Process for synthesizing a formulation of galangin-loaded hydrogel for expedited wound healing

{
  "publication_number": "US2026102371A1",
  "country": "US",
  "kind": "A1",
  "title": "Process for synthesizing a formulation of galangin-loaded hydrogel for expedited wound healing",
  "abstract": "The present invention relates to a process for synthesizing a formulation of Galangin (GAL)-loaded hydrogel for Expedite wound healing. The formulation is prepared by mixing 5 gm GAL and 1.5 g of HPMC, wherein at room temperature, HPMC was dispersed in 100 ml of distilled water with stirring by a hotplate stirrer (LMS-1003), and the previously weighed GAL was gradually dissolved in the mixture with continuous stirring for 10 minutes. Beakers were then sealed with parafilm, stored at 4° C. for two days prior to utilization. This invention investigated the potential effects of galangin (GAL), on wound healing in streptozotocin-induced diabetic rats. The findings demonstrate that GAL is a promising topical agent for promoting diabetic wound healing through antioxidant, anti-inflammatory, pro-angiogenic, and pro-collagen activities.",
  "claims": [
    "1. A method for synthesizing a Galangin-loaded hydrogel formulation, the method comprising: weighing 5 g of Galangin (GAL) and 1.5 g of hydroxypropyl methyl cellulose (HPMC) using an analytical balance comprising a RADWAG AS 110/X configured for ±0.1 mg resolution; dispersing the 1.5 g of HPMC in 100 mL distilled water at room temperature while continuously agitating using a magnetic hotplate stirrer comprising an LMS-1003 device; gradually introducing the 5 g of GAL into the stirred HPMC dispersion and maintaining shear mixing for 10 minutes; sealing the mixture in a container with parafilm; and storing the sealed mixture at 4° C. for two days to permit complete hydrogel swelling and structural stabilization, wherein the step of dispersing the hydroxypropyl methyl cellulose (HPMC) in distilled water comprises initiating polymer hydration by exposing the HPMC powder to a pre-established vortex of the aqueous medium, the vortex being created by the LMS-1003 stirrer operating at a rotational speed between 350 and 600 rpm, and wherein the polymer hydration is controlled such that the HPMC particles undergo sequential wetting, boundary-layer dissolution, and chain disentanglement, thereby generating a progressively thickening colloidal matrix in which the hydroxyl-substituted cellulose chains expand through hydrogen bonding with the aqueous phase while avoiding lump formation through maintenance of constant shear gradients across the depth of the vessel, and wherein the step of gradually dissolving the Galangin (GAL) into the hydrated HPMC matrix further comprises controlling the solute introduction rate such that each increment of GAL is added only upon reaching a predetermined optical turbidity threshold indicative of polymer-solute intercalation, wherein such intercalation involves non-covalent interaction between the polyphenolic structure of GAL and the ether-substituted anhydroglucose units of HPMC, and wherein the GAL introduction is carried out in aliquots of 0.25-0.50 g at intervals of 15-25 seconds to maintain uniform solute dispersion and prevent localized crystallization or agglomeration during the shear-induced solubilization phase. 2. The method of claim 1, wherein the shear mixing for 10 minutes comprises maintaining a controlled laminar-to-transitional flow regime within the hydrogel precursor solution, the flow regime being defined by a Reynolds number between 1800 and 2300 for the selected vessel geometry, such that the hydrodynamic forces generated by the stirrer enable the GAL molecules to undergo homogeneous distribution across the HPMC polymeric network while simultaneously promoting partial alignment of HPMC molecular chains, thereby facilitating uniform spatial encapsulation of GAL within the hydrogel structure prior to the cold-swelling step. 3. The method of claim 1, wherein the sealing step using parafilm comprises applying a multi-layered, stretch-sealed polymeric membrane around the opening of the container, the membrane being tensioned to generate an airtight closure capable of restricting vapor permeability to below 10 g·m −2 ·day −1 at ambient pressure, thereby inhibiting moisture loss and preventing atmospheric carbon dioxide or environmental particulates from contacting the hydrogel precursor during the swelling period, and wherein the parafilm sealing further provides a static barrier that maintains the pressure equilibrium of the headspace above the hydrogel mixture. 4. The method of claim 1, wherein the storing of the sealed container at 4° C. for two days comprises maintaining the hydrogel precursor under a temperature-controlled environment in which the thermal gradient across the vessel does not exceed ±0.3° C., and wherein the reduced temperature induces contraction of the HPMC polymer chains followed by gradual re-expansion as water molecules migrate into amorphous polymer domains, thereby forming a three-dimensional gel network whose pore size distribution remains within a micro-scale range dictated by the degree of hydration achieved during the cold-swelling period, and wherein the distilled water used for HPMC dispersion is first subjected to a degassing step comprising vacuum extraction at <20 kPa for 5-10 minutes to remove dissolved gases that would otherwise cause microbubble retention within the hydrogel matrix during polymer swelling, and wherein the degassed water is subsequently equilibrated to room temperature prior to polymer hydration to ensure consistent diffusion coefficients for both water and GAL during dissolution. 5. The method of claim 1, wherein the GAL is introduced into the HPMC dispersion under illumination conditions restricted to <200 lux to prevent photochemical alteration of the GAL molecular structure, and wherein the GAL powder is pre-sieved using a stainless-steel mesh of 100-150 μm pore size to ensure granulometric homogeneity during incorporation into the polymer matrix, thereby ensuring consistent dissolution kinetics across all GAL particles during mixing, and wherein the container in which the GAL-HPMC mixture is sealed comprises a borosilicate glass vessel having a thermal expansion coefficient below 4×10 −6 /° C., the vessel being selected to ensure that no micro-structural deformation occurs during the two-day cold-swelling phase at 4° C., and wherein the interior surface roughness of the vessel is restricted to <0.4 μm Ra to prevent surface-induced aggregation of GAL or non-uniform HPMC hydration near the vessel walls. 6. The method of claim 1, wherein the hydrogel mixture is stored under static conditions, and wherein the static placement includes isolation from vibrational sources exceeding 0.1 g acceleration to prevent mechanical disruption of the hydration-driven network formation occurring within the HPMC matrix, such that the polymer chains undergo uninterrupted hydration, swelling, and entanglement as water molecules diffuse into the inter-chain regions to form the final hydrogel configuration, and wherein the HPMC used in the hydrogel formulation is selected to comprise a hydroxypropoxy substitution degree (DS) between 0.1 and 0.25 and a methoxy substitution degree (MS) between 1.1 and 1.7, and wherein these substitution levels govern the hydration behavior of the polymer during the two-day swelling step at 4° C. such that the resultant hydrogel exhibits a micro-porous network architecture with diffusion characteristics determined by the chemical modification pattern of the cellulose backbone. 7. The method of claim 1, wherein the step of mixing GAL into the HPMC dispersion further comprises controlling the pH of the aqueous medium within 6.0-7.0 to maintain GAL in a non-ionized state, and wherein the pH control is achieved through monitoring using a glass-electrode pH meter configured to ±0.01 pH accuracy without introduction of any additional buffering agents not disclosed in the formulation, and wherein following the two-day swelling period at 4° C., the hydrogel is equilibrated at room temperature for a period of 30-45 minutes while remaining sealed under parafilm, the equilibration step enabling thermal relaxation of polymer chain conformations without exposure to ambient humidity fluctuations that would otherwise affect the stability of the hydrated hydrogel network. 8. The method of claim 1, wherein the introducing of GAL into the hydrated HPMC dispersion further comprises performing continuous rotational shear mixing such that the shear field generated within the vessel produces both radial and axial flow components, wherein the stirrer's magnetic coupling induces alternating torque fluctuations that facilitate disruption of micro-aggregates of GAL, and wherein the GAL-containing dispersion is maintained at a temperature between 22° C. and 26° C. during the mixing interval to avoid viscosity shifts in the polymer matrix that would otherwise alter the solute mobility profile and impede uniform solvation of GAL's polyphenolic structure, and wherein the GAL added to the hydrogel precursor is pre-conditioned by storing the GAL in a desiccated chamber maintained below 10% relative humidity for at least 12 hours prior to weighing, such that the moisture content of the GAL powder remains below 0.5% w/w, thereby ensuring predictability of dissolution kinetics upon contact with the aqueous HPMC medium and preventing hydration-induced clumping during the staged solute incorporation step. 9. The method of claim 1, wherein the HPMC dispersion undergoes a pre-hydration rest phase lasting 2-4 minutes immediately after initial polymer wetting and before GAL is introduced, the pre-hydration phase permitting partial unraveling of the cellulose ether chains, such that the polymer viscosity profile transitions toward a pseudo-plastic state, thereby allowing the subsequently introduced GAL molecules to interdigitate with the expanding polymeric network rather than lodging within partially hydrated polymer aggregates. 10. The method of claim 1, wherein the magnetic stirring performed by the LMS-1003 apparatus is executed using a PTFE-coated magnetic stir bar configured with an aspect ratio between 3:1 and 4:1, the geometry of the stir bar being selected to generate elongated vortical flow paths along the longitudinal axis of the mixing vessel such that the hydrogel precursor experiences periodic shear cycling that enhances homogeneity of GAL distribution within the matrix prior to cold storage, and wherein the distilled water used for preparing the hydrogel precursor is characterized by electrical conductivity not exceeding 2 μS/cm, and wherein the water is filtered prior to use through a 0.22 μm membrane filter to remove particulate contaminants that would otherwise act as nucleation points for localized HPMC aggregation or GAL precipitation during the 10-minute shear mixing stage. 11. The method of claim 1, wherein during the two-day cold-swelling period at 4° C., the sealed container is positioned such that the hydrogel precursor occupies between 40% and 70% of the container volume, thereby creating a defined headspace above the hydrogel mixture, the headspace functioning to stabilize hydrogel development by enabling pressure equilibration while preventing any compressive resistance that might alter the hydration patterns of the HPMC molecular chains during the slow-temperature swelling progression, and wherein the sealed vessel is placed upon a vibration-dampening platform during the two-day storage period, the platform comprising a viscoelastic composite capable of attenuating oscillatory energy above 5 Hz, thereby ensuring that the hydrogel precursor remains undisturbed in a static spatial configuration essential for the uniform inward diffusion of water molecules into the polymer microdomains of the HPMC matrix. 12. The method of claim 1, wherein the final hydrogel mixture is subjected to visual inspection using a diffuse white-light source of 5600 K color temperature immediately following removal from cold storage, the inspection being performed while the parafilm seal remains intact, such that the operator evaluates internal phase uniformity through optical transmission and scattering characteristics without exposing the hydrogel matrix to ambient humidity exchange, and wherein the environmental conditions during the entire preparation procedure are controlled such that ambient relative humidity remains between 30% and 55%, and wherein no airflow exceeding 0.15 m/s is permitted across the open container during polymer hydration and GAL mixing steps, thereby preventing premature surface skin formation on the hydrogel precursor and ensuring consistent solvent evaporation rates during the active mixing interval. 13. The method of claim 1, wherein the hydrogel precursor is mixed within a vessel comprising cylindrical walls having a diameter-to-height ratio between 1:1 and 1:1.6, the vessel geometry being chosen to generate a stable, centrally aligned vortex during shear mixing, thereby ensuring consistent distribution of kinetic energy across the depth of the solution, uniform dissolution of GAL throughout the polymer matrix, and symmetric hydration of HPMC chains prior to the cold-swelling phase, and wherein the gradual incorporation of Galangin (GAL) into the HPMC dispersion further comprises maintaining the centerline temperature of the dispersion within ±0.5° C. of ambient temperature by periodically monitoring the thermal profile with a Class A glass laboratory thermometer, and wherein the temperature stabilization is performed to prevent thermally induced viscosity fluctuations within the polymeric medium, such that the GAL molecules experience a consistent microviscosity environment during solvation and interpenetration into the hydrating HPMC chain network throughout the entire 10-minute mixing interval. 14. The method of claim 1, wherein the hydrogel precursor is mixed in a vessel that has undergone a pre-conditioning step comprising rinsing with 70% ethanol, drying under laminar airflow, and subsequently equilibrating the vessel for at least 10 minutes to eliminate volatile residues, and wherein said pre-conditioning step is performed to ensure that the internal surface chemistry of the vessel remains inert with respect to GAL adsorption or polymer-surface interactions that may otherwise disrupt uniform matrix formation during HPMC hydration. 15. The method of claim 1, wherein the stirring operation is carried out at a rotational speed selected such that the vortex depth remains between 20% and 35% of the liquid column height, the vortex geometry enabling partitioning of the fluid into a high-shear central zone and a low-shear peripheral zone, and wherein GAL particles introduced into the vortex are entrained into the high-shear region for rapid dissolution before being advected toward the low-shear region, thereby producing cyclical solute redistribution within the hydrating HPMC matrix during mixing, and wherein the two-day cold storage at 4° C. is conducted inside a refrigeration system equipped with forced-air circulation restricted to an airflow velocity below 0.05 m/s at the shelf level, and wherein the hydrogel container is positioned at least 5 cm away from the refrigeration air outlets, thereby ensuring uniform cooling of the hydrogel precursor and preventing localized convective cooling patterns from influencing the polymer chain hydration symmetry across the entire bulk volume. 16. The method of claim 1, wherein the container sealed with parafilm is placed in an upright orientation during the cold-swelling phase, the upright positioning ensuring a gravitationally stable hydrogel-air interface, and wherein the hydrogel precursor is allowed to undergo unidirectional vertical hydration expansion from bottom to top, such that hydration gradients remain minimal due to the absence of lateral fluid displacement forces that would otherwise arise if the container were tilted or horizontally oriented during the swelling period."
  ],
  "cpc": [
    "A61K 31/352",
    "A61K 47/38",
    "A61K 9/06",
    "A61P 17/02"
  ],
  "filing_date": "2025-12-08",
  "publication_date": "2026-04-16",
  "application_number": "US-202519412201-A"
}