutically acceptable carrier" refers to a carrier that does not interfere with the effectiveness of the biological activity of the active ingredient, including those conventionally used in the pharmaceutical arts. The pharmaceutically acceptable carrier of the present application may be a solid or a liquid, including pharmaceutically acceptable excipients, buffers, emulsifiers, stabilizers, preservatives, diluents, encapsulating agents, fillers, and the like. For example, pharmaceutically acceptable buffers include phosphates, acetates, citrates, borates, carbonates, and the like.

The compositions of the present application may be presented in unit dosage form and may be prepared by any of the methods well known in the pharmaceutical arts. All methods include the step of bringing into association the active ingredients of the present application with one or more pharmaceutically acceptable carriers. Generally, compositions are prepared by combining the active ingredient with a liquid carrier, a solid carrier, or both, and then shaping the prepared product as desired. The particular formulation method will depend on the route of administration chosen. In some embodiments, the compositions can be manufactured by conventional mixing, dissolving, granulating, dragee-making, milling, emulsifying, encapsulating, entrapping or lyophilizing processes.

In some embodiments, the composition is administered orally, eye drops, enema, subcutaneously, parenterally, intravenously, intraarterially, intracranially, intrathecally, intraperitoneally, topically, intranasally, or intramuscularly. In a specific embodiment, the combination is administered orally.

In some embodiments, for oral administration, a composition such as the present application can be formulated with a pharmaceutically acceptable carrier as a capsule, tablet, pill, lozenge, liquid, gel, syrup, slurry, suspension, or the like. For oral solid formulations, such as powders, capsules and tablets, suitable excipients include fillers, for example sugars, such as lactose, sucrose, mannitol and sorbitol; cellulose preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth, methyl cellulose, carboxypropyl methyl cellulose, sodium carboxymethylcellulose and/or povidone; granulating agents, binders and the like. If desired, disintegrating agents can be added, such as cross-linked polyvinylpyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate. If desired, the solid dosage form may be sugar coated or enteric coated using standard techniques. For oral liquid preparations such as suspensions, elixirs and solutions, suitable carriers, excipients or diluents include water, glycerol, oils, alcohols. In addition, a flavoring agent, a preservative, a coloring agent, and the like may be added.

In certain embodiments, the compositions of the present application are administered at a dose of 30 to 100mg/kg body weight, preferably 40-80mg/kg body weight, more preferably 50-70mg/kg body weight, e.g., 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100mg/kg body weight or a dose between any two of the foregoing, and the like, administered daily.

In some embodiments, the composition is administered 1, 2, 3, 4, or more times per day, the composition may also be administered less than 1 time per day, e.g., 1 time per day every 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14, or 1 time per 1 or 2 weeks, or a range bounded by any two of the foregoing values. In some embodiments, the number of daily administrations is constant (e.g., 2 or 3 times daily). In other embodiments, the number of administrations is variable. The number of administrations may vary depending on the effectiveness of the composition, the side effects observed, the particular route of administration, the particular characteristics of the individual, history and risk factors (e.g., age, weight, general health, etc.), another medication-related variation, or the dosage form.

in some embodiments, the composition is administered for a duration of 1-52 weeks, e.g., 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 36, 48, or 52 weeks, or a number of weeks between any two of the foregoing, or about the period of time. In some embodiments, the composition is administered continuously for 12 weeks, 16 weeks, 18 weeks, 20 weeks, 22 weeks, 24 weeks, or more. In some embodiments, administration of the composition is continued until the individual no longer requires treatment.

In another aspect, the present application provides a method of treating or preventing macular edema, comprising administering to a subject a therapeutically effective amount or a prophylactically effective amount of a composition comprising astragalus, puerariae radix and erigeron breviscapus.

In yet another aspect, there is provided a use of a therapeutically effective amount or a prophylactically effective amount of a composition comprising astragalus, pueraria and erigeron breviscapus in treating or preventing macular edema in a subject.

as used herein, a "therapeutically effective amount" or a "prophylactically effective amount" may be determined on a case-by-case basis and can be readily determined by one of ordinary skill in the art based on the amount of drug actually required, e.g., based on the weight, age, and condition of the patient. When the compositions contain a pharmaceutically acceptable carrier, they may be mixed according to conventional methods in the pharmaceutical art to prepare the desired drug.

In some embodiments, the present composition comprising astragalus, pueraria and erigeron breviscapus is capable of improving vision of an affected eye of a patient with macular edema. In a specific embodiment, the macular edema is diabetic macular edema. In a specific embodiment, the efficacy of the composition for improving the vision of eyes with macular edema presents a certain dose-effect relationship.

In some embodiments, the composition comprising astragalus, pueraria and erigeron breviscapus herein can be used to reduce the thickness of and/or reduce the volume of the macular fovea of an affected eye of an individual with macular edema, thereby improving the degree of macular edema. In a specific embodiment, the subject has diabetic macular edema. In a specific embodiment, the individual is at risk for diabetic macular edema. In particular embodiments, the effect of the compositions of the present application in reducing the thickness of the fovea macula and/or reducing the volume of the fovea macula exhibits a dose-effect relationship. In particular embodiments, the effect of the compositions of the present application to reduce the foveal thickness is increasingly significant with an extended course of treatment.

In some embodiments, the composition comprising astragalus, pueraria and erigeron breviscapus of the present application is capable of reducing intraocular pressure in an affected eye of an individual with macular edema. In a specific embodiment, the subject has diabetic macular edema. In a specific embodiment, the individual is at risk for diabetic macular edema. In a specific embodiment, the difference between the effect of the composition of the present application in reducing ocular pressure in eyes with macular edema and placebo treated group becomes more significant over time.

In some embodiments, the composition comprising astragalus, pueraria and erigeron breviscapus of the present application has no significant difference in adverse event and adverse reaction incidence rate compared to placebo treated group in treating macular edema of an individual, indicating that the medicament of the present application has no significant toxic or side effect and high safety in treating macular edema.

"individual," as used herein, refers to mammals, including primates and non-primates, such as humans, apes, monkeys, cows, horses, pigs, sheep, goats, dogs, cats, and rodents, such as rats and mice. In yet another aspect, the present application provides a composition comprising astragalus, pueraria and erigeron breviscapus. In a specific embodiment, the above composition is used to treat or prevent macular edema in an individual.

In certain embodiments, the compositions of the present application are prepared from the following raw materials in parts by weight: 10-40 parts of astragalus root, 10-30 parts of kudzu root and 10-30 parts of erigeron breviscapus.

In certain embodiments, the compositions of the present application are prepared from the following raw materials in parts by weight: 20-30 parts of astragalus membranaceus, 20-40 parts of kudzu root and 20-30 parts of erigeron breviscapus.

In certain embodiments, the compositions of the present application are prepared from the following raw materials in parts by weight: 20 parts of astragalus root, 30 parts of kudzu root and 20 parts of erigeron breviscapus.

In some embodiments, the composition of the present application is prepared by using raw materials of astragalus, pueraria and erigeron breviscapus or water or organic solvent extracts as active ingredients and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.

In certain embodiments, the composition comprises the following components in parts by weight: 1-10 parts of astragalus extract, 50-125 parts of kudzu root extract and 20-60 parts of breviscapine extract.

in certain embodiments, the composition comprises an extract of astragalus membranaceus, an extract of pueraria lobata, and an extract of erigeron breviscapus, wherein the extract of pueraria lobata contains not less than 60% total isoflavones by puerarin and not less than 20% puerarin; the radix astragali extract contains total saponins not less than 50% calculated by astragaloside IV and not less than 5% of astragaloside IV; the herba Erigerontis extract contains total flavone not less than 35% calculated by rutin, and scutellarin not less than 3%.

In certain embodiments, the composition comprises, by weight: 1-10 parts of astragalus extract, 50-125 parts of kudzu root extract and 20-60 parts of breviscapine extract.

In certain embodiments, the composition comprises, by weight: 1 part of astragalus extract, 70 parts of kudzu root extract and 25 parts of breviscapine extract.

In a specific embodiment, the preparation method of the composition containing astragalus, kudzuvine root and erigeron breviscapus comprises the following steps:

a. Weighing the following raw materials in parts by weight:

10-40 parts of astragalus root, 10-30 parts of kudzu root and 10-30 parts of erigeron breviscapus;

b. Pulverizing radix Puerariae into coarse powder, extracting with 60-95% ethanol, filtering, mixing filtrates, recovering ethanol, concentrating, passing through macroporous adsorbent resin column, eluting with water, discarding water eluate, eluting with 10-95% ethanol, collecting ethanol eluate, recovering ethanol, concentrating into soft extract, drying under reduced pressure, and pulverizing into fine powder to obtain radix Puerariae extract;

c. Pulverizing radix astragali into coarse powder, extracting with 60-95% ethanol under reflux, filtering, mixing filtrates, recovering ethanol, concentrating, adding sodium hydroxide until the alkali content is 2-5%, adding n-butanol, dynamically extracting for 2-5 times, mixing n-butanol solutions, washing with 2-5% sodium hydroxide solution, washing with water, discarding washing solution, mixing n-butanol solutions, concentrating under reduced pressure to near dryness, adding acetone, grinding, washing to light color, collecting precipitate, drying under reduced pressure, and pulverizing into fine powder to obtain radix astragali extract;

d. Decocting herba Erigerontis with water, mixing decoctions, filtering, concentrating, passing through macroporous adsorbent resin column, eluting with water, removing water eluate, eluting with 10-95% ethanol, collecting ethanol eluate, recovering ethanol, concentrating into soft extract, drying under reduced pressure, and pulverizing into fine powder to obtain herba Erigerontis extract;

e. Mixing the radix astragali extract, radix Puerariae extract and herba Erigerontis extract prepared in steps b, c and d, adding pharmaceutically acceptable vehicle, and making into pharmaceutically common preparation.

In some embodiments, in step a, the raw materials may be 20-30 parts by weight of astragalus, 20-40 parts by weight of pueraria root and 20-30 parts by weight of erigeron breviscapus. Wherein, astragalus root can be 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 parts, kudzuvine root can be 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 or 40 parts, erigeron breviscapus can be 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 parts. In a specific embodiment, the raw materials comprise 20 parts by weight of astragalus, 30 parts by weight of kudzu root and 20 parts by weight of erigeron breviscapus.

Within the reasonable range of the raw material selection of the medicine, the medicine can be prepared into a preparation commonly used in pharmacy according to the extraction and treatment method of the medicine. For example, the obtained dry fine powder with the three medicines as main components is prepared into different dosage forms such as tablets, granules, pills, capsules, eye drops and the like by adding auxiliary materials according to the preparation method of the conventional Chinese medicine dosage form.

in some embodiments, 30kg of astragalus, 40kg of kudzuvine root and 30kg of erigeron breviscapus are weighed and directly pulverized to obtain powder.

In some embodiments, 1kg of the above radix astragali extract, 50kg of the above radix puerariae extract and 30kg of the above herba erigerontis extract are taken, mixed, added with starch, granulated, added with magnesium stearate, and tabletted to obtain tablets.

In some embodiments, 10kg of the astragalus extract, 125kg of the kudzu root extract and 60kg of the erigeron breviscapus extract are mixed, added with starch, granulated and directly encapsulated to obtain capsules.

In some embodiments, 2kg of the astragalus extract, 80kg of the pueraria extract and 40kg of the erigeron breviscapus extract are mixed, added with starch, granulated and directly encapsulated to obtain the medicinal granules.

In some embodiments, 30kg of astragalus, 40kg of kudzuvine root and 30kg of erigeron breviscapus are extracted according to the method, 20kg of rehmannia, 20kg of medlar, 15kg of cassia seed and 20kg of motherwort fruit are added with water for decoction, concentrated, mixed, added with starch, granulated, added with magnesium stearate and tableted to obtain the tablet.

The process for the preparation of the compositions of the present application can also be found in chinese patent CN100594913C, which is incorporated herein by reference in its entirety.

Throughout the description and claims of this application, the words "comprise," "comprising," and "contain" mean "including but not limited to," and are not intended to exclude other moieties, additives, components, or steps.

It should be understood that features, characteristics, components or steps described in a particular aspect, embodiment or example of the present application may be applied to any other aspect, embodiment or example described herein unless incompatible therewith.

Unless otherwise indicated, all numbers expressing features, terms, quantities, parameters, properties, terms, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about. As used herein, the term "about" means that the defined characteristic, item, quantity, parameter, property, or term encompasses a range of plus or minus ten percent of the value of the characteristic, item, quantity, parameter, property, or term. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and claims are approximations that may vary. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical indication should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

The above disclosure generally describes the present application, which is further exemplified by the following examples. These examples are described merely to illustrate the present application and do not limit the scope of the present application. Although specific terms and values are employed herein, they are to be understood as exemplary and not limiting the scope of the application. Unless otherwise indicated, the experimental methods and techniques described herein are those well known to those skilled in the art.

Examples

the following examples are provided merely to illustrate some embodiments of the present application and are not intended to be limiting in any way.

the methods used in the following examples are conventional methods unless otherwise specified. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

Example 1: preparation method of composition containing astragalus root, kudzu vine root and erigeron breviscapus

Weighing 30kg of radix puerariae, 20kg of erigeron breviscapus and 20kg of radix astragali, crushing the radix puerariae into coarse powder, heating and refluxing the coarse powder for twice by using 60% ethanol for 1 hour each time, filtering, combining filtrates, recovering the ethanol, appropriately concentrating, adding the concentrated solution onto a treated macroporous adsorption resin column, eluting by water, removing water eluent, continuously eluting by using 70% ethanol, collecting ethanol eluent, concentrating the ethanol eluent under reduced pressure into thick paste, drying under reduced pressure, and crushing the thick paste into fine powder to obtain the radix puerariae extract;

Pulverizing radix astragali into coarse powder, extracting with 90% ethanol under reflux for three times, each for 1 hr, filtering, mixing filtrates, recovering ethanol, concentrating, adding sodium hydroxide until the alkali content is 5%, adding n-butanol, dynamically extracting for 2 times, mixing n-butanol solutions, washing with 5% sodium hydroxide solution for 1 time, washing with water for 2 times, discarding the washing solution, mixing n-butanol solutions, concentrating under reduced pressure to near dryness, adding acetone, grinding and washing to light color, collecting precipitate, drying under reduced pressure, and pulverizing into fine powder to obtain radix astragali extract;

Decocting herba Erigerontis with water for three times, each for 1 hr, mixing decoctions, filtering, concentrating, loading onto treated macroporous adsorbent resin column, eluting with water, discarding water eluate, eluting with 70% ethanol, collecting ethanol eluate, recovering ethanol, concentrating into soft extract, drying under reduced pressure, and pulverizing into fine powder to obtain herba Erigerontis extract;

Mixing the above three fine powders with carboxymethyl starch sodium, hydroxypropyl cellulose, silica gel micropowder and magnesium stearate, and making into capsule to obtain composition containing radix astragali, radix Puerariae and herba Erigerontis.

Example 2: therapeutic effect of the composition of the present application on diabetic macular edema

2.1 design of test protocol

test population

Selecting patients meeting the diagnosis standard of diabetic retinopathy (qi and yin deficiency and blood stasis blocking collaterals); the subjects were informed and voluntarily signed an informed consent. Subjects were divided into A, B, C and D four groups.

Dosing regimens

The dose per group was as follows, with a course of treatment of 24 weeks:

group A was a high dose group, to which 4 capsules prepared according to the method of example 1 were administered 3 times a day at a daily dose of 66mg/kg body weight/day;

Group B was a medium dose group, to which 2 capsules prepared according to the method of example 1 were administered 3 times a day at a daily dose of 33mg/kg body weight/day;

Group C was a low dose group, to which 1 capsule prepared according to the method described in example 1 was administered 3 times a day at a daily dose of 16.5mg/kg body weight/day; and

Group D is placebo group, and the preparation without any active pharmaceutical ingredient prepared from rice is administered 3 times a day at a daily dose of 66mg/kg body weight/day.

Basic and combination prescriptions

During the test period, the blood sugar of the subject is kept stable (HbAlc ≦ bA). The basic hypoglycemic medicine adopts biguanides, sulfonylureas, insulin and insulin sensitizer;

During the test period, all Chinese and western medicines with the same effect as the test medicines are forbidden, including anti-platelet medicines such as clopidogrel sulfate and the like, anticoagulant medicines such as aspirin and the like, fibrinolytic medicines such as urokinase and the like, western medicines for treating diabetic retinopathy and traditional Chinese medicines with similar effects.

Evaluation criteria

Refer to the "clinical research guiding principle of new Chinese medicine for treating diabetic retinopathy" in the "clinical research guiding principle of new Chinese medicine" of the first edition of New Chinese medicine clinical research guiding principle of the Chinese medicine science and technology publishing agency, 2002, 5 months. The fundus photography and fundus fluorescence angiography image are blindly read by a person special in the center of the film reading.

Optical Coherence Tomography (OCT)

An optical coherence tomography scan is performed on an affected eye of a macular edema patient, wherein indices of the optical coherence tomography scan include foveal thickness and neuroepithelial volume (refer to 6mm zone thickness and neuroepithelial volume).

Judgment standard for vision correction effect

The actual identified numbers of the EDTRS optotypes are used for analysis.

2.2 enrollment and Baseline comparability analysis results

A total of 201 patients were enrolled in the study, see Table 1.

TABLE 1

The difference in the rejection rate of the four groups was not statistically significant (P-0.4510).

Group a 3, group B1, group C1 and group D3 had poor compliance, and the difference in the incidence of poor compliance in the four groups was not statistically significant (P0.5612).

The population characteristics, vital signs, accompanying diseases and other aspects of the four groups of patients are distributed similarly, and the differences among various indexes except the lipid-lowering treatment have no statistical significance.

All patients entering the FAS analysis set have no statistical significance for differences of all indexes in aspects of ophthalmology examination, film reading results, optical coherence tomography examination, symptom sign quantitative grading and the like of four groups of patients' baselines except for the existence of a lot of thready and weak thready pulse, and all groups are prompted to have good comparability.

2.3 therapeutic Effect of the compositions of the present application on macular edema

2.3.1 the composition of the present application improves vision in macular edema affected eyes,

In this example, four groups of patients with clinically diagnosed macular edema in the target eye were examined for ocular vision, 7 in the high dose group, 11 in the medium dose group, 7 in the low dose group, and 13 in the placebo group. As a result, as shown in FIG. 1, the patients in the high dose group and the middle dose group had a significant improvement in their visual acuity after taking the drugs for 12 weeks and 24 weeks, for example, at 24 weeks, the visual acuity improvement characters of the high and middle dose groups reached 5.71 and 4.91, respectively, while the visual acuity improvement characters of the placebo group were only 1.69.

The data in figure 1 demonstrate that the compositions of the present application are capable of improving vision in macular edema patients, and exhibit certain dose and time dependent effects.

2.3.2 the Effect of the composition of the present application on improving the Vision of an affected eye having a foveal thickness of greater than 270 μm when administered to a patient

In this example, four groups of macular edema patients were examined for their affected eyes by optical coherence tomography to obtain the condition of foveal thickness (CRT). And respectively treating each group of affected eyes with CRT larger than 270 microns in group with corresponding dose, and counting the ratio of improving the vision of each group of affected eyes by 5 characters after 24 weeks of treatment. The results are shown in FIG. 2.

As can be seen from fig. 2, the composition of the present application can significantly improve the vision of macular edema with CRT greater than 270 μm, wherein the ratio of 5 characters is significantly higher in the high dose group and the medium dose group than in the placebo group. For example, the high dose group (24 cases) increased the rate of 5 characters by up to 42%, and the medium dose group (15 cases) increased the rate of 5 characters by up to 53%, which is much higher than the rate of 17% in the placebo group. The P-value for the medium dose group was 0.058 and the P-value for the high dose group was 0.130 relative to the placebo group by applying the stata chi-square test.

2.3.3 Effect of the compositions of the present application on the thickness of the fovea macula

in this example, four groups of target eyes were examined by optical coherence tomography before treatment and after 12 and 24 weeks of treatment for the affected eyes with clinically diagnosed macular edema to obtain the change in the foveal thickness of the macula, wherein 7 patients were in the high dose group, 11 patients were in the medium dose group, 6 patients were in the low dose group, and 10 patients were in the placebo group. The results are shown in FIG. 3. And processing data by adopting SAS software. The comparison before and after treatment in the group was carried out by the symbol rank test, and the comparison between the four groups after treatment (high, medium and low dose group and placebo group) was carried out by the Kruskal-Wallis test.

As can be seen from FIG. 3, the change in fovea thickness represents a dose-effect relationship, the high dose group can significantly reduce the fovea thickness of the affected eye of patients with macular edema, and the medium and low dose groups also have a certain effect. The difference between the treatment group and the placebo group increased with increasing treatment duration (decreased P-value), for example 0.4431 at 12 weeks and 0.1530 at 24 weeks.

in addition, the inventors have expanded the number of samples and investigated the effect of the compositions of the present application on the thickness of the fovea in the affected eye of a larger number of diabetic retinopathy patients, including the patients mentioned above, with results similar to those described above in relation to macular edema alone: there was a dose-response trend, with more distinct differences between groups and a trend of increasing differences (decreasing P-value) over time, especially consistent with the high dose and placebo.

The inventors have further investigated the effect of the compositions of the present application on intraocular pressure in macular edema affected eyes. The results show that the composition of the application can obviously reduce the intraocular pressure of patients with macular edema and show a certain dose-effect relationship on the whole, wherein the intraocular pressure of patients with eyes is obviously reduced after the patients in a high-dose group take the medicine for 12 weeks and 24 weeks.

The combination of the above experimental results shows that the composition of the present application has good effect on treating diabetic macular edema. The above results also demonstrate the effect of the compositions of the present application in improving the intraocular microcirculation. Since the intraocular pressure, the foveal thickness and the volume are all key indexes for representing the edema state of the eyeball, the reduction of the intraocular pressure combined with the change of the foveal thickness or the volume indicates that the edema of the eyeball is improved, and the improvement effect tends to be enhanced along with the time progress.

2.4 evaluation of safety

After the medicine is taken, the body temperature, blood pressure, pulse, respiration and laboratory indexes of some patients are abnormal in normal rotation and abnormal in abnormal rotation.

Incidence of adverse events the incidence of adverse events was 22.64% in group a, 26.00% in group B, 14.00% in group C, and 19.15% in group D, with no statistical significance in the differences in the four groups as analyzed by the CMH test (P-0.4910).

Incidence of severe adverse events 1.89% in group a, 0.00% in group B, 2.00% in group C, and 0.00% in group D, with four groups of differences not statistically significant (P ═ 0.5942).

Incidence of adverse reactions 3.77% in group a, 2.00% in group B, 0.00% in group C, and 4.26% in group D, with no statistical significance for the differences in the four groups (P ═ 0.5185).

Four groups of differences of various adverse events and adverse reaction incidence rates have no statistical significance, which shows that the medicine has no obvious toxic or side effect and high safety when being used for treating macular edema.

Various modifications and equivalents may be made to the embodiments disclosed herein without departing from the spirit and scope of the disclosure. Unless the context indicates otherwise, any feature, step, or embodiment of an embodiment of the present disclosure may be used in combination with any other feature or embodiment.

Claims (10)

1. Use of a composition comprising astragalus, pueraria and erigeron breviscapus in the preparation of a medicament for treating or preventing macular edema in a subject.

2. The use of claim 1, wherein the macular edema is cystoid macular edema.

3. The use of claim 1 or 2, wherein the macular edema is diabetic macular edema.

4. The use as claimed in any one of claims 1 to 3, wherein the composition comprises the following raw materials of astragalus, pueraria and erigeron breviscapus in weight ratio: 10-40 parts of astragalus root, 10-30 parts of kudzu root and 10-30 parts of erigeron breviscapus; preferably, the astragalus is 20 parts, the kudzuvine root is 30 parts, and the erigeron breviscapus is 20 parts.

5. The use as claimed in any one of claims 1 to 3, wherein the composition is prepared from active ingredients comprising an extract of Astragalus membranaceus, an extract of Pueraria lobata and an extract of Erigerontis; preferably, the weight ratio of the active ingredients is as follows: 1-10 parts of astragalus extract, 50-125 parts of kudzu root extract and 20-60 parts of breviscapine extract.

6. the use according to any one of claims 1 to 5, wherein the composition is formulated with a pharmaceutically acceptable carrier into a pharmaceutically acceptable dosage form, preferably a capsule, oral liquid, powder, tablet, granule, pill, syrup or eye drop, more preferably a capsule.

7. The use according to any one of claims 1 to 6, wherein the composition is administered orally, via eye drops, enema, subcutaneously, intramuscularly or intraperitoneally; preferably, the composition is administered orally.

8. The use according to any one of claims 1 to 7, wherein the composition is administered in a dose of 30 to 100mg/kg body weight, preferably 50 to 70mg/kg body weight, per day.

9. The use of any one of claims 1-8, wherein the composition is administered orally 2 or 3 times per day.

10. The use according to any one of claims 1 to 9, wherein the composition is administered for a duration of 1 to 52 weeks, preferably 12 to 24 weeks.