WO2023089462A1 - Produits médicinaux à base d'exosomes dérivés de plantes, d'humains, d'algues, et de champignons médicinaux pour traiter des maladies de la peau - Google Patents
Produits médicinaux à base d'exosomes dérivés de plantes, d'humains, d'algues, et de champignons médicinaux pour traiter des maladies de la peau Download PDFInfo
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Definitions
- the invention of medicinal products based on plant exosomes, algae, and medicinal mushrooms to treat skin diseases are beneficial compounds, which have been selected from the extracts and essences of the intended plant families in accordance with the disease target. They are made with purified exosomes from the above-listed plants, spirulina algae, and shiitake mushrooms. Plant-derived exosomes have a structure similar to exosomes isolated from mammals and act as extracellular messengers in intercellular communication. Moreover, these vesicles are capable of transferring mRNAs, microRNAs (miRNAs), bioactive lipids, and proteins to human and animal cells.
- miRNAs microRNAs
- a topical composition for regulating skin conditions comprises an effective amount of isolated exosomes having increased levels of heat shock stress-response molecules and a carrier.
- the isolated exosomes are obtained from a plant's leaf flesh conditioned by growing the plant under conditions that include a heat shock of the plant at a temperature of about 33°C to about 45°C for about 1 hour to about 3 hours.
- exosome-containing compositions for regulating human skin include inducing increased skin integrity by cell renewal, enhancing water content or moisture of the skin, reducing transepidermal water loss, skin flaking, and scaling, improving skin thickness, enhancing skin tensile properties, reducing the appearance of dermal fine lines and wrinkles, improving skin texture, reducing skin pores size, enhancing skin smoothness, improving skin age spots, improving skin tone, and improving the appearance of scars and skin abrasions.
- compositions are provided, along with methods for their preparation and use for regulating skin condition.
- the compositions provided contain isolated stem cell exosomes having increased levels of heat shock stress-response molecules.
- Uses of the exosome-containing compositions for regulating human skin include inducing increased skin integrity by cell renewal, enhancing water content or moisture of the skin, reducing transepidermal water loss, skin flaking, and scaling, improving skin thickness, enhancing skin tensile properties, reducing the appearance of dermal fine lines and wrinkles, improving skin texture, reducing skin pores size, enhancing skin smoothness, improving skin age spots, improving skin tone, and improving the appearance of scars and skin abrasions.
- a composition comprising an exosome and/or extracellular vesicle derived from stem cell as an active ingredient and its application for reinforcing or improving skin barrier
- compositions for reinforcement and functional improvement of the skin barrier comprising at least one member selected from the group consisting of a stem cell-derived exosome and/or extracellular vesicle, and fractions containing the exosome and/or extracellular vesicle isolated from a stem cell culture medium, as an effective ingredient.
- the composition of the present invention can improve the water loss index of the stratum corneum, such as transepidermal water loss (TEWL), and increase skin hydration. Therefore, the composition of the present invention can be effectively used as a cosmetic composition, an external preparation for skin, and a pharmaceutical composition for reinforcement and functional improvement of the skin barrier.
- TEWL transepidermal water loss
- the present invention provides a composition for reducing pores, comprising stem cell-derived exosomes as an active ingredient, and a beauty method for reducing skin pores using the composition. Treating the skin with the composition for reducing pores comprising stem cell-derived exosomes as an active ingredient, according to the present invention, has an excellent skin beauty benefit of reducing skin pores, particularly skin pores of the face, improving the appearance of the face.
- the invention discloses a method for applying stem cell exosomes to a facial mask, which comprises the following components in parts by weight: 1-5 parts of cogongrass extract, 2-4 parts of chamomile, 1-3 parts of trehalose, 5-15 parts of avocado, 2-5 parts of calendula, 4-6 parts of peppermint oil, 10-15 parts of honeysuckle, 5-10 parts of radix ophiopogonin, 1-3 parts of cysteine, 1-3 parts of serine, 1-3 parts of thymine, 1-2 parts of cytosine and 1-2 parts of silk.
- the method for applying the stem cell exosome to the facial mask extracts the lalang grass rhizome extract and the chamomile, obtains extract liquid, and mixes the extracted liquid with the secretion body dry ice powder, can increase the water replenishing capacity and the water locking capacity of the facial mask to the skin, simultaneously mixes trehalose in the raw materials, increases the calming effect of the facial mask to the skin on the basis of the original raw materials, enables material molecules to be in a stable state, is convenient for the skin tissue to fully absorb internal nutrient substances, and promotes the metabolism of the skin tissue.
- Exosomes derived from stem cells can be used to repair skin wounds, reduce immune responses and inflammation, strengthen angiogenesis, reproduce skin cells, and regenerate collagen. Also, in the experiments conducted on diabetic patients, it caused wound healing and can also be used as a drug carrier.
- HDFs human dermal fibroblasts
- TGF- ⁇ tumor necrosis factor alpha
- TGF- ⁇ transforming growth factor beta
- hiPSC-MSCs mesenchymal stem cells derived from human induced pluripotent stem cells
- exosomes enriched with fibrin gel are a promising strategy for promoting chronic wound healing and complete skin regeneration.
- exosomes were purified from platelets and combined with injectable fibrin sealant (TISSEEL) and used to heal wounds created in rabbit ears.
- TISSEEL injectable fibrin sealant
- the main goal of this invention is to produce medicinal compounds based on plant exosomes with immunogenic properties and without any allergic effects, blood serum of each person completely specifically, edible shiitake mushroom and spirulina algae for skin treatments of eczema, blemishes and melasma, sagging and skin aging, cellular regeneration of human skin, as well as increasing the water or moisture content of the skin, preventing skin flaking, improving skin thickness, increasing skin elasticity, removing skin moles, removing skin acne, improving skin texture, reducing pore size skin, increasing skin smoothness, improving skin aging spots, improving skin color and improving the appearance of wounds and healing wounds in diabetic people, for this purpose, by identifying the native species of Iran, medicinal and health compounds based on plant exosomes and Algae and medicinal mushrooms were selected that are suitable for experimental research in the future.
- Exosomes are secreted from different cells, including stem cells, containing different molecules such as growth factors, proteins, broken nucleic acids, and microRNAs (miRNAs).
- Mesenchymal stem cells contain exosomes that carry out actions the same as the mesenchymal stem cells, including repair of tissue damage, inhibition of inflammatory responses, and regulation of the immune system.
- Using exosomes does not have risks such as aneuploidy and transplant (graft) rejection. To this end, they can be exploited for the treatment of illnesses such as autoimmune disease and cancer.
- Plant-derived exosomes have a structure similar to exosomes isolated from mammals and operate as extracellular messengers in intercellular communication.
- exosomes are capable of delivering mRNAs, microRNAs (miRNAs), bioactive lipids, and proteins into animal cells. Concerning the gained results, using exosomes obtained from plants and humans to treat hyperpigmentation and rejuvenation is a suitable approach for the future of the cosmetics industry. Additionally, plant-derived exosomes are safe for the environment due to their small size, low toxicity, and high absorption; as a result, they can act as the next generation of drug delivery systems for treating multiple diseases. Furthermore, since some individuals are allergic to herbal compounds, so medicinal compounds based on the exosomes from the subjects' blood serum are specifically used.
- Melanin is a critical component of the human hair, eye, and skin pigmentary system, which is produced by melanocytes through the melanogenesis process. Abnormal accumulation of melanin causes skin problems such as freckles, solar lentigo and melasma, as well as cancer and vitiligo. Hence, the regulation of melanogenesis is a vital strategy to treat hyperpigmentation disorders.
- hydroquinone is a hydroxyphenol chemical compound, which interferes with the activity of tyrosinase and is utilized as a skin-lightening agent in the cosmetic industry.
- hydroquinone may lead to side effects such as contact dermatitis and exogenous ochronosis (EO).
- Tretinoin also known as all-trans retinoic acid (ATRA)
- ATRA all-trans retinoic acid
- Type I Collagen 80 to 85%
- Type III Collagen 10 to 15%
- an enhancement is observed in the amount of type III collagen.
- multiple anti-aging strategies including cosmetics, chemical peels, phototherapy, and micro-needling, have been developed so far. Nevertheless, the generated improvement through these methods has been less durable; thus, finding approaches for the durability of anti-aging effects has today attracted much attention.
- Exosomes are found in body fluids such as saliva, blood, urine, serum, etc. A collection of evidence represents that exosomes have a crucial role in intercellular communication in physiological and pathological conditions. Besides, they enjoy the capability of passing through the membrane and protecting the degradation of proteins and RNAs contained in them and have the potential of transferring various compounds to the cell. Because of the features such as receptor specificity, not stimulating the immune system, and engineering them as drug carriers, exosomes have been introduced as an agent for the transfer of genetic material and the treatment of diseases. Exosomes are secreted from different cells, including stem cells, containing different molecules such as growth factors, proteins, broken nucleic acids, and microRNAs (miRNAs).
- miRNAs microRNAs
- Exosomes have different contents on the basis of the cell origin from which they are released. Exosomes can penetrate into the axon and regulate the inner mechanism of nerve repair and interfere in the repair of peripheral nerves and the recovery of the damaged area.
- Mesenchymal stem cells contain exosomes that carry out actions the same as the mesenchymal stem cells, including repair of tissue damage, inhibition of inflammatory responses, and regulation of the immune system. Using exosomes does not have risks such as aneuploidy and transplant (graft) rejection. To this end, they could be exploited in treating diseases such as autoimmunity and cancer as pharmaceutical compounds and nanocarriers to transfer drugs and genes.
- ADSCs-EXO compounds modulate immune and inflammatory responses at the site of the created wounds, as well as cause the strengthening of angiogenesis, skin cell reproduction, and collagen regeneration, and prevent wound hyperplasia.
- ADSCs have high stability and are not rejected by the immune system rather than ADSCs-EXO drugs, and their dosage can be simply controlled.
- the above-listed compounds can operate as a combined carrier and scaffold for treatment, resulting in skin repair without scarring.
- UMB-MSCs Human umbilical cord blood-derived mesenchymal stem cells
- UB-MSCs Human umbilical cord blood-derived mesenchymal stem cells
- USC-CM Human umbilical cord blood-derived mesenchymal stem cells
- HDFs human dermal fibroblasts
- USC-CM EXOs are absorbed in human skin and boost the synthesis of type I collagen and elastin in the skin, which is critical for rejuvenating the skin.
- HDFs human dermal fibroblasts
- HDF-XO Human dermal fibroblast-derived exosomes
- TGF- ⁇ tumor necrosis factor-alpha
- TGF- ⁇ tumor necrosis factor beta
- exosomes obtained from plants, humans, algae, and edible mushrooms are safe for the environment because of their small size, low toxicity, and high absorption; thus, they can operate as the next generation of drug delivery systems for treating a lot of diseases.
- plant-derived exosomes can be utilized to decrease melanin and free radicals, thereby lightening and rejuvenating the skin. Nevertheless, exosomes possibly have a toxic effect on the skin. Thus, other additional tests such as an allergy skin test or an Ames test should be done as well.
- Nano Aloe Vera for more effective skin care
- Nano Quercetin for delaying cell damage caused by UV rays
- Nano Fullerene for collagen regeneration and protection against skin aging
- Nano Lutein for maintaining antioxidant activity
- Nano-Resveratrol for protecting the skin against ultraviolet rays
- Medicinal products based on exosomes are limited to developed countries worldwide and the expense of their production to treat various diseases is very high. Therefore, the treatment of many incurable skin diseases with minimal costs can be achieved by using exosomes extracted from the extracts and medicinal compounds of plants, blood serum of people, medicinal mushrooms, and algae.
- the current invention can be a benchmark for the improvement of wound healing, collagen formation, reduction of water loss in the stratum corneum (SC) area, skin treatments for eczema, blemishes and melasma, skin sagging & aging.
- SC stratum corneum
- it can be beneficially exploited as a cosmetic and medicinal combination to strengthen and improve the function and quality of the skin.
- Medicinal compounds made respectively contain exosomes derived from the extract and essence of plants of the mint family, umbrellas, Rosaceae, borage, beech family (Fagaceae), Dwarf Pomegranate (Punica granatum L. var.
- the exosomes derived from the extracts and essences of the studied plants and the blood serum of the subjects in the investigation were mixed with the intended cosmetic compounds.
- the gene expressions of Collagen I, Collagen III, Homo sapiens prolyl 4-hydroxylase subunit alpha 1, and Elastin were examined using tissue real-time PCR.
- the techniques to evaluate the toxic properties of extracted exosomes and their survival rates measuring the absorption of cells having exosomes, melanin content in cells through examining the activity of tyrosinase enzyme, measuring the bleaching effect in human models, measuring the size of exosomes by DLS method, shape and size range of exosomes by TEM method were explored.
- an allergy skin test was also performed to assess the toxicity effect of exosomes on the skin, and the results of the preliminary experiments demonstrated that the product in question can be a desirable choice for future empirical studies.
- plants from the above-listed families, as well as spirulina algae and shiitake mushrooms, are chosen and gathered or purchased with respect to the target of the disease.
- the formulation, content, and composition of the constituent components vary regarding the type of product. For example, two phases of water and oil are typically utilized for the preparation of creams, lotions, and serums. These two components are kept together by an emulsifier. Moreover, antioxidants, preservatives, pH regulators, fragrances, additives, and active substances are also exploited in skin product formulations.
- the exosome extraction kit with the brand name Exocib S which was prepared and purchased from ANACELL (Supernatants), includes two solutions A and B, in which solution A was heated at a temperature of 37 degrees Celsius during the time interval of centrifugation in accordance with the sent instructions until no crystals remain in the solution and a completely transparent solution is achieved. To do so, some water is poured into a large petri dish, and a regular thermometer is placed in it, the container of the solution is held in the water for a few minutes with your hand, and it was vortexed after a few minutes so that a clear solution is obtained.
- a ratio of 5:1 extract sample 5 and solution A in a ratio of 1 was taken from the serum samples in both groups, and the solution A in the exosome extraction kit using sampler in microliters and moved into the new microtube. After each dilution, the microtubes were vortexed for a few minutes. Then, they were transferred to a refrigerator with a temperature of 4 degrees and incubated for 12 hours. The specimens gained from the previous step were vortexed for 1 minute to make them homogenous. Next, centrifugation was performed again for 40 minutes at 4 degrees with a speed of 3000 rpm, and the upper solution was discarded. After that, 50 microliters of solution B were added to the remaining solution according to the standard protocol of the kit manufacturer, and the microtubes were transferred to a temperature of -20°C and stored.
- exosomes contain combinations of nucleic acids, DNA, RNA, and protein
- light absorption was measured at wavelengths of 260 to 280 nm using a spectrophotometer.
- the spectrophotometric technique is on the basis of the amount of transmitting or absorbing ultraviolet light by the substance.
- the samples are exposed to ultraviolet light at a wavelength of 260 nm (260 A).
- 260 A the absorption of light at 260 nm by the sample is more, the nucleic acid concentration in the sample containing the exosome will be higher.
- high light absorption at 280 nm represents an enhancement in protein content in the extracted product. Therefore, the spectrophotometry method was exploited to confirm the presence of exosomes in cosmetic products, and it was compared with medicinal and cosmetic products without exosomes.
- This technique operates as the measurement of the Brownian motion related to the hydrodynamic diameter based on Stokes-Einstein.
- the results of DLS are declared in three forms: intensity, volume, and number.
- the solvent used was phosphate buffer to specify the diameter size of exosomes by the DLS technique, and its refractive index is 1.33 with a viscosity of 1.64.
- the desired device is the Particle Size Analyze of Cordouan Company, Vasco3 model, France, where the size of existing particles is determined using light radiation and scattering.
- more than 80% of the extracted vesicles have a size of less than 100 nm, reflecting the presence of exosomes derived from plant samples, spirulina algae, and Shiitake medicinal mushrooms.
- exosomes In order to examine the toxicity of exosomes on skin cells, they were kept in a CO2 incubator at 37 degrees after defrosting and culturing the cells in the desired medium, and the cells were passaged three days later. Then, the toxicity of the exosome was assessed on skin cells at different times of 24, 48, and 72 hours after incubation using an MTT assay.
- exosome-based medicinal compounds For assessing the efficacy of exosome-based medicinal compounds on humans, about 50 healthy people and 50 people with skin eczema diseases, all kinds of skin pimples, hives, burns, skin spots, and skin cracks were chosen under the supervision of an allergy specialist.
- an allergy test was done to examine the toxicity effect of exosomes on the skin of subjects. After assurance of the non-allergenicity of the investigated subjects to medicinal compounds based on exosomes, clinical experiments on the remaining subjects were conducted, and macroscopic evaluation before and after the treatment was done. It is worth mentioning that some individuals were allergic to the herbal compounds employed; thus, medicinal compounds based on the exosomes from the subjects' blood serum were specifically used (table 6).
- This invention provides our need in importing expensive drugs and limits the exorbitant cost spent on expensive chemical drugs.
- the compounds used in this invention are based on green or phyto synthesis and have very few side effects compared to synthetic and chemical compounds, and also have less toxic properties compared to synthetic and chemical types.
- Medicinal and cosmetic formulations used in this invention are environmentally friendly and biodegradable, and their effects are mild and non-aggressive.
- the herbal composition produced will increase the effect of other cosmetic creams in improving patients with skin diseases and repairing the epidermis layer and rejuvenating the skin.
- the production process of this invention in the industrial phase is as follows:
- the guide for employing the invention in one of the industrial applications is as follows:
- medicinal compounds in the form of creams, ointments, gels, serums, tonics, lotions, toners, detergents, cleansers, scrubs, masks and etc.
- Table1 Examining exosomes using DLS (Dynamic Light Scattering) method: The diameter of the particles in the suspension containing the isolated exosomes was determined using the VASCO3 model DLS device. The results of the DLS charts show that more than 80% of the extracted vesicles are less than 100 nm in size, which indicates the presence of the extracted exosomes in the examined plant species, algae and medicinal mushrooms.
- DLS Dynamic Light Scattering
- Table 2 Investigating the toxic properties of extracted exosomes and their survival rate by MTT assay method on epidermal cells of the skin of mice treated with medicinal compounds containing exosome.
- Table 4 Quantitative investigation of gene expression of Collagen I, Collagen III, Homo sapiens prolyl 4-hydroxylase subunit alpha 1 and Elastin genes using Realtime PCR test: NC in control and treated mice
- This invention can be exploited in the pharmaceutical-medical industry (cancer and viral diseases) as an effective medicine to cure a variety of skin diseases, including eczema, blemishes & melasma, skin sagging & aging, cellular regeneration of human skin and enhancing the water content or moisture of the skin, preventing skin peeling, improving skin thickness, increasing skin elasticity, removing skin moles, removing skin pimples, improving skin texture, reducing the size of skin pores, increasing skin smoothness, improving skin aging spots, burn spots, improving skin color and improving the appearance of wounds and healing wounds in diabetic people.
- skin diseases including eczema, blemishes & melasma, skin sagging & aging, cellular regeneration of human skin and enhancing the water content or moisture of the skin, preventing skin peeling, improving skin thickness, increasing skin elasticity, removing skin moles, removing skin pimples, improving skin texture, reducing the size of skin pores, increasing skin smooth
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Abstract
L'invention concerne des produits médicinaux à base d'exosomes végétaux, d'algues, et de champignons médicinaux pour traiter des maladies de la peau qui sont des composés bénéfiques, et qui ont été sélectionnés à partir d'extraits et d'essences des familles de plantes visées conformément à la maladie ciblée. Ils sont fabriqués avec des exosomes purifiés à partir des plantes énumérées ci-dessus, d'algues spiruline et de champignons shiitake. Les exosomes dérivés de plantes ont une structure similaire aux exosomes isolés à partir de mammifères et agissent en tant que messagers extracellulaires dans une communication intercellulaire. De plus, ces vésicules sont capables de transférer des ARNm, des microARN (miARN), des lipides bioactifs et des protéines à des cellules humaines et animales.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IB2022/060893 WO2023089462A1 (fr) | 2022-11-13 | 2022-11-13 | Produits médicinaux à base d'exosomes dérivés de plantes, d'humains, d'algues, et de champignons médicinaux pour traiter des maladies de la peau |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IB2022/060893 WO2023089462A1 (fr) | 2022-11-13 | 2022-11-13 | Produits médicinaux à base d'exosomes dérivés de plantes, d'humains, d'algues, et de champignons médicinaux pour traiter des maladies de la peau |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023089462A1 true WO2023089462A1 (fr) | 2023-05-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2022/060893 Ceased WO2023089462A1 (fr) | 2022-11-13 | 2022-11-13 | Produits médicinaux à base d'exosomes dérivés de plantes, d'humains, d'algues, et de champignons médicinaux pour traiter des maladies de la peau |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2023089462A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2025070726A1 (fr) * | 2023-09-29 | 2025-04-03 | ロート製薬株式会社 | Composition pour maintenir ou augmenter la protéine structurelle fibreuse |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170209365A1 (en) * | 2014-11-07 | 2017-07-27 | Exostemtech Co., Ltd. | Cosmetic Composition Containing Exosomes Extracted from Stem Cell for Skin Whitening, Antiwrinkle or Regeneration |
| WO2019027387A2 (fr) * | 2017-02-01 | 2019-02-07 | Yedi̇tepe Üni̇versi̇tesi̇ | Produit contenant des exosomes d'origine végétale |
-
2022
- 2022-11-13 WO PCT/IB2022/060893 patent/WO2023089462A1/fr not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170209365A1 (en) * | 2014-11-07 | 2017-07-27 | Exostemtech Co., Ltd. | Cosmetic Composition Containing Exosomes Extracted from Stem Cell for Skin Whitening, Antiwrinkle or Regeneration |
| WO2019027387A2 (fr) * | 2017-02-01 | 2019-02-07 | Yedi̇tepe Üni̇versi̇tesi̇ | Produit contenant des exosomes d'origine végétale |
Non-Patent Citations (1)
| Title |
|---|
| SHI HUI, WANG MIN, SUN YAOXIANG, YANG DAKAI, XU WENRONG, QIAN HUI: "Exosomes: Emerging Cell-Free Based Therapeutics in Dermatologic Diseases", FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, vol. 9, XP093069463, DOI: 10.3389/fcell.2021.736022 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2025070726A1 (fr) * | 2023-09-29 | 2025-04-03 | ロート製薬株式会社 | Composition pour maintenir ou augmenter la protéine structurelle fibreuse |
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