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CN117243948A - Application of daphnetin-containing composition in preparation of rheumatic arthritis drugs - Google Patents

Application of daphnetin-containing composition in preparation of rheumatic arthritis drugs Download PDF

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Publication number
CN117243948A
CN117243948A CN202311158735.2A CN202311158735A CN117243948A CN 117243948 A CN117243948 A CN 117243948A CN 202311158735 A CN202311158735 A CN 202311158735A CN 117243948 A CN117243948 A CN 117243948A
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Prior art keywords
daphnetin
pharmaceutically acceptable
pharmaceutical composition
agent
solvate
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Chinese (zh)
Inventor
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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Priority to CN202311158735.2A priority Critical patent/CN117243948A/en
Publication of CN117243948A publication Critical patent/CN117243948A/en
Pending legal-status Critical Current

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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
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Rheumatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to an application of a daphnetin-containing composition in preparation of a medicament for treating rheumatic arthritis, when daphnetin or pharmaceutically acceptable salt or solvate thereof is combined with a plurality of other active medicaments such as diclofenac sodium, ibuprofen, glucocorticoid, iguratimod and the like, the daphnetin-containing composition is used for preparing the medicament for treating the rheumatic arthritis, the daphnetin-containing composition can play a role in synergy in treating the rheumatic arthritis, and the curative effect on the rheumatic arthritis is remarkably improved.

Description

Application of daphnetin-containing composition in preparation of rheumatic arthritis drugs
Technical Field
The invention relates to the technical field of medicines, in particular to application of a daphnetin-containing composition in preparation of a medicine for treating rheumatic arthritis.
Background
Rheumatic arthritis (rheumatic arthritis, RA) is one of the main manifestations of rheumatic fever, most of which is caused by acute fever and arthralgia, and typical manifestations are mild or moderate fever, wandering polyarthritis, the affected joints are large joints such as knee, ankle, shoulder, elbow, wrist and the like, the affected joints are often transferred from one joint to another, the lesions are locally red, swelling, burning and severe pain, some patients also have the diseases of several joints at the same time, atypical patients only have arthralgia without other inflammation manifestations, the acute inflammation generally subsides for 2-4 weeks without sequelae, but recurrent attacks often. If the rheumatic activity affects the heart, rheumatic heart disease can occur, even leaving behind heart valve lesions.
The therapeutic drugs for treating the rheumatoid arthritis which are commonly used clinically mainly comprise: non-steroidal anti-inflammatory drugs (NSAIDS), anti-rheumatic drugs (DMARDs) for improving the condition, glucocorticoids, etc., but the therapeutic effect is not ideal, and it is difficult to effectively inhibit the progression of rheumatic arthritis diseases. Therefore, research based on the treatment of rheumatoid arthritis remains a problem to be solved in the pharmaceutical community.
Disclosure of Invention
The invention aims to provide application of a composition containing daphnetin in preparation of a medicament for treating rheumatic arthritis.
To this end, in a first aspect, the present invention provides 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 rheumatoid arthritis; the other active agents include at least one selected from the group consisting of: diclofenac sodium, ibuprofen, glucocorticoid, iguratimod.
In some embodiments, the glucocorticoid comprises at least one selected from the group consisting of: prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
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 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 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: diclofenac sodium, ibuprofen, glucocorticoid, iguratimod.
In some embodiments, the glucocorticoid comprises at least one selected from the group consisting of: prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
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 third aspect of the present invention, there is provided a method of preparing a pharmaceutical composition according to the second aspect of the present invention, comprising mixing daphnetin or a pharmaceutically acceptable salt or solvate thereof, said other active agent, and optionally a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
In a fourth aspect of the invention, there is provided a method of treatment of rheumatoid arthritis 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: diclofenac sodium, ibuprofen, glucocorticoid, iguratimod.
In some embodiments, the glucocorticoid comprises at least one selected from the group consisting of: prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
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 application of daphnetin and a plurality of other active medicaments in combination in preparation of medicaments for treating rheumatic arthritis, and the combination has a synergistic effect in treating the rheumatic arthritis, so that the treatment effect can be remarkably improved.
(2) The invention provides a pharmaceutical composition for treating rheumatic arthritis, which has good effect on the aspect of treating the rheumatic arthritis, and all components in the medicine are known medicines which can be used for clinic, so that the safety is higher.
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 or complete cure of rheumatoid arthritis. 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 combination with other active agents in the manufacture of a medicament for the treatment of rheumatoid arthritis; the other active agents include at least one selected from the group consisting of: diclofenac sodium, ibuprofen, glucocorticoid, iguratimod.
In some embodiments, the glucocorticoid comprises at least one selected from the group consisting of: prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
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 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 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: diclofenac sodium, ibuprofen, glucocorticoid, iguratimod.
In some embodiments, the glucocorticoid comprises at least one selected from the group consisting of: prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
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 daphnetin or pharmaceutically acceptable salt or solvate thereof and other active medicaments are used in combination for preparing medicaments for treating rheumatic arthritis; the other active agents include at least one selected from the group consisting of: diclofenac sodium, ibuprofen, glucocorticoid, iguratimod.
2. The use according to claim 1, wherein 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.
3. The use according to claim 1, wherein the mass percentage of daphnetin or a pharmaceutically acceptable salt or solvate thereof in the medicament is between 0.1 and 99.9%.
4. A use according to any one of claims 1 to 3 wherein the medicament is an orally administered, an injectable, an implantable, a spray or an inhaled medicament;
preferably, the dosage form of the medicament is selected from the group consisting of: injection, tablet, granule, capsule, dripping pill, delayed release agent, oral liquid, powder, and gel.
5. A use according to any one of claims 1 to 3 wherein the medicament further comprises a pharmaceutical carrier or pharmaceutically acceptable adjuvant.
6. 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: diclofenac sodium, ibuprofen, glucocorticoid, iguratimod.
7. The pharmaceutical composition according to claim 6, wherein the mass ratio of daphnetin or a pharmaceutically acceptable salt or solvate thereof and the other active agent in the pharmaceutical composition is between 0.1 and 99.9:0.1 and 99.9.
8. The pharmaceutical composition of claim 6, wherein the mass percentage of daphnetin, or a pharmaceutically acceptable salt or solvate thereof, in the pharmaceutical composition is between 0.1 and 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 is selected from the group consisting of: injection, tablet, granule, capsule, dripping pill, delayed release agent, oral liquid, powder, and gel;
preferably, the pharmaceutical composition further comprises a pharmaceutical carrier or pharmaceutically acceptable excipients.
10. The method of preparing a pharmaceutical composition according to any one of claims 6 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 excipients uniformly.
CN202311158735.2A 2023-09-08 2023-09-08 Application of daphnetin-containing composition in preparation of rheumatic arthritis drugs Pending CN117243948A (en)

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CN202311158735.2A CN117243948A (en) 2023-09-08 2023-09-08 Application of daphnetin-containing composition in preparation of rheumatic arthritis drugs

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