CN117243947A - Application of daphnetin and combination containing daphnetin in preparation of diabetes complication medicaments - Google Patents

Application of daphnetin and combination containing daphnetin in preparation of diabetes complication medicaments Download PDF

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CN117243947A
CN117243947A CN202311158734.8A CN202311158734A CN117243947A CN 117243947 A CN117243947 A CN 117243947A CN 202311158734 A CN202311158734 A CN 202311158734A CN 117243947 A CN117243947 A CN 117243947A
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diabetic
daphnetin
pharmaceutically acceptable
medicament
solvate
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张俊
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Jilin Xidian Pharmaceutical Technology Development Co ltd
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Jilin Xidian Pharmaceutical Technology Development Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A61K31/37—Coumarins, e.g. psoralen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P27/12—Ophthalmic agents for cataracts
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

The invention relates to application of daphnetin and a combination containing daphnetin in preparation of a medicament for treating diabetic complications, and the daphnetin or pharmaceutically acceptable salt or solvate thereof has good treatment effect when being used for treating the diabetic complications. The invention also provides application of daphnetin or pharmaceutically acceptable salt or solvate thereof and a plurality of other active medicaments in combination for preparing medicaments for treating diabetic complications, a pharmaceutical composition containing daphnetin or pharmaceutically acceptable salt or solvate thereof and a preparation method of daphnetin or pharmaceutically acceptable salt or solvate and a plurality of other active medicaments. When the daphnetin and the other active medicaments are combined for treating the diabetic complications, the daphnetin has a synergistic effect, and the curative effect on the diabetic complications can be obviously improved.

Description

Application of daphnetin and combination containing daphnetin in preparation of diabetes complication medicaments
Technical Field
The invention relates to the technical field of medicines, in particular to application of daphnetin and a combination containing daphnetin in preparation of a medicine for diabetic complications.
Background
Diabetes is a metabolic disorder syndrome caused by the hypofunction of the pancreas islet of the organism, insulin resistance and the like, threatens the health of human beings and becomes serious. The biggest hazard faced by diabetics is the many complications they induce. Due to its high disability and mortality rate, diabetic complications have become one of the major threats to the health and longevity of most national residents.
Diabetes can lead to hyperglycemia and disturbed carbohydrate metabolism, accompanied by long-term damage and dysfunction or loss of different organs (especially blood vessels, nerves, heart, muscles, eyes, kidneys), and associated diabetic complications. Diabetes complications are related to various diseases and are the result of the combined actions of vascular lesions, nervous system lesions, metabolic disorders and the like, and are commonly: diabetic skin disorders, peripheral and central neuropathy, microvascular complications (including diabetic nephropathy and retinopathy), macrovascular complications (such as coronary heart disease, peripheral vascular disease and cerebrovascular disease), diabetic foot and wounds of diabetic patients are difficult to heal, and the like.
Prevention and treatment of diabetic complications are important and difficult points in the field of diabetes. Current methods for alleviating diabetic complications rely on lowering blood glucose, e.g. by preferentially selecting hypoglycemic agents with cardiovascular protective effects. However, in general, no satisfactory clinical effect is currently achieved on the prevention and treatment of diabetic complications.
Disclosure of Invention
The invention aims to provide daphnetin and application of a combination containing daphnetin in preparation of a drug for diabetic complications.
To this end, in a first aspect, the invention provides the use of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of diabetic complications.
In some embodiments, the medicament has daphnetin, or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient.
In some embodiments, the daphnetin, or a pharmaceutically acceptable salt or solvate thereof, is present in the medicament in an amount effective to treat the diabetic complication.
In some embodiments, the content of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient in the medicament is 0.1-99.9% (w/w).
In some embodiments, the diabetic complication is a stage i, ii, iii, or iv diabetic complication.
In some embodiments, the diabetic complication is selected from the group consisting of: diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic cataract, diabetic bladder disease, diabetic keratopathy, diabetic dermatological lesions, diabetic microangiopathy, diabetic peripheral neuropathy, diabetic co-hyperlipidemia, myocardial infarction, macular edema, impaired nerve conduction, diabetic wounds.
In some embodiments, the drug is an orally administered agent, an injectable agent, an implantable agent, a spray administered agent, or an inhaled agent.
In some embodiments, the dosage form of the medicament includes, but is not limited to, injection, tablet, granule, capsule, drop pill, sustained release formulation, oral liquid formulation, powder or gel.
In some embodiments, the medicament further comprises a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
In a second aspect of the invention, there is provided the use of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in combination with other active agents for the manufacture of a medicament for the treatment of diabetic complications; the other active agents include at least one selected from the group consisting of: biguanides, insulin; angiotensin Converting Enzyme Inhibitor (ACEI), angiotensin receptor Antagonist (ARB), statins, antiplatelet aggregation drugs, prostaglandin E2, pentoxifylline, anisodamine, methyl vitamin B12, neurotrophic factor, C Peptide (C-Peptide), a-lipoic acid, heart vein relaxing capsules, red ginseng cordyceps capsules, ginkgo dipyridamole.
In some embodiments, the biguanide drug comprises metformin.
In some embodiments, the angiotensin converting enzyme inhibitor comprises at least one selected from the group consisting of: captopril, enalapril, perindopril, benazepril, imidapril, fosinopril.
In some embodiments, the angiotensin receptor antagonist comprises at least one selected from the group consisting of: valsartan, irbesartan, losartan, candesartan, telmisartan, olmesartan.
In some embodiments, the statin comprises at least one selected from the group consisting of: atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, mevastatin.
In some embodiments, the anti-platelet aggregation drug comprises at least one selected from the group consisting of: aspirin, dipyridamole, clopidogrel, ticlopidine, cilostazol.
In some embodiments, the mass ratio of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, to the other active agent in the medicament is from 0.1 to 99.9:0.1 to 99.9.
In some embodiments, the mass percentage of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the medicament is between 0.1 and 99.9%.
In some embodiments, the diabetic complication is a stage i, ii, iii, or iv diabetic complication.
In some embodiments, the diabetic complication is selected from the group consisting of: diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic cataract, diabetic bladder disease, diabetic keratopathy, diabetic dermatological lesions, diabetic microangiopathy, diabetic peripheral neuropathy, diabetic co-hyperlipidemia, myocardial infarction, macular edema, impaired nerve conduction, diabetic wounds.
In some embodiments, the drug is an orally administered agent, an injectable agent, an implantable agent, a spray administered agent, or an inhaled agent.
In some embodiments, the dosage form of the medicament includes, but is not limited to, injection, tablet, granule, capsule, drop pill, sustained release formulation, oral liquid formulation, powder or gel.
In some embodiments, the medicament further comprises a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
In a third aspect of the invention, there is provided a pharmaceutical composition comprising daphnetin, or a pharmaceutically acceptable salt or solvate thereof, and a further active drug; the other active agents include at least one selected from the group consisting of: biguanides, insulin; angiotensin converting enzyme inhibitor, angiotensin receptor antagonist, statin, anti-platelet aggregation drug, prostaglandin E2, pentoxifylline, anisodamine, methyl vitamin B12, neurotrophic factor, C peptide, a-lipoic acid, tongxin capsule, ginseng radix Rubri Cordyceps capsule, and Ginkgoatamol.
In some embodiments, the biguanide drug comprises metformin.
In some embodiments, the angiotensin converting enzyme inhibitor comprises at least one selected from the group consisting of: captopril, enalapril, perindopril, benazepril, imidapril, fosinopril.
In some embodiments, the angiotensin receptor antagonist comprises at least one selected from the group consisting of: valsartan, irbesartan, losartan, candesartan, telmisartan, olmesartan.
In some embodiments, the statin comprises at least one selected from the group consisting of: atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, mevastatin.
In some embodiments, the anti-platelet aggregation drug comprises at least one selected from the group consisting of: aspirin, dipyridamole, clopidogrel, ticlopidine, cilostazol.
In some embodiments, the mass ratio of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, to the other active agent in the pharmaceutical composition is from 0.1 to 99.9:0.1 to 99.9.
In some embodiments, the mass percentage of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the pharmaceutical composition is between 0.1 and 99.9%.
In some embodiments, the pharmaceutical composition is an orally administered agent, an injectable agent, an implantable agent, a spray administered agent, or an inhaled agent.
In some embodiments, the dosage form of the pharmaceutical composition includes, but is not limited to, injection, tablet, granule, capsule, drop pill, sustained release formulation, oral liquid formulation, powder or gel.
In some embodiments, the pharmaceutical composition further comprises a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
In a fourth aspect, the invention provides a method for preparing a pharmaceutical composition according to the third aspect of the invention, comprising mixing daphnetin or a pharmaceutically acceptable salt or solvate thereof, the other active drug and an optional drug carrier or pharmaceutically acceptable auxiliary material uniformly.
In a fifth aspect of the invention, there is provided a method of treatment of a diabetic complication comprising administering to a subject an effective amount of a medicament comprising daphnetin, or a pharmaceutically acceptable salt or solvate thereof.
In some embodiments, the medicament further comprises an additional active medicament; the other active agents include at least one selected from the group consisting of: biguanides, insulin; angiotensin converting enzyme inhibitor, angiotensin receptor antagonist, statin, anti-platelet aggregation drug, prostaglandin E2, pentoxifylline, anisodamine, methyl vitamin B12, neurotrophic factor, C peptide, a-lipoic acid, tongxin capsule, ginseng radix Rubri Cordyceps capsule, and Ginkgoatamol.
In some embodiments, the biguanide drug comprises metformin.
In some embodiments, the angiotensin converting enzyme inhibitor comprises at least one selected from the group consisting of: captopril, enalapril, perindopril, benazepril, imidapril, fosinopril.
In some embodiments, the angiotensin receptor antagonist comprises at least one selected from the group consisting of: valsartan, irbesartan, losartan, candesartan, telmisartan, olmesartan.
In some embodiments, the statin comprises at least one selected from the group consisting of: atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, mevastatin.
In some embodiments, the anti-platelet aggregation drug comprises at least one selected from the group consisting of: aspirin, dipyridamole, clopidogrel, ticlopidine, cilostazol.
In some embodiments, the subject comprises a mammal; such as humans, rabbits, pigs, sheep, cattle, rats, mice, monkeys, etc.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects:
(1) The invention provides the application of daphnetin in preparing the medicine for treating diabetes complications, which not only expands the application range of daphnetin, but also provides a new alternative scheme for treating diabetes complications.
(2) The invention provides an application of daphnetin and a plurality of other active medicaments in combination in preparing medicaments for treating diabetic complications, and the combination has a synergistic effect in treating the diabetic complications, so that the treatment effect can be remarkably improved.
(3) The invention provides a pharmaceutical composition for treating diabetic complications, which has good effect in the aspect of treating diabetic complications, and each component in the pharmaceutical composition is a known medicine which can be used for clinic, so that the safety is high.
Detailed Description
Exemplary embodiments of the present disclosure will be described in detail below. It should be understood that the present disclosure may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art.
The "range" disclosed herein is defined in terms of lower and upper limits, with the given range being defined by the selection of a lower and an upper limit, the selected lower and upper limits defining the boundaries of the particular range. Ranges that are defined in this way can be inclusive or exclusive of the endpoints, and any combination can be made, i.e., any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60 to 120 and 80 to 110 are listed for a particular parameter, it is understood that ranges of 60 to 110 and 80 to 120 are also contemplated. Furthermore, if minimum range values 1 and 2 are listed and maximum range values 3, 4, and 5 are listed, the following ranges are all contemplated: 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4 and 2 to 5. In this application, unless otherwise indicated, the numerical ranges "a-b" represent shorthand representations of any combination of real numbers between a and b, where a and b are both real numbers. For example, the numerical range "0-5" means that all real numbers between "0-5" have been listed throughout, and "0-5" is only a shorthand representation of a combination of these values. When a certain parameter is expressed as an integer of 2 or more, it is disclosed that the parameter is, for example, an integer of 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12 or the like.
All embodiments of the invention as well as alternative embodiments may be combined with each other to form new solutions unless otherwise specified.
All technical features of the invention as well as optional technical features may be combined with each other to form new technical solutions unless stated otherwise.
All steps of the invention may be performed sequentially or randomly, preferably sequentially, unless otherwise indicated. For example, the method comprises steps (a) and (b), meaning that the method may comprise steps (a) and (b) performed sequentially, or may comprise steps (b) and (a) performed sequentially. For example, it is mentioned that the method may further comprise step (c), meaning that step (c) may be added to the method in any order, e.g. the method may comprise steps (a), (b) and (c), may also comprise steps (a), (c) and (b), may also comprise steps (c), (a) and (b), etc.
Reference to "comprising" and "including" in this disclosure means open, but also closed, unless otherwise indicated. For example, the terms "comprising" and "comprises" may mean that other components not listed may be included or included, or that only listed components may be included or included.
The term "effective amount" of the present invention, unless otherwise indicated, designates an amount of a compound sufficient to produce the desired response, such as an improvement in or complete cure of diabetic complications. For therapeutic purposes, an effective amount is also an amount by which any deleterious effects of the compound are offset by a therapeutically beneficial effect. The specific effective amount or sufficient amount will vary with factors such as the particular condition being treated, the physical condition of the patient (e.g., the weight, age or sex of the patient, the type of subject being treated, the duration of the treatment). An effective amount may be expressed, for example, in grams, milligrams or micrograms or in milligrams per kilogram of body weight (mg/kg). Alternatively, the effective amount may be expressed in terms of the concentration of the active ingredient (e.g., daphnetin of the present disclosure), such as molar concentration, mass concentration, volume concentration, molar concentration, mole fraction, mass fraction, and mixing ratio. Furthermore, the person skilled in the art can calculate the human equivalent dose of a drug (e.g. a drug comprising daphnetin of the invention) based on the dose determined from the animal model.
Unless otherwise indicated, the term "treatment" includes its generally accepted meaning, which includes preventing, inhibiting, ameliorating, and slowing, halting, or reversing the progression of the symptoms or intended lesions produced. As such, the present invention encompasses both therapeutic and prophylactic administration.
The terms "subject" or "patient" are used interchangeably herein, unless otherwise indicated, to refer to a mammal that can be treated by the medicaments or pharmaceutical compositions provided herein. The term "mammal" refers to all members of the mammalian class, including humans, primates, domestic animals and farm animals, such as rabbits, pigs, sheep, cattle, and the like. "subject" or "patient" refers to both male (male) and female (female) sexes unless one sex is specifically indicated. In a preferred embodiment, the subject is a human.
The term "drug carrier" refers to a system that alters the manner and distribution of a drug into the body, controls the release rate of the drug, and delivers the drug to a targeted organ, unless otherwise indicated. The invention is not limited to the particular type of drug carrier, and in some embodiments, the drug or pharmaceutical composition provided by the invention may employ drug carriers including, but not limited to, microcapsules, microspheres, nanoparticles, and liposomes.
Unless otherwise indicated, the term "pharmaceutically acceptable adjuvant" refers to an adjuvant that, except for the active ingredient, has no significant stimulating effect on the organism and does not impair the biological activity and properties of the active ingredient. The use of pharmaceutically acceptable excipients to prepare pharmaceutical formulations is well known to those of ordinary skill in the art. In some embodiments, pharmaceutically acceptable excipients that may be employed in the medicaments or pharmaceutical compositions provided herein include, but are not limited to: propellants, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, tonicity modifiers, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integration agents, permeation promoters, pH adjusting agents, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, and release retarders.
Daphnetin (Daphnetin), also known as: daphnolide, daphnetin A, and daphnetin are effective components of daphnetin (Daphne Korean Nakai) belonging to genus daphne. The medicine is a novel medicine which is first prepared by chemical synthesis in China, the chemical name is 7, 8-dihydroxycoumarin, and the molecular formula is C 9 H 6 O 4 The chemical structure is shown as the formula (I),
in a first aspect of the invention there is provided the use of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of diabetic complications.
In some embodiments, the medicament has daphnetin, or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient. For example, daphnetin, or a pharmaceutically acceptable salt or solvate thereof, may be the sole active ingredient of the medicament, or be one of the active ingredients.
In some embodiments, the daphnetin, or a pharmaceutically acceptable salt or solvate thereof, is present in the medicament in an amount effective to treat the diabetic complication.
In some embodiments, the mass percentage of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient in the medicament is 0.1-99.9%; for example, the concentration may be about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99%, 99.5%, 99.9%, or the like.
In some embodiments, the diabetic complication is a stage i, ii, iii, or iv diabetic complication.
In some embodiments, the diabetic complication is selected from the group consisting of: diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic cataract, diabetic bladder disease, diabetic keratopathy, diabetic dermatological lesions, diabetic microangiopathy, diabetic peripheral neuropathy, diabetic co-hyperlipidemia, myocardial infarction, macular edema, impaired nerve conduction, diabetic wounds.
In some embodiments, the drug is an orally administered agent, an injectable agent, an implantable agent, a spray administered agent, or an inhaled agent.
In some embodiments, the dosage form of the medicament includes, but is not limited to, injection, tablet, granule, capsule, drop pill, sustained release formulation, oral liquid formulation, powder or gel.
In some embodiments, the medicament further comprises a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
In a second aspect of the invention, there is provided the use of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in combination with other active agents for the manufacture of a medicament for the treatment of diabetic complications; the other active agents include at least one selected from the group consisting of: biguanides, such as metformin; insulin; angiotensin Converting Enzyme Inhibitors (ACEI), such as captopril, enalapril, perindopril, benazepril, imidapril, fosinopril; angiotensin receptor Antagonists (ARBs), such as valsartan, irbesartan, losartan, candesartan, telmisartan, olmesartan; statin drugs such as atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, mevastatin; antiplatelet aggregation drugs such as aspirin, dipyridamole, clopidogrel, ticlopidine, cilostazol; prostaglandin E2; pentoxifylline; anisodamine; methyl vitamin B12; neurotrophic factors; c Peptide (C-Peptide); a-lipoic acid; capsule for dredging heart meridian; red ginseng cordyceps sinensis capsule; ginkgo dipyridamole.
In some embodiments, the mass ratio of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, to the other active agent in the medicament is 0.1-99.9:0.1-99.9; such as 1-90:0.1-90, 1-10:50-90, 10-35:40-80, 50-70:20-30, 60-90:0.1-10, 75-99:1-5, 55-80:10-30, etc.; for example, in some embodiments, the parts by weight of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the medicament may be selected from the group consisting of: 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5, 99.9, etc.;
the parts by weight of the other active agents may be selected from the group consisting of: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.9, etc.
In some embodiments, the mass percentage of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the medicament is between 0.1 and 99.9%; for example, the amount may be about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99%, 99.5%, 99.9%, or the like.
In some embodiments, the diabetic complication is a stage i, ii, iii, or iv diabetic complication.
In some embodiments, the diabetic complication is selected from the group consisting of: diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic cataract, diabetic bladder disease, diabetic keratopathy, diabetic dermatological lesions, diabetic microangiopathy, diabetic peripheral neuropathy, diabetic co-hyperlipidemia, myocardial infarction, macular edema, impaired nerve conduction, diabetic wounds.
In some embodiments, the drug is an orally administered agent, an injectable agent, an implantable agent, a spray administered agent, or an inhaled agent.
In some embodiments, the dosage form of the medicament includes, but is not limited to, injection, tablet, granule, capsule, drop pill, sustained release formulation, oral liquid formulation, powder or gel.
In some embodiments, the medicament further comprises a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
In a third aspect of the invention, there is provided a pharmaceutical composition comprising daphnetin, or a pharmaceutically acceptable salt or solvate thereof, and a further active drug; the other active agents include at least one selected from the group consisting of: biguanides, such as metformin; insulin; angiotensin Converting Enzyme Inhibitors (ACEI), such as captopril, enalapril, perindopril, benazepril, imidapril, fosinopril; angiotensin receptor Antagonists (ARBs), such as valsartan, irbesartan, losartan, candesartan, telmisartan, olmesartan; statin drugs such as atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, mevastatin; antiplatelet aggregation drugs such as aspirin, dipyridamole, clopidogrel, ticlopidine, cilostazol; prostaglandin E2; pentoxifylline; anisodamine; methyl vitamin B12; neurotrophic factors; c Peptide (C-Peptide); a-lipoic acid; capsule for dredging heart meridian; red ginseng cordyceps sinensis capsule; ginkgo dipyridamole.
In some embodiments, the mass ratio of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, to the other active agent in the pharmaceutical composition is from 0.1 to 99.9:0.1 to 99.9; such as 1-90:1-90, 1-10:50-90, 10-35:40-80, 50-70:20-30, 60-90:0.1-10, 75-99:1-5, 55-80:10-30, etc.; for example, in some embodiments, the parts by weight of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the medicament may be selected from the group consisting of: 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5, 99.9, etc.;
the parts by weight of the other active agents may be selected from the group consisting of: 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.9, etc.
In some embodiments, the mass percentage of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the pharmaceutical composition is between 0.1 and 99.9%; for example, the amount may be about 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 99%, 99.5%, 99.9%, or the like.
In some embodiments, the pharmaceutical composition is an orally administered agent, an injectable agent, an implantable agent, a spray administered agent, or an inhaled agent.
In some embodiments, the dosage form of the pharmaceutical composition includes, but is not limited to, injection, tablet, granule, capsule, drop pill, sustained release formulation, oral liquid formulation, powder or gel.
In some embodiments, the pharmaceutical composition further comprises a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
The present invention is not limited to the above-mentioned embodiments, and any changes or substitutions that can be easily understood by those skilled in the art within the technical scope of the present invention are intended to be included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims (10)

1. The application of daphnetin or pharmaceutically acceptable salt or solvate thereof in preparing medicines for treating diabetic complications.
2. The use according to claim 1, wherein the medicament comprises daphnetin or a pharmaceutically acceptable salt or solvate thereof as an active ingredient;
preferably, the daphnetin, or a pharmaceutically acceptable salt or solvate thereof, is present in the medicament in an amount effective to treat the diabetic complication;
preferably, the content of daphnetin or pharmaceutically acceptable salts or solvates thereof as active ingredient in the medicament is 0.1-99.9% (w/w).
3. The use according to claim 1, wherein the diabetic complication is a stage i, ii, iii or iv diabetic complication;
preferably, the diabetic complication is selected from the group consisting of: diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic cataract, diabetic bladder disease, diabetic keratopathy, diabetic dermatological lesions, diabetic microangiopathy, diabetic peripheral neuropathy, diabetic co-hyperlipidemia, myocardial infarction, macular edema, impaired nerve conduction, diabetic wounds.
4. The daphnetin or pharmaceutically acceptable salts or solvates thereof and other active medicaments are used in combination for preparing medicaments for treating diabetic complications; the other active agents include at least one selected from the group consisting of: biguanides, insulin; angiotensin converting enzyme inhibitor, angiotensin receptor antagonist, statin, anti-platelet aggregation drug, prostaglandin E2, pentoxifylline, anisodamine, methyl vitamin B12, neurotrophic factor, C peptide, a-lipoic acid, tongxin capsule, ginseng radix Rubri Cordyceps capsule, and Ginkgoatamol.
5. The use according to claim 4, wherein the biguanide drug comprises metformin;
preferably, the angiotensin converting enzyme inhibitor comprises at least one selected from the group consisting of: captopril, enalapril, perindopril, benazepril, imidapril, fosinopril;
preferably, the angiotensin receptor antagonist comprises at least one selected from the group consisting of: valsartan, irbesartan, losartan, candesartan, telmisartan, olmesartan;
preferably, the statin comprises at least one selected from the group consisting of: atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, mevastatin;
preferably, the anti-platelet aggregation drug comprises at least one selected from the group consisting of: aspirin, dipyridamole, clopidogrel, ticlopidine, cilostazol;
preferably, in the medicament, the mass ratio of daphnetin or pharmaceutically acceptable salt or solvate thereof to the other active medicament is 0.1-99.9:0.1-99.9;
preferably, in the medicament, the mass percentage of daphnetin or pharmaceutically acceptable salt or solvate thereof is 0.1-99.9%.
6. The use according to claim 4 or 5, wherein the medicament is an orally administered medicament, an injectable medicament, an implantable medicament, a spray administered medicament or an inhaled medicament;
preferably, the dosage forms of the medicine comprise, but are not limited to, injection, tablet, granule, capsule, dripping pill, sustained release agent, oral liquid preparation, powder or gel;
preferably, the medicament further comprises a pharmaceutical carrier or pharmaceutically acceptable excipients.
7. A pharmaceutical composition comprising daphnetin, or a pharmaceutically acceptable salt or solvate thereof, and an additional active agent; the other active agents include at least one selected from the group consisting of: biguanides, insulin; angiotensin converting enzyme inhibitor, angiotensin receptor antagonist, statin, anti-platelet aggregation drug, prostaglandin E2, pentoxifylline, anisodamine, methyl vitamin B12, neurotrophic factor, C peptide, a-lipoic acid, tongxin capsule, ginseng radix Rubri Cordyceps capsule, and Ginkgoatamol.
8. The pharmaceutical composition of claim 7, wherein the biguanide drug comprises metformin;
preferably, the angiotensin converting enzyme inhibitor comprises at least one selected from the group consisting of: captopril, enalapril, perindopril, benazepril, imidapril, fosinopril;
preferably, the angiotensin receptor antagonist comprises at least one selected from the group consisting of: valsartan, irbesartan, losartan, candesartan, telmisartan, olmesartan;
preferably, the statin comprises at least one selected from the group consisting of: atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, mevastatin;
preferably, the anti-platelet aggregation drug comprises at least one selected from the group consisting of: aspirin, dipyridamole, clopidogrel, ticlopidine, cilostazol;
preferably, the mass ratio of daphnetin or a pharmaceutically acceptable salt or solvate thereof and the other active drug in the pharmaceutical composition is 0.1-99.9:0.1-99.9;
preferably, the mass percentage of daphnetin or pharmaceutically acceptable salt or solvate thereof in the pharmaceutical composition is 0.1-99.9%.
9. The pharmaceutical composition of claim 7 or 8, wherein the pharmaceutical composition is an orally administered agent, an injectable agent, an implantable agent, a spray administered agent, or an inhaled agent;
preferably, the dosage form of the pharmaceutical composition comprises, but is not limited to, injection, tablet, granule, capsule, dripping pill, sustained release agent, oral liquid preparation, powder or gel;
preferably, the pharmaceutical composition further comprises a pharmaceutical carrier or pharmaceutically acceptable excipients.
10. A method of preparing a pharmaceutical composition according to any one of claims 7 to 9, comprising mixing daphnetin or a pharmaceutically acceptable salt or solvate thereof, said other active agent and optionally a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
CN202311158734.8A 2023-09-08 2023-09-08 Application of daphnetin and combination containing daphnetin in preparation of diabetes complication medicaments Pending CN117243947A (en)

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