KR-102962663-B1 - Composition comprising pH sensitive lipid nanoparticles which comprises cationic material

Abstract

The present invention relates to pH-sensitive nanoparticles containing a cationic substance that can stably encapsulate an active substance in a high content and has an excellently enhanced skin retention and delivery effect of the active ingredient when applied to the skin, and to a composition containing the same.

Inventors

• 한상덕
• 강민경
• 현승민
• 이승원
• 박효영

Assignees

• 동아제약 주식회사

Dates

Publication Date

20260508

Application Date

20221223

Claims (16)

1. pH-sensitive lipid nanoparticles comprising a cationic substance, lipids, and an active ingredient, wherein the active ingredient is in a form encapsulated by the cationic substance and lipids, The above cationic substance is one or more naturally derived cationic substances selected from the group consisting of cetearyl betainate mesylate, arachidyl/behenyl betainate essylate, and stearyl/behenyl betainate mesylate; and One or more selected from the group consisting of one or more synthetic cationic substances selected from the group consisting of distearoylethyl hydroxyethylmonium methosulfate and amodimethicone; The content of the cationic substance in the above pH-sensitive lipid nanoparticles is 0.1 to 2 weight% with respect to the total weight of the lipid nanoparticles; pH-sensitive lipid nanoparticles, wherein the lipid is a combination of cetyl palmitate and an oil selected from cocoglyceride, sunflower seed oil, caprylic/capric triglyceride, olive oil and octyldodecanol.
2. pH-sensitive lipid nanoparticles according to claim 1, wherein the cationic substance exhibits lipophilicity.
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6. pH-sensitive lipid nanoparticles according to claim 1, wherein the lipid content in the lipid nanoparticles is 0.1 to 30 weight% with respect to the total weight of the lipid nanoparticles.
7. pH-sensitive lipid nanoparticles according to claim 1, wherein the active ingredient is one or more selected from the group consisting of retinoid substances such as tretinoin, retin-al, retinol, retinyl palmitate, retinyl retinoate, or hydroxypinacolone retinoate; pharmaceutically acceptable salts of heparin such as heparin or sodium heparin; taurine; ubiquinone; hydroxydecyl ubiquinone; tocopherol; tocopherol acetate; niacinamide; adenosine; ascorbic acid and derivatives thereof.
8. pH-sensitive lipid nanoparticles according to claim 1, wherein the content of the active ingredient in the lipid nanoparticles is 0.01 to 10 weight% with respect to the total weight of the lipid nanoparticles.
9. pH-sensitive lipid nanoparticles according to claim 1, wherein the lipid nanoparticles exhibit a zeta potential of 20 to 60 mV.
10. pH-sensitive lipid nanoparticles according to claim 1, further comprising one or more auxiliary lipids selected from the group consisting of phosphatidylcholine, ceramide NP, ceramide AP, cholesterol, and cetearyl alcohol.
11. pH-sensitive lipid nanoparticles according to claim 1, wherein the content of auxiliary lipid in the lipid nanoparticles is 0.01 to 3 weight% with respect to the total weight of the lipid nanoparticles.
12. pH-sensitive lipid nanoparticles according to claim 1, further comprising one or more emulsifiers selected from the group consisting of glyceryl-based, oliveate-based, polyglyceryl-10 laurate, and polyglyceryl-3 alkylglucose distearate.
13. In claim 1, the pH-sensitive lipid nanoparticles have a particle size of 50 to 200 nm.
14. A pharmaceutical composition for preventing, improving, or treating skin aging, wrinkles, and skin sensitivity, comprising pH-sensitive lipid nanoparticles according to claim 1.
15. A cosmetic composition comprising pH-sensitive lipid nanoparticles according to claim 1.
16. a) A step of weighing water, an aqueous solvent, and an aqueous component as the aqueous phase, and a cationic substance and an auxiliary lipid as the oil phase, respectively, and then heating to dissolve them; b) A step of adding an active ingredient to the above oil phase and dissolving it; c) a step of adding the aqueous phase of step a) to the oil phase of step b) and stirring to emulsify; d) A step of filtering the emulsified reaction product of step c), adjusting the temperature, and introducing it into a microfluidizer to perform high-pressure emulsification; e) includes a step of cooling the reaction product that has been high-pressure emulsified in step d) above, and The above cationic substance is one or more naturally derived cationic substances selected from the group consisting of cetearyl betainate mesylate, arachidyl/behenyl betainate essylate, and stearyl/behenyl betainate mesylate, and One or more selected from the group consisting of one or more synthetic cationic substances selected from the group consisting of distearoylethyl hydroxyethylmonium methosulfate and amodimethicone; The content of the above cationic substance is 0.1 to 2 weight% with respect to the total weight of the lipid nanoparticles being manufactured; A method for preparing pH-sensitive lipid nanoparticles according to claim 1, wherein the lipid is cetyl palmitate; and a combination of oils selected from cocoglycerides, sunflower seed oil, caprylic/capric triglycerides, olive oil, and octyldodecanol.

Description

Composition comprising pH-sensitive lipid nanoparticles which comprise cationic material The present invention relates to pH-sensitive nanoparticles containing a cationic substance and a composition containing the same. More specifically, the invention relates to pH-sensitive nanoparticles containing a cationic substance and a composition containing the same, which can stably encapsulate an active substance at a high content and have an excellently enhanced skin retention and delivery effect of the active ingredient when applied to the skin. In the fields of cosmetics and pharmaceuticals, there has long been a demand for the development of formulations capable of stably encapsulating various substances beneficial to the skin to effectively improve its condition. However, many bioactive substances are poorly soluble or unstable in aqueous phases, often binding to or reacting with other substances to destabilize the entire system. To overcome this, technologies utilizing emulsion particles of nanometer to micrometer size to more stably and easily encapsulate active substances within formulations have been recognized as core technologies. Representative examples include nanoemulsions, which are formed by preparing a semi-formulation using surfactants with specific hydrophilic-hydrophobic ratios and then treating it with a high-pressure emulsifier to create fine emulsion particles; and liposomes, which are spherical or other shaped particle structures manufactured using phospholipid raw materials derived from plants or animals to encapsulate active substances while forming single or multiple membranes. In addition, technologies for manufacturing nano-sized emulsion particles using microemulsions formed by three phases consisting of an emulsifier, oil, and water at optimal concentrations have been reported. These emulsion particles present a problem in that the active ingredients within the emulsion are continuously exposed to water, leading to degradation due to oxidation or decomposition. Furthermore, emulsion films are physically and chemically very weak and unstable; they are susceptible to destruction by contamination from salts or charged organic or inorganic substances. Additionally, because they are highly vulnerable to heat and light, they have the disadvantage of being unstable during long-term storage. Furthermore, keratin—a hard, brick-like support composed of dead cells that constitute the main component of the stratum corneum—and intercellular lipids, which bind this support like cement, play various roles in physiological protective barriers, such as maintaining skin moisture and protecting it from external harmful factors; however, for topical agents used in the cosmetics and pharmaceutical industries, they can be considered a major obstacle to the transdermal absorption of drugs. It is generally known in the industry that delivering drugs through keratin is impossible due to its excessively rigid structure. Therefore, there is a high demand for delivery vehicles capable of effectively delivering and penetrating active substances into the skin and retaining them within the skin in sufficient quantities. Figure 1 is a diagram showing the results of a stability confirmation test of pH-sensitive lipid nanoparticles according to the present invention. Figures 2 and 3 show the results of a zeta potential verification test of pH-sensitive lipid nanoparticles according to the present invention. Figures 4 and 5 are diagrams showing the test results confirming the skin permeability of pH-sensitive lipid nanoparticles according to the present invention. Figure 6 is a diagram showing the test results confirming the skin retention amount of pH-sensitive lipid nanoparticles according to the present invention. Figure 7 is a diagram showing the test results confirming the change in zeta potential according to pH of pH-sensitive lipid nanoparticles according to the present invention. The present invention will be described in detail below. In one embodiment, the present invention relates to pH-sensitive lipid nanoparticles comprising a cationic substance, lipids, and an active ingredient. The present invention is characterized by including a unique cationic lipid material to achieve a high encapsulation rate of the active ingredient, stability of lipid nanoparticles, and skin penetration, permeability, and retention of the active ingredient. As a specific embodiment, the cationic material used in the present invention may be a naturally derived cationic material or a synthetic cationic material. Preferably, the cationic material used in the present invention may be a lipophilic surfactant that is insoluble in water. Since the core of the pH-sensitive lipid nanoparticle composition according to the present invention, formed by this lipophilic surfactant, is lipid, it may be desirable to use a surfactant with high compatibility with lipids to secure stable cationic particles. The naturally derived cationic substan