[go: up one dir, main page]

CN115252626A - Pharmaceutical composition containing glucocorticoid and application thereof - Google Patents

Pharmaceutical composition containing glucocorticoid and application thereof Download PDF

Info

Publication number
CN115252626A
CN115252626A CN202210992088.4A CN202210992088A CN115252626A CN 115252626 A CN115252626 A CN 115252626A CN 202210992088 A CN202210992088 A CN 202210992088A CN 115252626 A CN115252626 A CN 115252626A
Authority
CN
China
Prior art keywords
pharmaceutical composition
triptolide
poloxamer
gel
glucocorticoid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202210992088.4A
Other languages
Chinese (zh)
Other versions
CN115252626B (en
Inventor
常倩
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Taizhou Hospital Of Traditional Chinese Medicine
Original Assignee
Taizhou Hospital Of Traditional Chinese Medicine
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taizhou Hospital Of Traditional Chinese Medicine filed Critical Taizhou Hospital Of Traditional Chinese Medicine
Priority to CN202210992088.4A priority Critical patent/CN115252626B/en
Publication of CN115252626A publication Critical patent/CN115252626A/en
Application granted granted Critical
Publication of CN115252626B publication Critical patent/CN115252626B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators

Landscapes

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

Abstract

The invention relates to a pharmaceutical composition for treating rheumatoid arthritis, wherein the weight ratio of active ingredients, namely glucocorticoid to a tripterygium wilfordii natural product is 1: (1-5), the glucocorticoid is methylprednisolone or methylprednisolone aceponate, and the natural product of tripterygium wilfordii is selected from one or more of triptolide, tripdiolide and triptolide. The pharmaceutical composition provided by the invention has the advantages of simple preparation method and stable quality, and various active ingredients can be used for synergistic treatment of rheumatoid arthritis while exerting respective effects.

Description

Pharmaceutical composition containing glucocorticoid and application thereof
Technical Field
The invention relates to the field of medicines, and particularly relates to a pharmaceutical composition containing glucocorticoid.
Background
Rheumatoid arthritis is a chronic autoimmune disease characterized by destructive and symmetrical joint lesions and arthromeningitis, and mainly comprises symptoms such as joint deformity, morning stiffness, hand, foot, wrist, ankle, temporomandibular arthritis and the like, which not only can reduce the motion function of a patient, but also can accumulate systems such as respiration, kidney, heart and the like, so that the life and the work of the patient are seriously influenced. If the condition of the patient cannot be effectively controlled in time, complications such as sicca syndrome, pericarditis, anemia and necrotizing vasculitis can be caused, and the life safety of the patient is threatened.
At present, the pathogenesis of rheumatoid arthritis in the medical field is still in a research stage, but researchers think that heredity and environment are main factors for triggering rheumatoid arthritis, and meanwhile, synovial tissues and synovial fluids of patients have more immune cells, immune molecules and other substances, which indicates that the occurrence of rheumatoid arthritis may be related to the activation or release of the substances or accelerate the progress of the disease of the patients under the action of the substances.
Methylprednisolone is a synthetic halogen-free intermediate-acting glucocorticoid, the structural characteristics of unsaturated double bonds of which increase the lipid solubility of the glucocorticoid and enable the glucocorticoid to easily penetrate a lipid barrier to quickly reach a target organ, so the methylprednisolone has the advantages of quick response, better tissue penetrability, long biological half-life period, long action time, low protein binding rate, large distribution volume, strong anti-inflammatory action, weak action of mineralocorticoid, small influence on sodium hydrate storage and weak inhibition effect on HPA axis.
Methylprednisolone aceponate is a glucocorticoid medicine of the fourth generation developed by Schering AG company in Germany, with the trade name Advantan, marketed in 1992 in Germany, and subsequently marketed in more than ten countries such as Italy, korea, etc. Methylprednisolone aceponate is white or off-white crystalline powder in appearance, is very soluble in dichloromethane, is soluble in methanol, ethanol and acetone, and is almost insoluble in water. Compared with prednisolone, the restructured methylprednisolone aceponate introduces propionate and acetate groups, so that the lipophilicity of the methylprednisolone aceponate is greatly improved, the drug molecules can rapidly and effectively penetrate through the horny layer to reach effective concentration at a treatment part, and the methylprednisolone aceponate is ensured not to reach high concentration in blood, so that the side effects of the whole body are reduced.
Tripterygium wilfordii, as a traditional Chinese medicine, is bitter in taste and has the effects of promoting blood circulation to remove blood stasis, clearing heat and removing toxicity, relieving swelling and resolving masses, killing parasites to stop bleeding and the like. The roots, stems and leaves of the tripterygium wilfordii can be used as medicines, but the main clinical medicine part at present is the roots. Pharmacological and clinical researches prove that more than 200 monomeric compounds can be separated from the tripterygium wilfordii, wherein the tripterygium wilfordii polyglycoside is the main effective component of the tripterygium wilfordii. Tripterygium wilfordii has anti-inflammatory, anti-tumor, immunoregulation and anti-fertility properties, and is widely used for treating various autoimmune diseases such as rheumatoid arthritis, glomerulonephritis and lupus erythematosus.
At present, no report is found in documents of combination of glucocorticoid and tripterygium wilfordii natural products for treating rheumatoid arthritis.
Disclosure of Invention
The invention aims to solve the technical problem of providing a pharmaceutical composition which can effectively treat rheumatoid arthritis and has natural main active ingredient sources.
The technical scheme adopted by the invention for solving the problems is to provide a pharmaceutical composition for treating rheumatoid arthritis, wherein the weight ratio of active ingredients, namely glucocorticoid to a tripterygium wilfordii natural product is 1: (1-5).
Preferably, the glucocorticoid is methylprednisolone or methylprednisolone aceponate. More preferably, the glucocorticoid is methylprednisolone aceponate.
Preferably, the tripterygium wilfordii natural product is selected from one or more of triptolide, tripdiolide and triptolide. More preferably, the natural product of tripterygium wilfordii is selected from one or more of triptolide and triptolide. Most preferably, the natural product of tripterygium wilfordii is a composition of triptolide and triptolide.
Preferably, in the pharmaceutical composition, the weight ratio of methylprednisolone aceponate, triptolide and triptolide A is 1: (1-2): (1-2).
Preferably, in the pharmaceutical composition, the weight ratio of methylprednisolone aceponate, triptolide and triptolide A is 1:2:2.
preferably, the pharmaceutical composition further comprises pharmaceutically acceptable auxiliary materials.
Preferably, the pharmaceutical composition is an external preparation.
Preferably, the pharmaceutical composition is a patch, a film, an ointment or a gel. More preferably, the pharmaceutical composition is a gel.
Preferably, the gel comprises a gel matrix, a humectant, a solubilizer and a solvent.
Preferably, the gel matrix is poloxamer 407 and/or poloxamer 188; more preferably, the gel matrix is a composition of poloxamer 407 and poloxamer 188, and the weight ratio of poloxamer 407 to poloxamer 188 is (1-5): 1; most preferably, the gel matrix is a combination of poloxamer 407 and poloxamer 188 in a weight ratio of 3.
Preferably, the humectant is glycerol, the solubilizer is tween 80, and the solvent is distilled water.
Preferably, the gel comprises poloxamer 407, poloxamer 188, glycerol, tween 80 and distilled water.
More preferably, the gel is prepared from the following components in percentage by weight: 0.2% methylprednisolone aceponate, 0.4% triptolide, 9% poloxamer 407, 3% poloxamer 188, 14% glycerol, 3% tween 80 and 70% distilled water.
The second aspect of the present invention provides a method for preparing the above pharmaceutical composition, comprising the steps of:
(1) Mixing glucocorticoid, radix Tripterygii Wilfordii natural product and solubilizer to obtain medicinal liquid;
(2) Adding a humectant into the gel matrix, uniformly mixing, and uniformly mixing with the liquid medicine prepared in the step (1);
(3) And (3) adding a solvent into the solution obtained in the step (2), stirring for swelling, and standing for 24 hours to obtain the nano-composite material.
The third aspect of the invention also provides the application of the pharmaceutical composition in preparing a medicament for treating rheumatoid arthritis.
The fourth aspect of the invention also provides the application of the pharmaceutical composition in preparing a medicament for reducing the content of one or more of TNF-alpha, IL-1 beta and INF-gamma in serum.
Preferably, the invention also provides the application of the pharmaceutical composition in preparing a medicament for simultaneously reducing the contents of TNF-alpha, IL-1 beta and INF-gamma in serum.
The fifth aspect of the invention also provides application of a gel matrix in improving the chemical stability of the natural product of tripterygium wilfordii in the pharmaceutical composition, wherein the gel matrix is a composition of poloxamer 407 and poloxamer 188.
Preferably, the gel matrix is prepared from (1-5) by weight: 1 poloxamer 407 and poloxamer 188; more preferably, the gel matrix is a composition of poloxamer 407 and poloxamer 188 in a weight ratio of 3.
Preferably, the invention also provides application of a gel matrix in simultaneously improving the chemical stability of the triptolide and the triptolide in the pharmaceutical composition, wherein the gel matrix is a composition of poloxamer 407 and poloxamer 188 with the weight ratio of 3.
The invention has the advantages that:
the inventor of the invention unexpectedly finds that the combined use of the glucocorticoid methylprednisolone aceponate and a natural product of tripterygium wilfordii selected from triptolide, triptolide and triptolide has unexpected excellent effect on treating the rheumatoid arthritis, and various active ingredients can synergistically treat the rheumatoid arthritis while exerting respective effects. In addition, the gel preparation with obviously improved chemical stability of the natural products of the tripterygium wilfordii is obtained by preferably selecting the types of the gel matrixes (poloxamer 407 and poloxamer 188), and is favorable for quality control and long-term storage of the pharmaceutical preparation.
Detailed Description
The present invention will be further described with reference to the following examples, but the embodiments of the present invention are not limited thereto. The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Example 1 gel preparation F1 containing Methylprednisolone aceponate
Mixing 0.2g methylprednisolone aceponate, 0.4g triptolide and 0.4g triptolide A with 3g tween 80 to obtain medicinal liquid; adding 14g of glycerol into a mixture of 9g of poloxamer 407 and 3g of poloxamer 188, uniformly mixing, and uniformly mixing with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation F1.
Example 2 Methylprednisolone aceponate-containing gel formulation F2
Mixing 0.2g methylprednisolone aceponate, 0.2g triptolide and 0.6g triptolide A with 3g tween 80 to obtain medicinal liquid; adding 14g of glycerol into the mixture of 9g of poloxamer 407 and 3g of poloxamer 188, mixing uniformly, and mixing uniformly with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation F2.
Example 3 gel formulation containing methylprednisolone aceponate F3
Mixing 0.2g methylprednisolone aceponate, 0.6g triptolide, 0.2g triptolide A and 3g Tween 80 to obtain medicinal liquid; adding 14g of glycerol into the mixture of 9g of poloxamer 407 and 3g of poloxamer 188, mixing uniformly, and mixing uniformly with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation F3.
Example 4 gel formulation containing methylprednisolone aceponate F4
Mixing 0.2g methylprednisolone aceponate, 0.4g triptolide and 0.4g triptolide A with 3g tween 80 to obtain medicinal liquid; adding 14g of glycerol into the mixture of 6g of poloxamer 407 and 6g of poloxamer 188, mixing uniformly, and mixing uniformly with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation F4.
Example 5 gel formulation containing Methylprednisolone aceponate F5
Mixing 0.2g methylprednisolone aceponate, 0.4g triptolide and 0.4g triptolide A with 3g tween 80 to obtain medicinal liquid; adding 14g of glycerol into the mixture of 11g of poloxamer 407 and 1g of poloxamer 188, mixing uniformly, and mixing uniformly with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation F5.
Example 6 gel formulation containing Methylprednisolone aceponate F6
Mixing 0.2g methylprednisolone aceponate, 0.4g triptolide and 3g Tween 80 to obtain medicinal liquid; adding 14g of glycerol into a mixture of 9g of poloxamer 407 and 3g of poloxamer 188, uniformly mixing, and uniformly mixing with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation F6.
Comparative example 1 gel preparation C1 containing Methylprednisolone Acetoacetate
Mixing 0.2g methylprednisolone aceponate, 0.8g triptolide and 3g tween-80 uniformly to obtain a liquid medicine; adding 14g of glycerol into a mixture of 9g of poloxamer 407 and 3g of poloxamer 188, uniformly mixing, and uniformly mixing with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation C1.
Comparative example 2 gel preparation C2 containing Methylprednisolone Acetoacetate
Mixing 0.2g methylprednisolone aceponate, 0.8g triptolide and 3g tween 80 uniformly to obtain a liquid medicine; adding 14g of glycerol into a mixture of 9g of poloxamer 407 and 3g of poloxamer 188, uniformly mixing, and uniformly mixing with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation C2.
Comparative example 3 gel preparation C3 containing Methylprednisolone Acetoacetate
Mixing 0.2g methylprednisolone aceponate, 0.8g triptolide A and 3g Tween 80 to obtain medicinal liquid; adding 14g of glycerol into the mixture of 9g of poloxamer 407 and 3g of poloxamer 188, mixing uniformly, and mixing uniformly with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain a gel preparation C3.
Comparative example 4 gel preparation C4 containing Methylprednisolone aceponate
Mixing 0.2g methylprednisolone aceponate, 0.4g triptolide and 0.4g triptolide A with 3g tween 80 to obtain medicinal liquid; adding 14g of glycerol into 12g of poloxamer 407, uniformly mixing, and uniformly mixing with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain a gel preparation C4.
Comparative example 5 gel preparation C5 containing Methylprednisolone aceponate
Mixing 0.2g methylprednisolone aceponate, 0.4g triptolide and 0.4g triptolide A with 3g tween 80 to obtain medicinal liquid; adding 14g of glycerol into 12g of poloxamer 188, uniformly mixing, and uniformly mixing with the liquid medicine; and continuously adding 70g of distilled water, stirring for swelling, and standing for 24 hours to obtain the gel preparation C5.
Test example 1 therapeutic effects of the pharmaceutical composition of the present invention on Rheumatoid Arthritis (RA) model rats
1. Test method
The RA rat model was established using Freund's Complete Adjuvant (FCA) induction, in particular: the left hind plantar region was injected with 0.1mL of complete freund's adjuvant, and on day 1 of injection, rat body weight and left hind sole volume were recorded, followed by measuring the volume of the non-injected sole with a plethysmograph. Re-weighed at day 21 and observed and graded according to score for secondary connective tissue severe swelling, scoring 1. (3) Tail: counting 0 point without knots; with a summary, count 1 point. (4) Front claw: the inflammation of no joint appears, and the score is 0; at least one joint presents with an inflammatory manifestation, which counts 1 point. (5) A rear claw: no inflammation appeared in joints, and the score is 0; the joints showed mild inflammation, counted 1 point; moderate inflammation, 2 points; severe inflammation, 3 points. When the secondary reaction reaches the peak value, evaluating each group of rats according to the grading method, carrying out comparative analysis on the grading result by adopting double-sample variance t test, and when the grading of each part of the rats shows obvious difference, indicating that the modeling is successful. 80 rats successfully modeled were randomly selected and divided into 8 groups, i.e., 10 rats each, of the model group, the inventive examples 1-3, 6 groups, and the comparative examples 1-3 groups. Another 10 unmolded rats were used as a blank group.
On day 2 after successful molding, the gel formulations prepared in examples 1 to 3 and 6 and comparative examples 1 to 3 were applied to the molding site at a dose of 0.1g/kg body weight 2 times a day for 4 weeks in the morning and evening on the 2 nd day after successful molding, and the gel blanks containing no active ingredient were applied to the model groups at each time (the formulation of the gel blanks was the same as that of example 1). On the 2 nd day after the drug treatment period, 5mL of tail venous blood of rats in each test group was collected by an anticoagulation tube, 3500r/min was centrifuged for 15min, and serum was separated. ELISA method for measuring contents of TNF-alpha, IL-1 beta and INF-gamma in rat serum
2. Test results
The effects of TNF-alpha, IL-1 beta and INF-gamma in the serum of the rat of the RA model by each test group are shown in the following table 1.
TABLE 1 therapeutic effect of the pharmaceutical composition of the present invention on RA model rats
Group of TNF-α(ng/L) IL-1β(ng/L) INF-γ(ng/L)
Blank group 21.38±2.56 8.51±1.34 212.36±25.41
Model set 82.04±6.14 62.92±5.20 551.91±48.09
Example 1 23.97±3.39 10.04±1.51 246.31±29.80
Example 2 36.28±3.45 19.13±2.36 329.41±35.82
Example 3 40.92±3.28 22.54±3.08 342.19±32.05
Example 6 50.29±4.07 32.09±3.37 387.62±41.26
Comparative example 1 63.26±5.50 48.05±4.16 436.19±43.81
Comparative example 2 60.07±4.48 49.74±5.87 451.28±47.25
Comparative example 3 58.25±4.96 50.01±5.51 430.92±45.74
It has been reported that IL-1 beta and TNF-alpha play a more direct role in persistent cell infiltration and induced tissue destruction at the site of joint inflammation in patients with rheumatoid arthritis, and are considered to be the main inflammatory cytokines responsible for bone resorption, destruction and articular cartilage damage, among which IL-1 beta plays a more intimate role. Therefore, blocking IL-1 beta, TNF-alpha and IFN-gamma inflammatory factors is critical to control joint damage and is a good therapeutic target for rheumatoid arthritis.
The test results in table 1 above show that the levels of TNF- α, IL-1 β and INF- γ in the serum of RA model rats treated with the gel preparations of examples 1-3 and 6 of the present invention are significantly less than those in the model group (significantly different from those in the model group), suggesting that the pharmaceutical composition of the present invention can be used for treating rheumatoid arthritis, and the mechanism of action thereof is related to the reduction of the levels of inflammatory factors TNF- α, IL-1 β and IFN- γ. In addition, the therapeutic effects of the above examples are also superior to those of comparative examples 1 to 3, confirming that the combination of three active ingredients of the present invention is significantly superior to the combination of two active ingredients in terms of treating rheumatoid arthritis on the basis of the unchanged total amount of the active ingredients, indicating that the three active ingredients produce synergistic effects, producing excellent effects which are difficult to expect.
Test example 2 study on chemical stability of the pharmaceutical composition of the present invention
1. Test method
The present experiment set 5 test groups, in which test groups 1 to 3 used the methylprednisolone aceponate-containing gel formulations of the present invention prepared in examples 1 and 4 to 5, respectively, and test groups 4 to 5 used the methylprednisolone aceponate-containing gel formulations prepared in comparative examples 4 to 5, and 3 samples were repeated for each test group. Storing the 5 test groups at 40 deg.C and 75% RH for 6 months, taking out, measuring the contents of triptolide and triptolide in the preparations of each test group, and calculating the average value of the contents of triptolide and triptolide after standing.
2. Test results
The average values of the contents of triptolide and triptolide in the test groups are shown in the following table 2.
TABLE 2 pharmaceutical compositions of the invention having tripdiolide and triptolide contents at high temperature/high humidity
Test group Content of Tripterygium wilfordii B (%) Triptolide A content (%)
Test group 1 97.66％ 98.23％
Test group 2 95.29％ 95.32％
Test group 3 95.81％ 95.01％
Test group 4 91.50％ 91.33％
Test group 5 91.07％ 90.28％
As can be seen from the data of the content of active ingredients in the above table, the gel formulations of test groups 1-3 (examples 1 and 4-5) had no significant decrease in the contents of both triptolide and triptolide after storage at high temperature and high humidity, and the content of active ingredients was kept above 95%. In contrast, in test 4 (comparative example 4) poloxamer 188 was omitted, in test 5 (comparative example 5) poloxamer 407 was omitted, and both the triptolide and triptolide contents in the gel formulation after storage were less than 92%, indicating that both active ingredients produced a large amount of impurities during storage and had poor chemical stability. The results of the comparative tests show that the gel matrix selected by the invention can effectively inhibit the generation of impurities of triptolide and triptolide, and the compound stability of the pharmaceutical composition is expected to be good.

Claims (10)

1. The pharmaceutical composition for treating rheumatoid arthritis is characterized in that the weight ratio of active ingredients, namely glucocorticoid to a tripterygium wilfordii natural product in the pharmaceutical composition is 1: (1-5).
2. The pharmaceutical composition of claim 1, wherein the glucocorticoid is methylprednisolone or methylprednisolone aceponate.
3. The pharmaceutical composition of claim 2, wherein the natural product of tripterygium wilfordii is selected from one or more of triptolide, tripdiolide and triptolide.
4. The pharmaceutical composition of claim 3, wherein the weight ratio of methylprednisolone aceponate, triptolide and triptolide in the pharmaceutical composition is 1: (1-2): (1-2).
5. The pharmaceutical composition of claim 4, wherein the weight ratio of methylprednisolone aceponate, triptolide and triptolide in the pharmaceutical composition is 1:2:2.
6. the pharmaceutical composition of claim 5, wherein the pharmaceutical composition is a gel.
7. The pharmaceutical composition of claim 6, wherein the gelling agent comprises a gel matrix, a humectant, a solubilizer and a solvent.
8. A process for preparing a pharmaceutical composition according to claim 7, comprising the steps of:
(1) Mixing glucocorticoid, radix Tripterygii Wilfordii natural product and solubilizer to obtain medicinal liquid;
(2) Adding a humectant into the gel matrix, uniformly mixing, and uniformly mixing with the liquid medicine prepared in the step (1);
(3) And (3) adding a solvent into the solution obtained in the step (2), stirring for swelling, and standing for 24 hours to obtain the nano-composite material.
9. Use of a pharmaceutical composition according to any one of claims 1 to 7 for the manufacture of a medicament for the treatment of rheumatoid arthritis.
10. Use of a gel matrix for improving the chemical stability of a natural product of tripterygium wilfordii in a pharmaceutical composition according to any one of claims 1 to 7, wherein the gel matrix is a composition of poloxamer 407 and poloxamer 188, and the weight ratio of poloxamer 407 to poloxamer 188 is (1-5): 1.
CN202210992088.4A 2022-08-17 2022-08-17 Pharmaceutical composition containing glucocorticoid and application thereof Active CN115252626B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210992088.4A CN115252626B (en) 2022-08-17 2022-08-17 Pharmaceutical composition containing glucocorticoid and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210992088.4A CN115252626B (en) 2022-08-17 2022-08-17 Pharmaceutical composition containing glucocorticoid and application thereof

Publications (2)

Publication Number Publication Date
CN115252626A true CN115252626A (en) 2022-11-01
CN115252626B CN115252626B (en) 2024-04-02

Family

ID=83752629

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210992088.4A Active CN115252626B (en) 2022-08-17 2022-08-17 Pharmaceutical composition containing glucocorticoid and application thereof

Country Status (1)

Country Link
CN (1) CN115252626B (en)

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1528338A (en) * 2003-10-08 2004-09-15 南昌弘益科技有限公司 Thunder godvine multi-aglycone drop pill and preparing method thereof
CN1861193A (en) * 2006-01-17 2006-11-15 四川大学 Kidney target precursor medicine, said prepn., its preparing method and application
CN101947276A (en) * 2010-09-04 2011-01-19 王福山 Chinese medicinal composition for treating rheumatic arthritis
CN105944109A (en) * 2016-05-03 2016-09-21 四川大学 Glomerulus-targeted protein nanoparticle pharmaceutical composition and application thereof
CN106994129A (en) * 2017-05-15 2017-08-01 王晓辉 The application of triptolide and its derivative in the medicine for preparing treatment and/or prevention injury of lungs disease
CN107303263A (en) * 2016-12-07 2017-10-31 中国人民解放军第二军医大学 Tripterygium glycosides nano-emulsion gel and preparation method thereof
CN110279652A (en) * 2019-06-03 2019-09-27 吉林大学 A kind of nano-emulsion gel eye drops that treating keratitis and preparation method
CN114432424A (en) * 2021-12-27 2022-05-06 南通联亚药业有限公司 Stable aluminum-plastic packaged desmopressin tablet
CN114432266A (en) * 2021-12-23 2022-05-06 南通联亚药业有限公司 Stable cyclobenzaprine hydrochloride sustained-release capsule

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1528338A (en) * 2003-10-08 2004-09-15 南昌弘益科技有限公司 Thunder godvine multi-aglycone drop pill and preparing method thereof
CN1861193A (en) * 2006-01-17 2006-11-15 四川大学 Kidney target precursor medicine, said prepn., its preparing method and application
CN101947276A (en) * 2010-09-04 2011-01-19 王福山 Chinese medicinal composition for treating rheumatic arthritis
CN105944109A (en) * 2016-05-03 2016-09-21 四川大学 Glomerulus-targeted protein nanoparticle pharmaceutical composition and application thereof
CN107303263A (en) * 2016-12-07 2017-10-31 中国人民解放军第二军医大学 Tripterygium glycosides nano-emulsion gel and preparation method thereof
CN106994129A (en) * 2017-05-15 2017-08-01 王晓辉 The application of triptolide and its derivative in the medicine for preparing treatment and/or prevention injury of lungs disease
CN110279652A (en) * 2019-06-03 2019-09-27 吉林大学 A kind of nano-emulsion gel eye drops that treating keratitis and preparation method
CN114432266A (en) * 2021-12-23 2022-05-06 南通联亚药业有限公司 Stable cyclobenzaprine hydrochloride sustained-release capsule
CN114432424A (en) * 2021-12-27 2022-05-06 南通联亚药业有限公司 Stable aluminum-plastic packaged desmopressin tablet

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
刘凡;: "雷公藤多苷片联合糖皮质激素对肾病综合征患者疗效、肾功能及血清炎症因子的影响", 湖南师范大学学报(医学版), no. 05, 25 October 2017 (2017-10-25), pages 138 - 140 *
刘雪梅: "基于体内药效毒效雷公藤多苷片谱效关系研究", 《 CNKI优秀硕士学位论文全文库 医药卫生科技》, no. 1, pages 48 *
谢瑞: "单次小剂量甲氨蝶呤致重度骨髓抑制1例分析", 《中国乡村医药》, vol. 29, no. 16, pages 25 *

Also Published As

Publication number Publication date
CN115252626B (en) 2024-04-02

Similar Documents

Publication Publication Date Title
CA2688410C (en) A composition comprising camomile and black cumin oil and therapeutic uses thereof
DE112011102350T5 (en) A combination pharmaceutical composition and method for treating disorders of the genitourinary system
US7531194B2 (en) Plant extracts for the treatment of rheumatoid arthritis
KR101949810B1 (en) Sulfonamide pharmaceutical composition
DE69511448T2 (en) Use of phosphoric acid diester compounds to suppress cancer metastases in the liver
DE69021257T2 (en) Use of IFN-gamma for the manufacture of a pharmaceutical composition for the treatment of ATL.
Rusliandi et al. The anti-inflammatory activity of humic acid from Borneo peat soil in mice
CN1167466C (en) Oral medicinal preparation
CN115252626B (en) Pharmaceutical composition containing glucocorticoid and application thereof
DE60125955T2 (en) BIOACTIVE FRACTION OF EURYCOMA LONGIFOLIA
CN108354898A (en) A kind of Percutaneously administrable preparation and preparation method thereof for treating rheumatoid arthritis
KR20070054222A (en) Pharmaceutical composition with analgesic action
DE69004451T2 (en) Prophylaxis and treatment of herpes virus infections.
CN110141653B (en) A kind of composition containing total gingerol and preparation method thereof
GB2079151A (en) Medication for relief of intra-articular and intra-muscular discomfort
EP0450123B1 (en) Pharmaceutical composition for topical administration containing diclofenac-sodium
DE69826653T2 (en) BPC PEPTIDE SALTS WITH ORGAN-PROTECTIVE ACTIVITY, THEIR PREPARATION AND THERAPEUTIC USE
KR20250013306A (en) Liquid formulation comprising paeonol and apocynin
CN108309997B (en) External gel preparation for treating gouty arthritis and preparation method thereof
JP3142192B2 (en) Blood lipid improving agent and composition containing the same
JP3253878B2 (en) Formulations for iron chelation, methods of preparing the same and methods of treating Mediterranean anemia
DE102020131716A1 (en) New therapy concept for the treatment of corona infections, especially COVID-19 infections
EP2025340A1 (en) Plant extracts for the treatment of rheumatoid arthritis
KR20090079576A (en) Plant extracts for the treatment of rheumatoid arthritis
DE60005188T2 (en) GRF-CONTAINING LYOPHILIZED COMPOSITIONS

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant