[go: up one dir, main page]

WO2024155149A1 - Composition pour prévenir ou traiter des maladies de la peau à l'aide d'un agrégat nano-moléculaire de niclosamide ou de niclosamide amorphe - Google Patents

Composition pour prévenir ou traiter des maladies de la peau à l'aide d'un agrégat nano-moléculaire de niclosamide ou de niclosamide amorphe Download PDF

Info

Publication number
WO2024155149A1
WO2024155149A1 PCT/KR2024/000971 KR2024000971W WO2024155149A1 WO 2024155149 A1 WO2024155149 A1 WO 2024155149A1 KR 2024000971 W KR2024000971 W KR 2024000971W WO 2024155149 A1 WO2024155149 A1 WO 2024155149A1
Authority
WO
WIPO (PCT)
Prior art keywords
niclosamide
composition
preventing
skin diseases
skin
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.)
Ceased
Application number
PCT/KR2024/000971
Other languages
English (en)
Korean (ko)
Inventor
이혜원
김경희
김철환
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.)
Scai Therapeutics Co ltd
Original Assignee
Scai Therapeutics Co ltd
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
Priority claimed from KR1020240007386A external-priority patent/KR20240115751A/ko
Application filed by Scai Therapeutics Co ltd filed Critical Scai Therapeutics Co ltd
Publication of WO2024155149A1 publication Critical patent/WO2024155149A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • 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

Definitions

  • niclosamide or amorphous niclosamide nano-molecular complex and a composition containing the same can be used as a composition for preventing or treating skin diseases, and have excellent skin permeability.
  • Niclosamide is known to have anti-cancer and anti-inflammatory effects while minimizing host toxicity by targeting the signaling paradigm of STAT3, p65 NF- ⁇ B, and NFATc-1 through in vitro and preclinical studies.
  • Psoriasis is an autoimmune disease characterized by overproliferation of keratinocytes, which are keratinocytes, and excessive immune response.
  • Atopy is a chronic disease in which underlying inflammation deep within the skin occurs in various parts of the body due to complex genetic and environmental causes that cause abnormalities in the immune system. Rosacea is a common skin disease that causes the face to turn red and blood vessels to appear on the face.
  • the present invention has developed a composition for preventing or treating skin diseases with excellent skin permeability by making it into an amorphous nano-molecular assembly using niclosamide, thereby demonstrating the efficacy of treating psoriasis, rosacea and atopy and new methods of use. to provide.
  • the purpose of the present invention is to provide a method of using niclosamide that can prevent or treat skin diseases such as rosacea, psoriasis, atopy, etc., and a new composition for the same.
  • the present invention provides a composition for preventing or treating skin diseases containing niclosamide.
  • the present invention provides niclosamide or niclosamide molecular complex with excellent efficacy as a treatment for skin diseases, and has the advantage of controlling or suppressing inflammatory gene expression in vivo over Ivermectin, a conventional treatment for rosacea, or Imiquimod, a psoriasis treatment. Since it has superior skin permeability than existing products, it provides a new method of use and a composition reflecting this that can prevent or treat skin diseases such as rosacea, psoriasis, and atopy.
  • Figure 1 is a photograph of Bled generated after LL37 was injected into mouse skin to conduct a rosacea efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 3 is a photograph taken of the erythema area analysis during the rosacea efficacy test of the molecular assembly composition according to an embodiment of the present invention and a graph of the results.
  • Figure 4 is a photograph of the H&E results during a rosacea efficacy test of a molecular assembly composition according to an embodiment of the present invention and a graph of the results.
  • Figure 5 is a photograph of Gr1+ staining results and a graph of the results during a rosacea efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 6 is a photograph of the mast cell staining results during a rosacea efficacy test of a molecular assembly composition according to an embodiment of the present invention and a graph of the results.
  • Figure 8 is a graph showing real-time PCR results during a rosacea efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 9 is another graph showing real-time PCR results during a rosacea efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 10 is a photograph and graph summarizing the results of a rosacea efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 11 is a photograph of the results of a preliminary test on a psoriasis animal model during a psoriasis efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 13 is a photograph of the H&E results of a psoriasis animal model during a psoriasis efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 14 is a photograph taken of the skin thickness measurement results of a psoriasis animal model during a psoriasis efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 16 is a graph summarizing the visual evaluation of a psoriasis animal model during a psoriasis efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 18 is a graph summarizing the results of skin thickness measurement on a psoriasis animal model during a psoriasis efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 19 is a graph summarizing the gene expression results of a preliminary experiment on a psoriasis animal model during a psoriasis efficacy test of a molecular complex composition according to an embodiment of the present invention.
  • Figure 21 is a photograph taken of efficacy evaluation on an atopic dermatitis animal model during an atopic efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • Figure 22 is a graph summarizing the cytotoxicity evaluation of the molecular assembly composition and niclosamide according to an embodiment of the present invention.
  • Figure 24 is a graph confirming the results of a TNF ⁇ -induced inflammation model experiment using the Hacat cell line according to an embodiment of the present invention.
  • Figure 25 shows the conditions after setting HPLC-UV analysis conditions to quantitatively analyze the amount of niclosamide during a skin permeation test of niclosamide, niclosamide molecular complex, and composition using the same according to an embodiment of the present invention. This is a graph about the drug peak and standard curve.
  • Figure 28 is a graph of the results of an in-vitro skin deposition experiment measured after 4 hours according to the ethanol concentration of niclosamide according to an embodiment of the present invention.
  • Figure 29 is a photograph of an image of skin with dehydration in the skin caused by ethanol after 4 hours according to an embodiment of the present invention.
  • Figure 31 is a graph showing the results of an in-vitro skin permeation experiment for each group according to an embodiment of the present invention.
  • Figure 32 is a graph showing the results of an in-vitro skin deposition experiment after 0.5, 1, and 3 hours according to an embodiment of the present invention.
  • Figure 33 is a graph showing the results of an in-vivo skin deposition experiment according to an embodiment of the present invention.
  • Figure 35 is a schematic diagram of the experimental period of a psoriasis efficacy test of a molecular assembly composition according to an embodiment of the present invention.
  • the present invention relates to a molecular association in which niclosamide is physically bonded, and when the molecular association is formed of a composition containing water, the molecular association in the composition is an amorphous molecular association having an aggregated structure. provides.
  • composition for preventing or treating skin diseases comprising amorphous sunitinib nano-molecular complex
  • the present invention provides a composition for preventing or treating skin diseases containing niclosamide.
  • the molecular assembly is a molecular assembly to which niclosamide is physically bonded, as discussed above, and when the molecular assembly is formed of a composition containing water,
  • the molecular association may be an amorphous molecular association having a condensed structure.
  • composition for preventing or treating skin diseases of the present invention contains niclosamide as described above, it can have the effect of promoting skin penetration.
  • the skin diseases include rosacea, psoriasis, atopy, scleroderma, ichthyosis, Bowen's disease, papilloma, eczema, toxic eczema, acne vulgaris, and seborrheic dermatitis. It may be a composition for preventing or treating one or more skin diseases selected from the group consisting of dermatitis, lichen planus, striae, pediculosis, and seborrheic keratosis.
  • the composition may include at least one pharmaceutically acceptable vehicle or at least one pharmaceutically acceptable additive.
  • the surfactant may be any one or more from the group consisting of polyoxyethylene-polyoxypropylene copolymer (poloxamer), sorbitan ester (Span), polyoxyethylene sorbitan (Tween), and polyoxyethylene ether (Brij). You can.
  • the composition uses polyoxyethylene sorbitan (Tween) as a surfactant;
  • a silica carrier is used as a carrier;
  • Sodium bicarbonate may be further included, but are not limited thereto.
  • the pharmaceutical composition can be used in the form of a transdermal medication.
  • the external agent is any one selected from the group consisting of solution, external ointment, cream, foam, emulsion, suspension, emulsion, paste, gel, lotion, powder, and spray. It can be used in the form of .
  • Example 1 Amorphous niclosamide nanomolecular assembly (SCAI-502)
  • Niclosamide (Olon) 60.0 g was dissolved in 12.0 kg of ethanol (94.5% Ethanol, Daejeong Chemical) to prepare a niclosamide solution with a concentration of about 0.5%.
  • 15.4 g of NaHCO 3 Sodium bicarbonate, Daejeong Chemical Gold
  • 168.0 g of purified water was dissolved in 168.0 g of purified water and mixed with the niclosamide solution to prepare the first niclosamide mixture.
  • 7.8 g of Na 2 SO 4 (Sodium Sulfate, Daejeong Chemical Gold) was dissolved in 72.0 g of purified water and mixed with the first niclosamide mixture to prepare the second niclosamide mixture.
  • the niclosamide secondary mixture was filtered through a 1 ⁇ m paper filter to remove undissolved solids, and the niclosamide filtrate was collected.
  • SYLOID 244FP (GRACE, USA) was wetted with 4.8 kg of 94.5% ethanol.
  • a 1.00 ⁇ m paper filter was prepared by combining a Nutsche filter with a diameter of 350 mm.
  • a SYLOID 244FP column with a height of approximately 1.5 cm was prepared by pouring the SYLOID 244FP solution soaked in ethanol into the Nutsche filter.
  • the combined weight of the first and second effluents was 22.11 kg. Filtration and concentration were performed. 18.0 kg of MTBE (tert-butyl methyl ether, Daejeong Chemical Gold) was added to the reactor, and the concentrate was added dropwise to produce an amorphous niclosamide molecular complex. After processing the 0.45 ⁇ m PTFE-H membrane filter and recovering the filtered cake, 29.0 g (Y.48%) of amorphous niclosamide molecular complex was obtained using a vacuum dryer.
  • MTBE tert-butyl methyl ether, Daejeong Chemical Gold
  • SYLOID 244FP (GRACE, USA) was wetted with 501.49 g of 94.5% ethanol.
  • a vacuum filtration type After placing a 0.45 ⁇ m PVDF membrane filter on a Buchner funnel with a diameter of 155 mm, pour the SYLOID 244FP solution soaked in ethanol into the Buchner funnel and add a SYLOID 244FP column about 1 cm high. ) was prepared.
  • amorphous niclosamide molecular complex concentrate 228.78 g of XDP3050 (GRACE, USA) were mixed with a mixer.
  • NCSHW128A was obtained.
  • niclosamide, DS-niclosamide, and ivermectin are all used dissolved in 100% ethanol.
  • paraffin sections were made from 10% formalin-fixed tissues, cut to 4 ⁇ m, and then subjected to H&E staining, Toluidin-blue staining for mast cell staining, and fluorescent staining to see Gr1 (monocyte & neutrophil marker) and CD31. Implemented.
  • Redness area was measured using image J. Redness Area Area calculation results showed that the erythema reaction was statistically significantly reduced in both the niclosamide (API group) and DS-treated groups when compared to the vehicle (100% EtOH) and ivermectin groups (Figure 3).
  • Gr1 is a marker that confirms the infiltration of inflammatory cells, that is, an increase in neutrophils, which make up the largest portion of various inflammatory cells.
  • Gr1 (+) was statistically significant in niclosamide and DS. ) It was confirmed that the number of cells decreased. ( Figure 5)
  • CD31 a glycoprotein called PECAM-1
  • PECAM-1 a glycoprotein called PECAM-1
  • tissue test results and the gene expression analysis analyzed by PCR are expected to indicate that ethanol used as a vehicle affected gene expression, and it is necessary to confirm whether it is a suitable solvent for experiments on rosacea disease (FIG. 10).
  • niclosamide treatment concentration The first experiment was conducted only with 1% niclosamide and 0.2% niclosamide containing additional substances to improve penetration. The second experiment was conducted using 0.2% niclosamide, 1% niclosamide, and 0.2% and 1% with DDS to improve their penetration. Since psoriasis lesions began to appear prominently from the 3rd day of application of Imiquimod, the degree of skin inflammation was visually observed and recorded.
  • RNA is isolated from frozen tissue for gene expression analysis. Using 4ug of total RNA, cDNA was synthesized using oligo-dT, and psoriasis-related cytokine expression was confirmed using real-time PCR.
  • the gene list analyzed a total of 6 items: IL1 ⁇ , IL6, IL12, IL17A, IL23, and TNF ⁇ .
  • the graph is Mean ⁇ SEM, and the data analysis was conducted by comparing the group with the vehicle treatment group through one-way ANOVA (Dunnett's post-hoc test). * means p ⁇ 0.05, **p ⁇ 0.01, n.s means non-significant.
  • the program uses GraphPad Prism.
  • DNCB 1% DNCB was instilled after shaving and instilled again on the 4th day to induce sensitization. After sensitization, DNCB 0.4% was evenly applied topically to the back of the mouse three times a week for the next three weeks from Day 0. After 2 weeks, apply vehicle or niclosamide topically every day for 2 weeks.
  • Cytotoxicity evaluation To evaluate cytotoxicity, niclosamide was dissolved in DMSO and treated according to concentration using human keratinocytes and Hacat cell line. After treatment at each concentration, cytotoxicity was evaluated using microscopic observation and WST-1. It was confirmed that there was no cytotoxicity in human keratinocytes at a concentration of 0.1uM. (Microscopic observation) Hacat confirmed that there was no cytotoxicity up to a concentration of 0.5uM. (measured by WST-1)
  • Keratinocytes were seeded in 24 wells at approximately 30% of KGM medium. The concentration of KLK5 was measured by ELISA using the culture supernatant at 48 and 72 hours after pretreatment with niclosamide (0.1uM) and ivermectin (1uM) for about 16 hours as a positive control and 100nM calcotriol.
  • Hacat cell line was 100% confluent and serum starvation was performed for 24 hours. After pretreatment with niclosamide (0.5uM) and ivermectin (1uM), a positive control, for 2 hours, treatment was performed with 10ng/ml TNF ⁇ for 24 hours. Total RNA was isolated from cells, cDNA was synthesized, and IL1 ⁇ , IL6, and IL8 expression was confirmed by real-time PCR.
  • HPLC-UV analysis conditions are as follows.
  • UV part Wavelength - 245nm
  • LC-MS/MS analysis method was established to quantify the amount of niclosamide accumulated in the skin.
  • Valsartan 100ng/mL in acetonitrile solution
  • the pretreatment process was as follows: 200 ⁇ L of IS solution was added to 50 ⁇ L of skin extract diluted with ethanol, vortexed for 5 minutes, and centrifuged at 13,200 rpm for 5 minutes. Afterwards, the supernatant was injected into LC-MS/MS and the concentration of niclosamide was analyzed under the following conditions.
  • niclosamide Prior to the skin permeation test of niclosamide, seven solvents were selected and a solubility test was conducted to select the receptor fluid in the Franz diffusion cell device.
  • the solubility test method is as follows: First, put an excess amount of niclosamide into an ep tube containing each solvent and then vortex at room temperature for 24 hours. Afterwards, it was centrifuged at 13,200 rpm for 5 minutes and filtered using a syringe filter (0.2 ⁇ m). This was appropriately diluted with ethanol and then quantified using the previously established LC-MS/MS analysis method.
  • a preliminary skin permeation experiment was conducted using a Franz diffusion cell to confirm the skin permeation effect according to the ethanol composition in the receptor fluid.
  • the experimental method was as follows: The day before, a Balb/c mouse (8 weeks, male) had hair removed over a wide area on the back using an epilator and hair removal cream. On the day of the experiment, the mouse was sacrificed and the skin was carefully obtained using scissors. After fixing the cut mouse skin on the Franz diffusion cell, fill the receptor part with 50%, 90%, or 100% ethanol. After adding 1 mL of 0.2% niclosamide to the donor part, 0.5 mL of receptor solution was collected through the sampling port at a predetermined time. Immediately after collection, the same amount of ethanol was added to the receptor chamber. The collected samples were centrifuged at 13,200 rpm for 10 minutes, and the supernatant was appropriately diluted with ethanol and analyzed by LC-MS/MS.
  • the permeation amount of niclosamide over time for a certain area of skin was the same as (Figure 27), and the flux, permeability coefficient, and lag time values of each group were the same as (Table 3).
  • the permeation amount of niclosamide over time in the 100% ethanol group was significantly greater than that of the other groups, and the permeation amount was similar for the 90% ethanol group that satisfied the sink condition and the 50% ethanol group that did not satisfy the sink condition.
  • the skin was fixed between the donor and receptor chamber. After filling the receptor part with 50% or 100% ethanol, add 1 mL of 0.2% niclosamide to the donor part. After removing the donor and drug at a predetermined time, the mouse's skin is carefully cut to fit the administration area. After cleansing the skin surface with ethanol and water, finely chop the skin, freeze it in liquid nitrogen, and finely grind it using a mortar and pestle until it turns into powder. After treating with 1 mL of ethanol, niclosamide accumulated in the skin was extracted using vortexing and bath sonic. Afterwards, centrifugation was performed at 13,200 rpm for 10 minutes, and the supernatant was pretreated and then subjected to LC-MS/MS analysis.
  • mouse skin was mounted on the Franz diffusion cell and the receptor part was filled with 50% ethanol.
  • receptor fluid is collected from the sampling port at predetermined times (1, 3, 5, 8, 12 hours), and immediately after, the same amount of 50% ethanol is replenished into the receptor chamber.
  • the collected receptor fluid was appropriately diluted with ethanol and then analyzed using HPLC.
  • the API group showed the highest skin residual amount compared to the experimental group (DDS 1st, DDS 2nd), and at 3 hours, the highest skin residual amount was in that order: DDS 2nd formulation, API, and DDS 1st formulation. showed.

Landscapes

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

Abstract

La présente invention démontre qu'une composition contenant un agrégat nano-moléculaire de niclosamide ou de niclosamide amorphe peut être utilisée en tant que composition pour prévenir ou traiter des maladies de la peau.
PCT/KR2024/000971 2023-01-19 2024-01-19 Composition pour prévenir ou traiter des maladies de la peau à l'aide d'un agrégat nano-moléculaire de niclosamide ou de niclosamide amorphe Ceased WO2024155149A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR10-2023-0008320 2023-01-19
KR20230008320 2023-01-19
KR1020240007386A KR20240115751A (ko) 2023-01-19 2024-01-17 니클로사미드 또는 무정형 니클로사미드 나노 분자회합체를 이용한 피부 질환 예방 또는 치료용 조성물
KR10-2024-0007386 2024-01-17

Publications (1)

Publication Number Publication Date
WO2024155149A1 true WO2024155149A1 (fr) 2024-07-25

Family

ID=91956356

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2024/000971 Ceased WO2024155149A1 (fr) 2023-01-19 2024-01-19 Composition pour prévenir ou traiter des maladies de la peau à l'aide d'un agrégat nano-moléculaire de niclosamide ou de niclosamide amorphe

Country Status (1)

Country Link
WO (1) WO2024155149A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180081936A (ko) * 2017-01-09 2018-07-18 연세대학교 산학협력단 니클로사마이드를 함유하는 Axin-GSK3 단백질 결합 관련 질환 치료용 약학조성물
KR20210061352A (ko) * 2018-08-24 2021-05-27 유니온 테라퓨틱스 에이/에스 피부염의 치료를 위한 할로겐화 살리실아닐리드
KR20210128939A (ko) * 2020-04-17 2021-10-27 영남대학교 산학협력단 경구 생체 이용률이 증가된 니클로사마이드 함유 고체분산체 및 이의 제조방법
KR20220063082A (ko) * 2020-11-09 2022-05-17 주식회사 스카이테라퓨틱스 고상의 물질 및 이를 포함하는 분산 조성물
KR20230053542A (ko) * 2021-10-14 2023-04-21 주식회사 스카이테라퓨틱스 유기물, 무기물 또는 이들의 염으로 이루어진 나노 분자 회합체

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20180081936A (ko) * 2017-01-09 2018-07-18 연세대학교 산학협력단 니클로사마이드를 함유하는 Axin-GSK3 단백질 결합 관련 질환 치료용 약학조성물
KR20210061352A (ko) * 2018-08-24 2021-05-27 유니온 테라퓨틱스 에이/에스 피부염의 치료를 위한 할로겐화 살리실아닐리드
KR20210128939A (ko) * 2020-04-17 2021-10-27 영남대학교 산학협력단 경구 생체 이용률이 증가된 니클로사마이드 함유 고체분산체 및 이의 제조방법
KR20220063082A (ko) * 2020-11-09 2022-05-17 주식회사 스카이테라퓨틱스 고상의 물질 및 이를 포함하는 분산 조성물
KR20230053542A (ko) * 2021-10-14 2023-04-21 주식회사 스카이테라퓨틱스 유기물, 무기물 또는 이들의 염으로 이루어진 나노 분자 회합체

Similar Documents

Publication Publication Date Title
WO2019004738A2 (fr) Utilisation d'une composition comprenant un exosome dérivé de cellules souches adipeuses en tant que principe actif pour atténuer la dermatite
Busbridge et al. Stress and the single cytokine: interleukin modulation of the pituitary-adrenal axis
WO2011032491A1 (fr) Extrait de prunelle vulgaire contenant de l'acide rosmarinique, son procédé de préparation et son utilisation pour la préparation d'un médicament pour la prévention ou le traitement de la métastase du cancer après une chirurgie
WO2013176471A1 (fr) Composition pharmaceutique pour la prévention ou le traitement de maladies médiées par stat-3, contenant un extrait ou une fraction de salvia plebeia r. br. en tant que principe actif
WO2021029541A1 (fr) Composition de liposome élastique comprenant un tensioactif à base de saccharose et composition cosmétique la contenant
WO2020116810A1 (fr) Composition pharmaceutique, comprenant un peptide inhibiteur contre la signalisation fas, destinée à la prévention ou au traitement de l'obésité, du foie gras, ou de la stéatohépatite
WO2010117194A2 (fr) Composition pour prévenir ou traiter des troubles gastriques contenant un composant actif comprenant un composé de la série des acides gras
WO2024155149A1 (fr) Composition pour prévenir ou traiter des maladies de la peau à l'aide d'un agrégat nano-moléculaire de niclosamide ou de niclosamide amorphe
WO2013187552A1 (fr) Composition anti-inflammatoire comprenant un alloféron et composition cosmétique la comprenant
WO2019045214A1 (fr) Composition pour la prévention ou le traitement de la dermatite atopique
WO2020032365A1 (fr) Composition, comprenant un composé de ginsénoside, pour la prévention ou le traitement d'une maladie inflammatoire médiée par des inflammasomes
WO2023055009A1 (fr) Peptide présentant une activité anti-inflammatoire et utilisation correspondante
WO2022231083A1 (fr) Composition pour la prévention ou le traitement d'une maladie auto-immune, comprenant des mitochondries en tant que principe actif
WO2023048453A1 (fr) Nanoparticules comprenant des dimères de médicament et leur utilisation
WO2020149538A1 (fr) Composition pharmaceutique comprenant des cellules souches clonales pour la prévention ou le traitement de la dermatite atopique
WO2020241925A1 (fr) Complexe de nanoparticules lipidiques capturant un aptide fusionné avec un matériau pénétrant dans les cellules et son utilisation
WO2021221472A1 (fr) Particules de micelle comprenant du ginsénoside amphipathique, composition comprenant ces dernieres et leur procédé de préparation
WO2024049167A1 (fr) Nouveau sel de niclosamide, son agrégat moléculaire et composition pharmaceutique le contenant
WO2024215162A1 (fr) Protéine de fusion unique et composition pharmaceutique la comprenant
WO2016175589A2 (fr) Composition pharmaceutique pour la prévention ou le traitement de maladies respiratoires, contenant un extrait de mélange de plantes médicinales
WO2023022569A1 (fr) Méthode de traitement de maladies immunitaires au moyen d'un inhibiteur de la calcineurine et de cellules souches
WO2015023165A1 (fr) Composite de régulation d'une inflammation et cellules souches mésenchymateuse stabilisées ayant une fonction optimisée de régulation de l'immunité par blocage de la molécule de signalisation stat3
WO2023163539A1 (fr) Utilisation d'un nouveau dérivé de pomalidomide pour traiter des maladies cérébrales
EP1631283A1 (fr) Combinaisons antiarthritiques
WO2020213906A1 (fr) Composition pharmaceutique comprenant un extrait d'un mélange de plantes médicinales pour le traitement de la bronchopneumopathie chronique obstructive

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24744928

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE