Nano-starch and nano-starch / ester suspensions, and iodinated nano-starch and nano-starch / ester suspensions
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- I2PURE CORP
- Filing Date
- 2025-09-03
- Publication Date
- 2026-05-21
AI Technical Summary
Existing methods for preparing nano-starch suspensions are limited by their suitability for intended uses, often requiring acidic or alkaline environments, surfactants, and generating wastewater, which degrade the utility of nano-starch particles and limit their stability, especially under basic conditions.
A novel preparation method for nano-starch and nano-starch/ester suspensions that are aqueous-based, avoiding acidic or alkaline hydrolysis, surfactants, and wastewater generation, and utilizing fewer steps to create stable nano-starch suspensions that can be iodinated for improved stability and mechanical properties.
The method produces nano-starch suspensions with enhanced stability, particularly under basic conditions, allowing for longer-term molecular iodine stability and improved mechanical properties, suitable for applications such as wound healing and bone void fillers.
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Figure US2025044754_21052026_PF_FP_ABST
Abstract
Description
PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00NANO-STARCH SUSPENSIONS, NANO-STARCH / ESTER SUSPENSIONS, IODINATED NANO-STARCH SUSPENSIONS, IODINATED NANO-STARCH / ESTER SUSPENSIONS, NANO-STARCH PRODUCTS AND IODINATED NANO-STARCH PRODUCTS, METHOD FOR PREPARING SAME AND USING SAMECROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application claims the benefit of U.S. Provisional Patent Application Numbers 63 / 690,301, filed September 3, 2024, and 63 / 795,097, filed April 25, 2025, which are incorporated by reference herein in their entirety.BACKGROUND
[0002] Novel methods of preparing nano-starch or nano-starch / ester suspensions are disclosed in this application. The obtained nano-starch suspensions and nano-starch / ester suspensions showed unexpectedly high stabilities and can be iodinated using various iodine solutions to provide iodinated nano-starch suspensions and nano-starch / ester suspensions that have long-term stabilities and improved stabilities under basic conditions. New products can be prepared using the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and / or nano- starch / ester suspensions and used for applications as disclosed herein.SUMMARY
[0003] One aspect of the present disclosure relates to methods for preparing nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano- starch / ester suspensions, unless specified otherwise, all suspensions are aqueous suspensions. The nano-starch suspensions and the nano-starch / ester suspensions disclosed in this application are also referred to SAMI (Starch Amylase Microparticle) suspensions. In certain embodiments, the SAMI suspensions can be iodinated to provide and the iodinated nano-starch suspensions and iodinated nano-starch / ester suspensions prepared, together referred to as h-SAMI suspensions.-1-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0004] Another aspect of the present disclosure relates to the nano-starch suspensions, nano- starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano-starch / ester suspensions prepared according to the methods disclosed herein.
[0005] Another aspect of the present disclosure relates to nano-starch products and iodinated nano-starch products prepared using the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and / or iodinated nano-starch / ester suspensions.
[0006] Another aspect of the present disclosure relates to uses of the iodinated nano-starch suspensions, iodinated nano-starch / ester suspensions, and iodinated nano-starch products.BRIEF DESCRIPTION OF THE DRAWINGS
[0007] Figure 1 shows viscosity and temperature evolution of corn starch-glycerin (1 : 12 by weight) mixtures as a function of microwave heating time at 1,250 W in 2.2 cubic feet. The temperature was the temperature of the oven wall, which can be higher than that of the mixtures. For example, some mixtures had a temperature of 160 °C when the oven wall temperature was 180 °C.
[0008] Figures 2(a)-(b) show outgassing of I2 from a piece of porcine skin applied with a test sample (5,000 ppm molecular iodine dispersion in propylene glycol). Figure 2(a): Inverted vial with porcine skin attached underneath the cap. Figure 2(b): Iodine diffusion in the DMPD solutions at different time intervals.
[0009] Figure 3 shows iodine flux comparisons of multiple test samples (10k ppm molecular iodine): a commercial povidone iodine solution (10k ppm molecular iodine, circle), an iodine solution in propylene glycol (10k ppm molecular iodine, square), an iodine solution in glycerin (10k ppm molecular iodine, triangle), as well as the fortified nano-starch suspension described in Example 15 (10k ppm molecular iodine, diamond).
[0010] Figures 4(a)-4(b) show antibiotic effects of examples of iodinated calcium hemi-hydrate beads or bone void fillers prepared in Example 16, photograph was taken after 96 hours of incubation at 37 °C. Figure 4(a): Calcium hemi-hydrate beads or bone void fillers made with calcium hemi sulfate (18 g) and 4 wt.% nano-starch suspension (0.5% iodine, 15 g), wherein iodine was introduced during the mixing and setting of the plaster. Figure 4(b): Calcium hemi-hydrate beads or bone void fillers made with calcium hemi sulfate (18 g) and 4 wt.% nano-starch suspension with no iodine (15-2-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 g), and then upon setting the calcium hemi-hydrate beads or bone void fillers were soaked in a 20,000 ppm propylene glycol molecular iodine solution for 30 seconds. Percent nano-starch in the calcium hemi-hydrate beads or bone void fillers was 3.3% by weight.
[0011] Figure 5 shows the amount of available molecular iodine in the test solutions under basic conditions: PVPI solution diluted with McKesson irrigation solution (solid triangle) and a nano- starch suspension (solid circle), and BD Surgiphor™ antimicrobial irrigation system (solid diamond).
[0012] Figure 6 shows changes in the concentration of free L in the oil phase against dilution ratio of various commercial iodophor / iodine products (Example 17).
[0013] Figure 7 shows mean (N=6) amount of molecular iodine released in mg / L or ppm from each iodophor sample as a function of total titratable iodine in each dilution level of various commercial iodophor / iodine products (Example 17).
[0014] Figure 8 shows amount of iodine released in mg / L or ppm from various commercial iodophor samples as a function of the total titratable iodine in each sample when heptane (the lipophilic phase) was saturated with 50 wt.% soybean lecithin (Example 17).DETAILED DESCRIPTION
[0015] Established methods to prepare nano-starch particles often include processes that may limit suitability of the nano-starch particles for intended uses. Examples of such processes include, without limitation, acid hydrolysis, precipitation with solvents, milling, gamma radiation, electrospraying, high-pressure homogenization, ultrasonic processing with or without acid hydrolysis, and enzymatic partial degradation with or without acid hydrolysis. Methods including different processes would embody different processing constraints and yield materials that have distinct properties. For instance, the use of alkaline or acidic environments or incorporation of surfactants can degrade the utility of the resulting nano-starch particles for potential applications.
[0016] Disclosed herein are novel preparation methods with fewer steps for preparation of nano-starch suspensions comprising starch-containing nano-particles and nano-starch / ester suspensions comprising starch / ester-containing nano-particles. The nano-starch suspensions and the nano-starch / ester suspensions disclosed in this application are also referred to SAMI (Starch Amylase Microparticle) suspensions. In certain embodiments, the SAMI suspensions can be iodinated to-3-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 provide and the iodinated nano-starch suspensions and iodinated nano-starch / ester suspensions prepared, together referred to as h-SAMI suspensions.
[0017] SAMI suspensions and I2-SAMI suspensions as disclosed herein are novel carriers that can replace aqueous carriers (e.g., water, aqueous solutions, and aqueous suspensions, water miscible solutions, water miscible suspensions, and mixtures thereof) in preparation of various products with improved mechanical property (e.g., see Example 16, bone void fillers), and improved molecular iodine stability for products comprising molecular iodine. Molecular iodine in b-SAMI showed good long-term stability of molecular iodine (e.g., Example 14). Iodinated nano-starch products prepared using SAMI suspensions showed unexpectedly higher long-term stability of molecular iodine and significantly higher stability under basic conditions when compared with the same products prepared using an aqueous carrier. See, e.g., Example 13 for comparison of PVPI solutions diluted with an embodiment of the SAMI suspension and aqueous carriers (e.g., water and saline). Many antibiotics lose efficacy between pH 7.4 to 9. However, pH of bioburden in chronic wounds can be around 9 or higher. The unexpected higher stability of molecular iodine in iodinated nano-starch products under basic conditions would be beneficial for various uses, e.g., without limitation, wound healings.
[0018] Unless otherwise specified, the term “about” before a numerical value means + / - 10% of the numerical value.I. PREPARATION METHODS FOR NANO-STARCH SUSPENSIONS, NANO- STARCH / ESTER SUSPENSIONS, IODINATED NANO-STARCH SUSPENSIONS, AND IODINATED NANO-STARCH / ESTER SUSPENSIONS.
[0019] One aspect of the present disclosure relates to methods for preparing nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano- starch / ester suspensions. Unless specified otherwise, all suspensions are aqueous suspensions.
[0020] The novel preparation methods disclosed herein involve fewer steps than prior art methods and are more cost efficient and environmentally friendly. For example, the preparation methods disclosed herein do not include acidic or alkaline starch hydrolysis that are time and energy consuming and generate wastewater. The preparation methods disclosed herein do not require surfactants or dispersants to stabilize nano-starch particles in aqueous solution. Finally, the preparation methods disclosed herein can be readily adopted for bulk production.-4-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0021] The preparation methods described herein can be applicable for various types of starch. In certain embodiments, the starch is a plant-based starch or a modified starch that is derived from a plant-based starch. In certain embodiments, the starch contains about 20 wt% to about 30 wt% amylose. In certain embodiments, the starch contains about 70 wt% to about 80 wt% amylopectin. In certain embodiments, the starch contains about 1 wt% amylose to about 70% amylose. In certain embodiments, the starch is a waxy starch that contains less than about 1 wt% amylose. In certain embodiments, the starch is a high amylose starch that contains more than about 70% amylose. In certain embodiments, the starch is derived from potato, corn, maize, tapioca, rice, wheat, pea, barley, banana, or any mixtures thereof. Examples of various starch can be found in Robyt J. (2008). Starch: Structure, Properties, Chemistry, and Enzymology. In: Fraser-Reid, B.O., Tatsuta, K., Thiem, J., (eds) Glycoscience. Springer, Berlin, Heidelberg, pp. 1437-72.
[0022] In certain embodiments, the starch concentration of the nano-starch suspension, nano- starch / ester suspension, iodinated nano-starch suspension, or iodinated nano-starch / ester suspension is about 0.3 wt% to about 5 wt%, about 0.3 wt% to about 4 wt%, about 0.3 wt% to about 2 wt%, about 0.5 wt% to about 1.5 wt%, about 1 wt% to about 1.5 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9 wt%, or about 4.0 wt%.A. Preparation methods for nano-starch suspensions.
[0023] The preparation methods disclosed herein for nano-starch suspension provide nano- starch particles that stabilize molecular iodine at neutral pH levels.
[0024] In certain embodiments, the method for preparing a nano-starch suspension comprises:-5-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 a) heating a first mixture comprising glycerin and starch to form a first composition having a first viscosity, the water content of the first mixture is no more than about 10 wt%; and b) adding water to the first composition to create a nano-starch suspension.
[0025] In certain embodiments, the water content in the first mixture is about 1 wt% to about 10 wt%, about 1 wt% to about 5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt%.
[0026] In certain embodiments, the method further comprises reducing water content in the starch and / or glycerin before mixing the glycerin and starch to provide the first mixture. For example, without limitation, the starch may be heated to a temperature ranging from about 50 °C to about 200 °C, about 55 °C to about 200 °C, about 60 °C to about 200 °C, about 65 °C to about 200 °C, about 70 °C to about 200 °C, about 75 °C to about 200 °C, about 80 °C to about 200 °C, about 85 °C to about 200 °C, about 90 °C to about 200 °C, about 95 °C to about 200 °C, about 100 °C to about 200 °C, about 105 °C to about 200 °C, about 110 °C to about 200 °C, about 115 °C to about 200 °C, about 120 °C to about 200 °C, about 125 °C to about 200 °C, about 130 °C to about 200 °C, about 135 °C to about 200 °C, about 140 °C to about 200 °C, about 145 °C to about 200 °C, about 150 °C to about 200 °C, about 155 °C to about 200 °C, about 160 °C to about 200 °C, about 165 °C to about 200 °C, about 170 °C to about 200 °C, about 175 °C to about 200 °C, about 180 °C to about 200 °C, about 185 °C to about 200 °C, about 190 °C to about 200 °C, about 195 °C to about 200 °C, about 50 °C to about 150 °C, about 55 °C to about 150 °C, about 60 °C to about 150 °C, about 65 °C to about 150 °C, about 70 °C to about 150 °C, about 75 °C to about 150 °C, about 80 °C to about 150 °C, about 85 °C to about 150 °C, about 90 °C to about 150 °C, about 95 °C to about 150 °C, about 100 °C to about 150 °C, about 105 °C to about 150 °C, about 110 °C to about 150 °C, about 115 °C to about 150 °C, about 120 °C to about 150 °C, about 125 °C to about 150 °C, about 130 °C to about 150 °C, about 135 °C to about 150 °C, about 140 °C to about 150 °C, about 145 °C to about 150 °C, about 50 °C to about 100 °C, about 55 °C to about 100 °C, about 60 °C to about 100 °C, about 65 °C to about 100 °C, about 70 °C to about 100 °C, about 75 °C to about 100 °C, about 80 °C to about 100 °C, about 85 °C to about 100 °C, about 90 °C to about 100 °C, about 95 °C to about 100 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, about 80 °C, about 85 °C, about 90 °C, about 95 °C, about 100 °C, about 105 °C, about 110 °C, about 115 °C, about 120 °C, about 125 °C, about-6-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00130 °C, about 135 °C, about 140 °C, about 145 °C, about 150 °C, about 155 °C, about 160 °C, about 165 °C, about 170 °C, about 175 °C, about 180 °C, about 185 °C, about 190 °C, about 195 °C, or about 200 °C to reduce water content. In certain embodiments, the starch is heated to the temperature set forth supra for about 1 min to about 20 min, about 1 min, about 2 min, about 3 min, about 4 min, about 5 min, about 6 min, about 7 min, about 8 min, about 9 min, about 10 min, about 11 min, about 12 min, about 13 min, about 14 min, about 15 min, about 16 min, about 17 min, about 18 min, about 19 min, or about 20 min.
[0027] In certain embodiments, the method further comprises adding ammonium sulfate to the glycerin to reduce water content.
[0028] In certain embodiments, the first viscosity is about 5 to about 6 times of the viscosity of pure glycerin. In certain embodiments, the first viscosity is about 4,200 cp to about 6,600 cp.
[0029] In certain embodiments, heating the first mixture comprises heating the first mixture to a first temperature of about 140 °C to about 190 °C, about 150 °C to about 190 °C, about 160 °C to about 190 °C, about 170 °C to about 190 °C, about 180 °C to about 190 °C, about 140 °C to about 180 °C, about 140 °C to about 170 °C, about 140 °C to about 160 °C, about 140 °C to about 150 °C, about 150 °C to about 180 °C, about 160 °C to about 180 °C, about 170 °C to about 180 °C, about 150 °C to about 170 °C, about 150 °C to about 160 °C, about 160 °C to about 180 °C, about 170 °C to about 180 °C, about 160 °C to about 170 °C, about 140 °C, about 145 °C, about 150 °C, about 155 °C, about 160 °C, about 165 °C, about 170 °C, about 175 °C, about 180 °C, about 185 °C, or about 190 °C. In certain embodiments, the first mixture is maintained at the first temperature for about 5 second to about 5 min, about 5 second, about 10 second, about 15 second, about 20 second, about 25 second, about 30 second, about 35 second, about 40 second, about 45 second, about 50 second, about 55 second, about 60 second, about 65 second, about 70 second, about 75 second, about 80 second, about 85 second, about 90 second, about 95 second, about 100 second, about 105 second, about 110 second, about 115 second, about 2 min, about 3 min, about 4 min, or about 5 min.
[0030] In certain embodiments, the first composition and the nano-starch suspension of step b) has a second temperature of about 40 °C to about 100 °C, about 45 °C to about 100 °C, about 50 °C to about 100 °C, about 55 °C to about 100 °C, about 60 °C to about 100 °C, about 65 °C to about 100 °C, about 70 °C to about 100 °C, about 75 °C to about 100 °C, about 80 °C to about 100 °C, about 85 °C to about 100 °C, about 90 °C to about 100 °C, about 95 °C to about 100 °C, about 40 °C to about-7-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO0095 °C, about 45 °C to about 95 °C, about 50 °C to about 95 °C, about 55 °C to about 95 °C, about 60 °C to about 95 °C, about 65 °C to about 95 °C, about 70 °C to about 95 °C, about 75 °C to about 95 °C, about 80 °C to about 95 °C, about 85 °C to about 95 °C, about 90 °C to about 95 °C, about 40 °C to about 90 °C, about 45 °C to about 90 °C, about 50 °C to about 90 °C, about 55 °C to about 90 °C, about 60 °C to about 90 °C, about 65 °C to about 90 °C, about 70 °C to about 90 °C, about 75 °C to about 90 °C, about 80 °C to about 90 °C, about 85 °C to about 90 °C, about 40 °C to about 85 °C, about 45 °C to about 85 °C, about 50 °C to about 85 °C, about 55 °C to about 85 °C, about 60 °C to about 85 °C, about 65 °C to about 85 °C, about 70 °C to about 85 °C, about 75 °C to about 85 °C, about 80 °C to about 85 °C, about 40 °C to about 80 °C, about 45 °C to about 80 °C, about 50 °C to about 80 °C, about 55 °C to about 80 °C, about 60 °C to about 80 °C, about 65 °C to about 80 °C, about 70 °C to about 80 °C, about 75 °C to about 80 °C, about 40 °C to about 75 °C, about 45 °C to about 75 °C, about 50 °C to about 75 °C, about 55 °C to about 75 °C, about 60 °C to about 75 °C, about 65 °C to about 75 °C, about 70 °C to about 75 °C, about 40 °C to about 70 °C, about 45 °C to about 70 °C, about 50 °C to about 70 °C, about 55 °C to about 70 °C, about 60 °C to about 70 °C, about 65 °C to about 70 °C, about 40 °C to about 65 °C, about 45 °C to about 65 °C, about 50 °C to about 65 °C, about 55 °C to about 65 °C, about 60 °C to about 65 °C, about 40 °C to about 60 °C, about 45 °C to about 60 °C, about 50 °C to about 60 °C, about 55 °C to about 60 °C, about 40 °C to about 55 °C, about 45 °C to about 55 °C, about 50 °C to about 55 °C, about 40 °C to about 50 °C, about 45 °C to about 50 °C, about 40 °C to about 45 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, about 80 °C, about 85 °C, about 90 °C, or about 95 °C.
[0031] In certain embodiments, the mixture of water and the first composition is homogenized at the second temperature to create the nano-starch suspension.
[0032] In certain embodiments, the ratio of starch to glycerol by weight in the first mixture is about 5 to about 20, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, or about 20.
[0033] In certain embodiments, the ratio of starch to water is about 0.3: 100 to about 4:100, about 1 : 100 to about 1.5:100, about 0.3: 100, about 0.5: 100, about 1 : 100, about 1.5:100, about 2:100, about 2.5: 100, about 3:100, about 3.5:100, or about 4:100.-8-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0034] In certain embodiments, the ratio of water added to starch by weight is about 85, about 86, about 87, about 88, about 89, about 90, about 91, about 92, about 93, about 94, about 95, about 96, about 97, about 98, about 99, or about 100.
[0035] In certain embodiments, the first mixture further comprises one or more additives selected from the group consisting of one or more salts, one or more glycol additives, and any mixtures thereof.
[0036] In certain embodiments, the one or more salts are sodium salts, potassium salts, or mixtures thereof. Examples of the sodium and potassium salts include, without limitation, Nal, KI, NaCl, KC1, and sodium and / or potassium salts of organic acids (e.g., without limitation, Rochelle salt).
[0037] In certain embodiments, the weight of starch to the total weight of the one or more salts is about 1 :0.3 to about 1 :3, 1:0.3 to about 1:2.5, 1 :0.3 to about 1 :2, about 1 :0.3 to about 1 :1.5, about 1:0.3, about 1:0.4, about 1:0.5, about 1 :0.6, about 1 :0.7, about 1 :0.8, about 1 :0.9, about 1 :1, about 1: 1.1, about 1 : 1.2, about 1 :1.3, about 1 :1.4, or about 1: 1.5.
[0038] In certain embodiments, the particle size of the nano-starch particles in the nano-starch suspension prepared from the first mixture containing the one or more salts is smaller than the nano- starch particles in the nano-starch suspension obtained from the same first mixture but without salt or glycol additive. In certain embodiments, the particle size reduction is about 20% to about 50 %.
[0039] In certain embodiments, the mixture of water and the first composition is homogenized using ultrasonic energy, and the nano-starch suspension prepared from the first mixture containing the one or more salts requires a shorter homogenization time than the nano-starch suspension obtained from the same first mixture but without salt or glycol additive. In certain embodiments, the homogenization time reduction is about 50% to about 82.5%.
[0040] Examples of the one or more glycol additives include, without limitation, PEG (e.g., without limitation, PEG200, PEG400), propylene glycol, and mixtures thereof.
[0041] In certain embodiments, the ratio of the starch to the total weight of glycol additives is about 1 to about 1:2.5.-9-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0042] In certain embodiments, the mixture of water and the first composition is homogenized using ultrasonic energy, and the nano-starch suspension prepared from the first mixture containing the one or more glycol additives requires a shorter homogenization time than the nano-starch suspension obtained from the same first mixture but without salt or glycol additive. In certain embodiments, the homogenization time reduction is about 50% to about 75%.
[0043] In certain embodiments, the weight ratio of starch to glycerol to water is 1 : 12:87.
[0044] In certain embodiments, the weight ratio of starch to the total salt(s) to glycerol to water is 1 : 1 : 12:86.
[0045] In certain embodiments, the weight ratio of starch to the total glycol additive(s) to glycerol to water is 1 : 1: 12:86.
[0046] In certain embodiments, the nano-starch suspension prepared from the method disclosed herein has an average particle size of about 100 nm or smaller, about 20 nm to about 100 nm, about 20 nm to about 90 nm, about 20 nm to about 80 nm, about 20 nm to about 70 nm, about 20 nm to about 60 nm, about 20 nm to about 50 nm, about 20 nm to about 40 nm, about 20 nm to about 30 nm, about 20 nm to about 25 nm, about 20 nm, about 21 nm, about 22 nm, about 23 nm, about 24 nm, about 25 nm, about 26 nm, about 27 nm, about 28 nm, about 29 nm, about 30 nm, about 31 nm, about 32 nm, about 33 nm, about 34 nm, about 35 nm, about 36 nm, about 37 nm, about 38 nm, about 39 nm, about 40 nm, about 41 nm, about 42 nm, about 43 nm, about 44 nm, about 45 nm, about 46 nm, about 47 nm, about 48 nm, about 49 nm, about 50 nm, about 51 nm, about 52 nm, about 53 nm, about 54 nm, about 55 nm, about 56 nm, about 57 nm, about 58 nm, about 59 nm, about 60 nm, about 61 nm, about 62 nm, about 63 nm, about 64 nm, about 65 nm, about 66 nm, about 67 nm, about 68 nm, about 69 nm, about 70 nm, about 71 nm, about 72 nm, about 73 nm, about 74 nm, about 75 nm, about 76 nm, about 77 nm, about 78 nm, about 79 nm, about 80 nm, about 81 nm, about 82 nm, about 83 nm, about 84 nm, about 85 nm, about 86 nm, about 87 nm, about 88 nm, about 89 nm, about 90 nm, about 91 nm, about 92 nm, about 93 nm, about 94 nm, about 95 nm, about 96 nm, about 97 nm, about 98 nm, about 99 nm, or about 100 nm.
[0047] In certain embodiments, the nano-starch suspension prepared from the first mixture containing no salt or glycol additive has an average particle size about 40 nm to about 100 nm, about 40 nm to about 90 nm, about 40 nm to about 87 nm, about 40 nm to about 80 nm, about 40 nm to-10-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 about 60 nm, about 40 nm to about 50 nm, about 40 nm to about 45 nm, about 40 nm, about 42 nm, about 55 nm, or about 87 nm.
[0048] In certain embodiments, the nano-starch suspension prepared from the first mixture containing a salt has an average particle size of about 20 nm to about 70 nm, about 20 nm to about 60 nm, about 23 nm to about 50 nm, about 23 nm, about 24 nm, about 25 nm, about 30 nm, about 32 nm, about 35 nm, about 42 nm, about 43 nm, about 45 nm, or about 50 nm.
[0049] In certain embodiments, the nano-starch suspension prepared from the first mixture containing a glycol additive has an average particle size of about 70 nm or less.B. Preparation methods for nano-starch / ester suspensions.
[0050] In certain embodiments, the method for preparing a nano-starch / ester suspension comprises: a) mixing a starch with an organic acid to provide a starch-acid mixture; b) heating a second mixture comprising the starch-acid mixture and a glycol to form a second composition having a second viscosity, the water content of the second mixture is no more than about 10 wt%; and c) adding water to the second composition to create a nano-starch / ester suspension.
[0051] In certain embodiments, the glycol is glycerol, a PEG that is a liquid at room temperature or has a melting point lower than the heating temperature of step 2), or a mixture thereof. Examples of PEG include, without limitation, PEG200 to PEG600, PEG200, PEG400, PEG600, and PEG1500. When a mixture of glycerol and PEG is used, the weight ratio of glycerol EEG can be about 1 :0.1 to about 1 :0.8.
[0052] Examples of the organic acid include, without limitation, lactic acid (LA), acetic acid, or a mixture thereof.
[0053] In certain embodiments, the mixing of step 1) is at RT.
[0054] In certain embodiments, the ratio of starch to the total weight of acid is about 1 to about10. In certain embodiments, the acid is a mixture of LA and acetic acid. The ratio of LA and acetic acid is about 1 : 1.-11-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0055] In certain embodiments, the water content in the second mixture is about 1 wt% to about 10 wt%, about 1 wt% to about 5 wt%, about 1 wt%, about 2 wt%, about 3 wt%, about 4 wt%, about 5 wt%, about 6 wt%, about 7 wt%, about 8 wt%, about 9 wt%, or about 10 wt%. In certain embodiments, the method further comprises reducing water content in the second mixture similar to the water reduction methods described supra, e.g., without limitation, by heating starch, and adding ammonium sulfate to the glycol.
[0056] In certain embodiments, the second viscosity is the same as described supra with respect to the first viscosity.
[0057] In certain embodiments, heating the second mixture comprises heating the second mixture to a third temperature the same as described supra with respect to the first temperature. In certain embodiments, the second mixture is maintained at the third temperature for about 5 second to about 5 min, about 5 second, about 10 second, about 15 second, about 20 second, about 25 second, about 30 second, about 35 second, about 40 second, about 45 second, about 50 second, about 55 second, about 60 second, about 65 second, about 70 second, about 75 second, about 80 second, about 85 second, about 90 second, about 95 second, about 100 second, about 105 second, about 110 second, about 115 second, about 2 min, about 3 min, about 4 min, or about 5 min.
[0058] In certain embodiments, the second composition and the nano-starch / ester suspension of step 2) has a fourth temperature the same as described supra with respect to the second temperature.
[0059] In certain embodiments, the mixture of water and the second composition is homogenized at the fourth temperature to create the nano-starch / ester suspension.
[0060] In certain embodiments, the glycol is glycerol, and the ratio of starch to glycerol by weight in the second mixture is about 5 to about 20, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, or about 20.
[0061] In certain embodiments, the glycol is PEG, and the ratio of starch to PEG by weight is about 1 to about 1: 10, and the second mixture further comprises one of more salts as disclosed herein, e g., without limitation, sodium salts, potassium salts, or a mixture thereof as disclosed herein.
[0062] In certain embodiments, the ratio of starch to water is about 0.3: 100 to about 4:100, about 1 : 100 to about 1.5:100, about 0.3: 100, about 0.5: 100, about 1 : 100, about 1.5:100, about 2:100, about 2.5: 100, about 3:100, about 3.5: 100, or about 4:100.-12-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0063] In certain embodiments, the ratio of water added to starch by weight is about 85, about 86, about 87, about 88, about 89, about 90, about 91, about 92, about 93, about 94, about 95, about 96, about 97, about 98, about 99, or about 100.
[0064] In certain embodiments, the second mixture further comprises one or more additives selected from the group consisting of one or more salts, one or more glycol additives, and any mixtures thereof.
[0065] In certain embodiments, the one or more salts are sodium salts, potassium salts, or mixtures thereof. Examples of the sodium and potassium salts include, without limitation, Nal, KI, NaCl, KC1, and sodium and / or potassium salts of organic acids (e.g., without limitation, Rochelle salt).
[0066] In certain embodiments, the weight of starch to the total weight of the one or more salts is about 1 :0.3 to about 1 :3, 1:0.3 to about 1:2.5, 1 :0.3 to about 1 :2, 1:0.3 to about 1: 1.5, about 1:0.3, about 1 :0.4, about 1 :0.5, about 1 :0.6, about 1 :0.7, about 1 :0.8, about 1 :0.9, about 1:1, about 1: 1.1, about 1 : 1.2, about 1 :1.3, about 1: 1.4, or about 1 : 1.5.
[0067] In certain embodiments, the particle size of the nano-starch / ester particles in the nanostarch suspension prepared from the second mixture containing the one or more salts is smaller than the nano-starch particles in the nano-starch / ester suspension obtained from the same second mixture but without salt or glycol additive. In certain embodiments, the particle size reduction is about 20% to about 50 %.
[0068] In certain embodiments, the mixture of water and the second composition is homogenized using ultrasonic energy, and the nano-starch / ester suspension prepared from the second mixture containing the one or more salts requires a shorter homogenization time than the nano- starch / ester suspension obtained from the same second mixture but without salt or glycol additive. In certain embodiments, the homogenization time reduction is about 50% to about 82.5%.
[0069] Examples of the one or more glycol additives include, without limitation, PEG (e.g., without limitation, PEG200, PEG400), propylene glycol, and mixtures thereof.
[0070] In certain embodiments, the ratio of the starch to the total weight of glycol additives is about 1 to about 1:2.5.-13-183539184.2PCT / US25 / 4475403 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0071] In certain embodiments, the mixture of water and the second composition is homogenized using ultrasonic energy, and the nano-starch / ester suspension prepared from the second mixture containing the one or more glycol additives requires a shorter homogenization time than the nano-starch / ester suspension obtained from the second mixture but without salt or glycol additive.
[0072] In certain embodiments, the weight ratio of starch:glycerin:LA:salt is about l:(8~10): 1: 1 to about 1 :(8~10): 10: 10, about 1:8: 1:1, about 1:9: 1:1, about 1:10:1:1, about 1:8:2:2, about 1:9:2:2, about 1:10:2:2, about 1:8:3:3, about 1:9:33, about 1:10:3:3, about 1:8:4:4, about 1:9:4:4, about 1:10:4:4, about 1:8:5:5, about 1:9:5:5, about 1:10:5:5, about 1:8:6:6, about 1:9:6:6, about 1:10:6:6, about 1:8:7:7, about 1:9:7:7, about 1:10:7:7, about 18:8:8, about 1:9:8:8, about 1:10:8:8, about 1:8:9:9, about 1 :9:9:9, about 1:10:9:9, about 1:8:10:10, about 1:9:10:10, or about 1:10:10:10.
[0073] In certain embodiments, the weight ratio of starch:glycerin:LA is about 1 :(8~10): 1 to about l:(8~10):10, about 1:8:1, about 1:9:1, about 1:10:1, about 1:8:2, about 1:9:2, about 1:10:2, about 1:8:3, about 1:9:3, about 1:10:3, about 1:8:4, about 1:9:4, about 1:10:4, about 1:8:5, about 1:9:5, about 1:10:5, about 1:8:6, about 1:9:6, about 1:10:6, about 1:8:7, about 1:9:7, about 1:10:7, about 1:8:8, about 1:9:8, about 1:10:8, about 1:8:9, about 1:9:9, about 1:10:9, about 1:8:10, about 1:9:10, or about 1:10:10.
[0074] In certain embodiments, the weight ratio of starch:glycerol:LA:AcOH:salt is about l:(8~10): 1:1:1 to about l:(8~10): 10: 10:10, about 1:8:1 :1:1, about 1:9:1 :1:1, about 1:10:1:1:1, about 1:8:2:2:2, about 1:9:2:2:2, about 1:10:2:2:2, about 1 :8:3:3:3, about 1.9333, about 1:10:3:3:3, about1:8:4:4:4, about 1:9:4:4:4, about 1:10:4:4:4, about 1 :8:5:5:5, about 1 :9:5:5:5, about 1:10:5:5:5, about1 :8:6:6:6, about 1 :9:6:6:6, about 1:10:6:6:6, about 1 :8:7:7:7, about 1 :9:7:7:7, about 1:10:7:7:7, about1 :8:8:8:8, about 1 :9:8:8:8, about 1:10:8:8:8, about 1 :8:9:9:9, about 1:99:9:9, about 1:10:9:9:9, about1:8:10:10:10, about 1:9:10:10:10, or about 1:10:10:10:10..
[0075] In certain embodiments, the weight ratio of starch:glycerin:LA:AcOH is about l:(8~10): 1: 1 to about 1 :(8~10): 10: 10, about 1:8: 1:1, about 1:9: 1:1, about 1:10:1:1, about 1:8:2:2, about 1:9:2:2, about 1:10:2:2, about 1:8:3:3, about 1:9:33, about 1:10:3:3, about 1:8:4:4, about 1:9:4:4, about 1:10:4:4, about 1:8:5:5, about 1:9:5:5, about 1:10:5:5, about 1:8:6:6, about 1:9:6:6, about 1:10:6:6, about 1:8:7:7, about 1:9:7:7, about 1:10:7:7, about 18:8:8, about 1:9:8:8, about-14-183539184.2PCT / US25 / 4475403 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO001:10:8:8, about 1:8:9:9, about 1 :9:9:9, about 1:10:9:9, about 1:8:10:10, about 1:9:10:10, or about 1:10:10:10.
[0076] In certain embodiments, the weight ratio of starch:glycerin:AcOH:salt is about l:(8~10): 1: 1 to about 1 :(8~10): 10: 10, about 1:8: 1:1, about 1:9: 1:1, about 1:10:1:1, about 1:8:2:2, about 1:9:2:2, about 1:10:2:2, about 1:8:3:3, about 1:9:3:3, about 1:10:3:3, about 1:8:4:4, about 1:9:4:4, about 1:10:4:4, about 1:8:5:5, about 1:9:5:5, about 1:10:5:5, about 1:8:6:6, about 1:9:6:6, about 1:10:6:6, about 1:8:7:7, about 1:9:7:7, about 1:10:7:7, about 18:8:8, about 1:9:8:8, about 1:10:8:8, about 1:8:9:9, about 1.999, about 1:10:9:9, about 1:8:10:10, about 1:9:10:10, or about 1:10:10:10.
[0077] In certain embodiments, the weight ratio of starch: glycerin :AcOH is about 1 :(8~10): 1 to about 1 :(8~10): 10, about 1:8:1, about 1:9:1, about 1:10:1, about 1:8:2, about 1:9:2, about 1:10:2, about 1:8:3, about 1:9:3, about 1:10:3, about 1:8:4, about 1:9:4, about 1:10:4, about 1:8:5, about 1:9:5, about 1:10:5, about 1:8:6, about 1:9:6, about 1:10:6, about 1:8:7, about 1:9:7, about 1:10:7, about 1:8:8, about 1:9:8, about 1:10:8, about 1:8:9, about 1:9:9, about 1:10:9, about 1:8:10, about 1:9:10, or about 1:10:10.
[0078] In certain embodiments, the weight ratio of starch:PEG:LA:salt is about 1 : 1 : 1 : 1 to about 1:1:2:1.
[0079] In certain embodiments, the nano-starch / ester suspension prepared from the method disclosed herein has an average particle size of about 100 nm or smaller, about 20 nm to about 100 nm, about 20 nm to about 90 nm, about 20 nm to about 80 nm, about 20 nm to about 70 nm, about 20 nm to about 60 nm, about 20 nm to about 50 nm, about 20 nm to about 40 nm, about 20 nm to about 30 nm, about 20 nm to about 25 nm, about 20 nm, about 21 nm, about 22 nm, about 23 nm, about 24 nm, about 25 nm, about 26 nm, about 27 nm, about 28 nm, about 29 nm, about 30 nm, about 31 nm, about 32 nm, about 33 nm, about 34 nm, about 35 nm, about 36 nm, about 37 nm, about 38 nm, about 39 nm, about 40 nm, about 41 nm, about 42 nm, about 43 nm, about 44 nm, about 45 nm, about 46 nm, about 47 nm, about 48 nm, about 49 nm, about 50 nm, about 51 nm, about 52 nm, about 53 nm, about 54 nm, about 55 nm, about 56 nm, about 57 nm, about 58 nm, about 59 nm, about 60 nm, about 61 nm, about 62 nm, about 63 nm, about 64 nm, about 65 nm, about 66 nm, about 67 nm, about 68 nm, about 69 nm, about 70 nm, about 71 nm, about 72 nm, about 73 nm, about 74 nm, about 75 nm, about 76 nm, about 77 nm, about 78 nm, about 79 nm, about 80 nm, about 81 nm, about 82 nm, about-15-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO0083 nm, about 84 nm, about 85 nm, about 86 nm, about 87 nm, about 88 nm, about 89 nm, about 90 nm, about 91 nm, about 92 nm, about 93 nm, about 94 nm, about 95 nm, about 96 nm, about 97 nm, about 98 nm, about 99 nm, or about 100 nm.
[0080] In certain embodiments, the nano-starch / ester suspension prepared from the second mixture containing no salt or glycol additive has an average particle size of about 100 nm to about 90 nm, about 100 nm, or about 90 nm.
[0081] In certain embodiments, the nano-starch / ester suspension prepared from the second mixture containing a salt has an average particle size of about 70 nm or less.
[0082] In certain embodiments, the nano-starch / ester suspension prepared from the second mixture containing a glycol additive has an average particle size of about 70 nm or less.
[0083] Another aspect of the present disclosure relates to the nano-starch suspensions, nano- starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano-starch / ester suspensions prepared according to the methods disclosed herein. Another aspect of the present disclosure relates to uses of the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano-starch / ester suspensions.C. Preparation methods for iodinated nano-starch suspensions and iodinated nano- starch / ester suspensions.
[0084] In certain embodiments, the method for preparing an iodinated nano-starch suspension or an iodinated nano-star / ester suspension comprises:A) preparing a nano-starch suspension or a nano-starch / ester suspension as disclosed herein; andB) adding an iodination agent into the nano-starch suspension or nano-starch / ester suspension to form an iodinated nano-starch suspension or iodinated nano-starch / ester suspension.
[0085] Examples of the iodination agent include, without limitation, solid molecular iodine, molecular iodine solutions in one or more water-miscible solvents, and aqueous molecular iodine solutions.-16-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0086] In certain embodiments, the iodination agent is solid molecular iodine, the method further comprises adding one or more additional iodide salts as disclosed herein to the nano-starch suspension or nano-starch / ester suspension to reach a final iodide concentration or about 3 wt% to about 4 wt%.
[0087] Examples of molecular iodine solution in one or more water-miscible solvents may have a concentration of molecular iodine of about 0.1 wt% to about 15 wt%, about 1 wt% to about 15 wt%, about 0.1 wt% to about 20 wt%, or about 1 wt% to about 20 wt%. Examples of water-miscible solvents include, without limitation, alcohol (e.g., without limitation, ethanol, isopropanol), acetone, DMSO, glycerin, propylene glycol, or a mixture thereof. See W02023 / 019033 for more examples of molecular iodine solutions in water-miscible solvents, which are incorporated herein by reference.
[0088] Examples of aqueous solution of molecular iodine include, without limitation, a Lugol’s iodine solution in water, and a PVPI solution (e.g., without limitation, buffered to be pH 4.5) containing 1% titratable iodine. In one example, a lugol solution (20k PPM I2)used to iodinate a nano-starch suspension was prepared by dissolving KI (3.5 g) and 12 (2 g) in water (94.5 g).
[0089] In certain embodiments, the method for preparing an iodinated nano-starch suspension or an iodinated nano-star / ester suspension comprises:A) preparing the first composition or the second composition as disclosed herein; andB) adding an aqueous solution of molecular iodine (e.g., without limitation, an aqueous solution of molecular iodine comprising a lugol’s iodine solution or a PVPI solution) to the first composition to create an iodinated nano-starch suspension or to the second composition to form an iodinated nano-starch / ester suspension, similar to the method as disclosed herein of adding water to the first or second composition to create the nano-starch suspension or nano- starch / ester suspension.
[0090] In certain embodiments, the aqueous solution of molecular iodine further comprises one or more molecular iodine solution in one or more water-miscible solvents as disclosed herein.II. NANO-STARCH SUSPENSIONS, NANO-STARCH / ESTER SUSPENSIONS, IODINATED NANO-STARCH SUSPENSIONS, AND IODINATED NANO- STARCH / ESTER SUSPENSIONS.-17-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0091] Another aspect of the present disclosure relates to the nano-starch suspensions, nano- starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano-starch / ester suspensions prepared according to the methods disclosed herein.
[0092] In certain embodiments, the starch concentration of the nano-starch suspension, nano- starch / ester suspension, iodinated nano-starch suspension, or iodinated nano-starch / ester suspension is about 0.3 wt% to about 5 wt%, about 0.3 wt% to about 4 wt%, about 0.3 wt% to about 2 wt%, about 0.5 wt% to about 1.5 wt%, about 1 wt% to about 1.5 wt%, about 0.3 wt%, about 0.4 wt%, about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9 wt%, or about 4.0 wt%.
[0093] In certain embodiments, the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano-starch / ester suspensions prepared according to the methods disclosed herein has an average particle size of about 100 nm or smaller, about 20 nm to about 100 nm, about 20 nm to about 90 nm, about 20 nm to about 80 nm, about 20 nm to about 70 nm, about 20 nm to about 60 nm, about 20 nm to about 50 nm, about 20 nm to about 40 nm, about 20 nm to about 30 nm, about 20 nm to about 25 nm, about 20 nm, about 21 nm, about 22 nm, about 23 nm, about 24 nm, about 25 nm, about 26 nm, about 27 nm, about 28 nm, about 29 nm, about 30 nm, about 31 nm, about 32 nm, about 33 nm, about 34 nm, about 35 nm, about 36 nm, about 37 nm, about 38 nm, about 39 nm, about 40 nm, about 41 nm, about 42 nm, about 43 nm, about 44 nm, about 45 nm, about 46 nm, about 47 nm, about 48 nm, about 49 nm, about 50 nm, about 51 nm, about 52 nm, about 53 nm, about 54 nm, about 55 nm, about 56 nm, about 57 nm, about 58 nm, about 59 nm, about 60 nm, about 61 nm, about 62 nm, about 63 nm, about 64 nm, about 65 nm, about 66 nm, about 67 nm, about 68 nm, about 69 nm, about 70 nm, about 71 nm, about 72 nm, about 73 nm, about 74 nm, about 75 nm, about 76 nm, about 77 nm, about 78 nm, about 79 nm, about 80 nm, about 81 nm, about 82 nm, about 83 nm, about 84 nm, about 85 nm, about 86 nm, about 87 nm, about 88 nm, about 89 nm, about 90 nm, about 91 nm, about 92 nm, about 93 nm, about 94 nm, about 95 nm, about 96 nm, about 97 nm, about 98 nm, about 99 nm, or about 100 nm.-18-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0094] In certain embodiments, the nano-starch suspension, nano-starch / ester suspension, iodinated nano-starch suspension, or iodinated nano-starch / ester suspension prepared according to the methods disclosed herein shows no sedimentation for over three months at RT. In certain embodiments, the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano-starch / ester suspensions have a starch concentration of about 0.3 wt% to about 2 wt%, about 0.3 wt% to about 1.5 wt%, about 0.5 wt% to about 2 wt%, about 0.5 wt% to about 1.5 wt%, about 1 wt% to about 2 wt%, or about 1 wt% to about 1.5 wt%.
[0095] In certain embodiments, the nano-starch suspension, nano-starch / ester suspension, iodinated nano-starch suspension, or iodinated nano-starch / ester suspension prepared according to the methods disclosed shows sedimentation after 1 day at RT. In certain embodiments, the nano- starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and iodinated nano-starch / ester suspensions have a starch concentration of 4 wt%.
[0096] In certain embodiments, the iodinated nano-starch suspension, or iodinated nano- starch / ester suspension prepared according to the methods disclosed herein shows at least a one-year shelf stability at room temperature. In certain embodiments, the iodine concentration is about 300 ppm, or about 500 ppm. In certain embodiments, the starch concentration is about 1 wt%. In certain embodiments, the glycerin concentration is about 10 wt%. In certain embodiments, the salt concentration is about 1 wt%.III. NANO-STARCH PRODUCTS PREPARED USING NANO-STARCH SUSPENSIONS, AND / OR NANO-STARCH / ESTER SUSPENSIONS DISCLOSED HEREIN.
[0097] Another aspect of the present disclosure relates to nano-starch products prepared using the nano-starch suspensions, and / or nano-starch / ester suspensions prepared according to the methods disclosed herein.
[0098] In certain embodiments, the nano-starch product is prepared by replacing part or all of one or more aqueous carriers (e.g., without limitation, water, aqueous solution or suspension, and / or water miscible solution / suspension) usually used for preparation of the product with the nano-starch suspension and / or nano-starch / ester suspensions disclosed herein.-19-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0099] In certain embodiments, the aqueous solution or suspension to be replaced is at a neutral pH. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 7. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 6 to about 7.A. Nano-starch fillers
[0100] In certain embodiments, the nano-starch product is a nano-starch filler comprising calcium hemi-hydrate (e.g., without limitation, nano-starch bone beads or bone void fillers) prepared by a method comprising mixing calcium hemihydrate with the nano-starch suspension disclosed herein, and forming the nano-starch fillers (e.g., without limitation, nano-starch bone beads or bone void fillers). Also disclosed herein is a method for using the nano-starch fillers (e.g., without limitation, nano-starch bone beads or bone void fillers).
[0101] In certain embodiments, the mixing ratio of nano-starch suspension to calcium hemihydrate is about 1.3 to about 2 by weight.
[0102] In certain embodiments, the nano-starch suspension has a starch concentration of about 1 wt% to about 4 wt%.
[0103] In certain embodiments, the starch concentration of the dry calcium hemi-hydrate beads or bone void fillers is about 0.5 wt% to about 5 wt%.
[0104] In certain embodiments, the nano-starch bone beads or bone void fillers are formed by setting within about 5 to about 6 minutes at bed side after the mixing step.
[0105] In certain embodiments, the nano-starch bone beads or bone void fillers utilizing a nano- starch suspension have improved compression strength values of the beads or bone void fillers than calcium hemi-hydrate beads or bone void fillers incorporated with starch powder directly at equivalent concentration levels. Examples of comparison data are shown in Table 11.B. Nano-starch injectables.
[0106] In certain embodiments, the nano-starch product is a nano-starch injectable. In certain embodiments, the nano-starch injectable is prepared by replacing part or all of water, aqueous solution or suspension, and / or water miscible solution / suspension in an injectable with the nano-starch suspension and / or nano-starch / ester suspensions disclosed herein.-20-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0107] In certain embodiments, the aqueous solution or suspension to be replaced is at a neutral pH. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 7. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 6 to about 7.IV. IODINATED NANO-STARCH PRODUCTS PREPARED USING NANOSTARCH SUSPENSIONS, NANO-STARCH / ESTER SUSPENSIONS, IODINATED NANO-STARCH SUSPENSIONS, AND / OR IODINATED NANO-STARCH / ESTER SUSPENSIONS DISCLOSED HEREIN.
[0108] Another aspect of the present disclosure relates to iodinated nano-starch products prepared using the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and / or iodinated nano-starch / ester suspensions prepared according to the methods disclosed herein.
[0109] In certain embodiments, the iodinated nano-starch product is prepared by replacing part or all of water, aqueous solution or suspension, and / or water miscible solution / suspension used in preparation of the product with the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, and / or iodinated nano-starch / ester suspensions prepared according to the methods disclosed herein.
[0110] In certain embodiments, the aqueous solution or suspension to be replaced is at a neutral pH. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 7. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 6 to about 7.[OHl] In certain embodiments, the aqueous solution or suspension to be replaced is at an acidic pH. In certain embodiments, the acidic pH is about 4.0 to about 6.0.
[0112] Examples of the iodinated nano-starch products include, without limitation, antisepsis products, hemostatic products, antimicrobial products, scar-reducing products, wound-healing enhancement products, skin care product, and anti-tumor products. In certain embodiments, the iodinated nano-starch products can be used as consumer products, cosmetic products, visualization-21-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 products, agricultural products, surface disinfectants, and / or water disinfectants at least partly due to their antisepsis, hemostatic and / or antimicrobial properties.
[0113] In certain embodiments, provided herein are a kit comprising one or more iodinated nano-starch products disclosed herein. In certain embodiments, the kit is a First aid kit. In certain embodiments, the iodinated nano-starch products are over the counter (OTC) products.
[0114] The iodinated nano-starch products provided herein may be used as antisepsis products, hemostatic products, antimicrobial products, scar-reducing products, wound-healing enhancement products, skin care product, anti -turn or products, consumer products, cosmetic products, and / or visualization products on a subject that is human or non-human (e.g., without limitation, veterinary / pet use or care). Examples of non-human subjects include, without limitation, pets, and livestock.
[0115] In certain embodiments, the iodinated nano-starch products can be used as pet nutraceuticals (e.g., without limitation, water additives), for veterinary and / or pet care (e.g., without limitation, ear cleaning, paw pad treatment, horse rain rot, hoof care). Such iodinated nano-starch products can be the same or substantially the same as the iodinated nano-starch products that are used for human healthcare applications).
[0116] Examples of antisepsis products include, without limitation, skin antisepsis, surgical / wound irrigation, wound soaks, chronic wound care products (e.g., without limitation, products used for treating bed pressure ulcers, diabetic ulcers and sores), bandage soaks / coatings, and hydrogels (e.g., without limitation, for wound care and cosmetic use).
[0117] Examples of hemostatic products include, without limitation, hemostatic liquids, and can also be used as an additive in toothpaste, and wound care products.
[0118] Examples of antimicrobial products include, without limitation, rinses (e.g., without limitation, oral rinse), sprays (e.g., without limitation, nasal spray), drops (e.g., without limitation, eye drops, ear drops), lotions (e.g., without limitation, hand lotion, body lotion), hydrogels, coatings, swabs (e.g., without limitation, ear swabs, nasal swabs), products that can be nebulized, surgical scrub applications (e.g., without limitation, products for healthcare professionals with hand and skin cleaning before and following medical procedures) and injectable products. In certain embodiments, the rinses, sprays, drops, lotions, hydrogels, coatings, and / or swabs, can be administered to any body-22-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 part, tissue, lesion, wound, cavity as needed. In certain embodiments, the rinses, sprays, drops, lotions, hydrogels, coatings and / or swabs, can be applied to an article to be applied to a subject, especially articles that remain contact with and / or in the subject for an extended period. Examples of such articles include, without limitation, catheters, ports, wound treatment and / or care products (e.g., without limitation, gauze, suture, bandage, hydrogels, bone fillers), and surgical products or portions thereof that have contact with the subject.
[0119] In certain embodiments, the products that can be nebulized can be nebulized for a subject to inhale for treating respiratory infections (e.g., without limitation, lung infection).
[0120] In certain embodiments, an injectable product can be injected to an eye of a subject for treating endophthalmitis. In certain embodiments, an injectable product can be injected to a joint of a subject for treating joint infection.
[0121] In certain embodiments, the visualization product can be injected into a joint for joint inflation that provides joint visualization for arthroscopic surgery.
[0122] In certain embodiments, the scar-reducing products can be applied to a wound on a subject to reduce scar formation.
[0123] In certain embodiments, the wound-healing enhancement products can be applied to a wound on a subject to enhance wound healing.
[0124] In certain embodiments, the anti -tumor products can be applied to a subject to prohibit tumor growth. In certain embodiments, the anti-tumor product is an injectable product that can be injected to a tumor of a subject for prohibit growth of the tumor.
[0125] Examples of consumer products include, without limitation, toothpaste, oral rinse, shampoo (e.g., without limitation, dandruff shampoo).
[0126] Examples of cosmetic product include, without limitation, lotions, sprays, hydrogels, masks.
[0127] Examples of agricultural products include, without limitation, produce spray, and produce washing / disinfection products.
[0128] In certain embodiments, the iodinated nano-starch product is an injectable product. For example, an embodiment of the antimicrobial product can be used in surgical applications when-23-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 placed into the body of a subject. Such an antimicrobial product can be a hydrogel product as described herein that has one or more benefits, e.g., without limitation, infection avoidance, infection recovery, hemostatic benefits, and wound healing. In certain embodiments, the injectable product is a cosmetics.
[0129] In certain embodiments, PVPI solution diluted with the nano-starch suspension (e.g., without limitation, about 1 wt% starch) or nano-starch / ester suspension remained stable after 60 days when stored in sealed jars in dark, while the dilution using water showed a rapid loss of molecular iodine in minutes. Surprisingly, PVPI solution diluted with the nano-starch suspension (e.g., without limitation, about 1 wt% starch) or nano-starch / ester suspension showed higher titratable iodine than PVPI solution diluted with water.
[0130] The term “biostatic persistence” means that after the subj ect’ s contact with the iodinated nano-starch suspension, iodinated nano-starch / ester suspension, or iodinated nano-starch product as disclosed herein, the microorganism count at the contact site will be equal to or lower than baseline for a first time period post contact. The term “baseline” means the microorganism count at the site of contact immediately before contact of the iodinated nano-starch suspension, iodinated nano- starch / ester suspension, or iodinated nano-starch product as disclosed herein.
[0131] Unless otherwise specified, the term “biocidal persistence” means that at the subject’s contact site of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension, or iodinated nano-starch product as disclosed herein, wherein the site is subjected to a first microorganism challenge, the microorganism count reduction after a second time period post contact is at least about 1 log lower than the microorganism count at a site of the same microorganism challenge without the contact. The term “biocidal persistence” may be modified by the extent of microorganism reduction and the second time period the “biocidal persistence” lasts. For example, a 3 log / 6 hours biocidal persistence means that at the site of the contact of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension, or iodinated nano-starch product as disclosed herein the microorganism count measured at six hours post contact is reduced by about 3 log compared to the microorganism count at a site of the same microorganism challenge without the contact six hours post challenge. For example, a 2 log / 12 hour biocidal persistence means that at the site of the contact of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension, or iodinated nano-starch product as disclosed herein the microorganism count measured twelve hours-24-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 post contact is reduced by about 2 log lower compared to the microorganism count at a site of the same microorganism challenge without the contact 12 hours later.
[0132] Unless otherwise specified, the term “prolonged biocidal activity” means that at the site of the contact of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension, or iodinated nano-starch product as disclosed herein, wherein the site is subject to the first microorganism challenge and at least a second microorganism challenge during a third time period post contact, the microorganism count measured at the end of the third time period post contact is reduced at least about 1 log compared to the microorganism count at a site subjected to the same microorganism challenges at the end of the third time period. Similarly, the term prolonged biocidal activity may be further defined by the extent of microorganism reduction and the third time period the “prolonged biocidal activity” lasts. For example, a 3 log / 6 hours prolonged biocidal activity means that at the site of the contact of iodinated nano-starch suspension, iodinated nano-starch / ester suspension, or iodinated nano-starch product as disclosed herein, the microorganism count measured six hours post contact is reduced about 3 log compared to the microorganism count at a site of the same microorganism challenges after 6 hours without the contact, wherein other than the first microorganism challenge, at least a second microorganism challenge is imposed within 6 hours post contact. For example, a 2 log / 12 hour prolonged biocidal activity means that at the site of the contact of iodinated nano-starch suspension, iodinated nano-starch / ester suspension or iodinated nano-starch product as disclosed herein, the microorganism count measured 12 hours post contact is reduced about 2 log compared to the microorganism count at a site of the same microorganism challenges after 12 hours without the contact, wherein other than the first microorganism challenge, at least a second microorganism challenge is imposed within 12 hours post contact.
[0133] In certain embodiments, the iodinated nano-starch suspension or iodinated nano- starch / ester suspension can be used for preparing a coating with biostatic persistence, biocidal persistence, and / or prolonged biocidal activity.A. Molecular iodine nano-starch dilution
[0134] In certain embodiments, the iodinated nano-starch product is a molecular iodine nano- starch dilution, prepared by mixing one or more embodiments of the SAMI suspensions and / or one or more embodiments of the L-SAMI suspensions as disclosed herein with a molecular iodine composition that comprises molecular iodine.-25-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0135] In certain embodiments, the molecular iodine composition is an aqueous solution or suspension comprising molecular iodine. The molecular iodine nano-starch dilution can be prepared by mixing the aqueous solution or suspension comprising molecular iodine with one or more embodiments of the SAMI suspension and / or one or more embodiments of the I2-SAMI suspensions as disclosed herein. In certain embodiments, the molecular iodine nano-starch dilution is prepared by mixing an aqueous solution or suspension comprising molecular iodine with an embodiment of the SAMI suspensions disclosed herein, e.g., an embodiment of the nano-starch suspensions, and the nano-starch / ester suspensions. In certain embodiments, the molecular iodine nano-starch dilution is prepared by mixing an aqueous solution or suspension comprising molecular iodine with an embodiment of the I2-SAMI suspensions as disclosed herein, e.g., iodinated nano-starch suspensions, and / or iodinated nano-starch / ester suspensions prepared according to the methods disclosed herein.
[0136] Compositions comprising relatively high concentration of molecular iodine can be diluted with water, aqueous solution, or suspensions before use. In certain embodiments, the water, aqueous solution, or suspensions can be replaced with one or more embodiments of the SAMI suspensions and / or one or more embodiments of the I2-SAMI suspensions as disclosed herein.
[0137] In certain embodiments, the aqueous solution or suspension to be replaced is at a neutral pH. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 7. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 6 to about 7.
[0138] In certain embodiments, the aqueous solution or suspension to be replaced is at an acidic pH. In certain embodiments, the acidic pH is about 4.0 to about 6.0.
[0139] In certain embodiments, the aqueous solution of molecular iodine is a PVPI solution. In certain embodiments, the PVPI solution contains about 1% titratable iodine. In certain embodiments, the PVPI solution has a pH of about 4.5. In certain embodiments, the PVPI solution comprises PVP polymer of 8,000 Da molecular weight. In certain embodiments, the PVPI solution contains about 10% PVP. In certain embodiments, the PVPI solution has a ratio of PVP polymer v. molecular iodine of at least about 10: 1, at least about 9: 1, at least about 8: 1, at least about 7: 1, at least about 6:1, at least about 5: 1, at least about 4: 1, at least about 3: 1, at least about 2:1. In certain embodiments, the molecular iodine nano-starch dilution has a ratio of PVP polymer v. molecular iodine of no more than about 5:1, no more than about 4.5: 1, no more than about 4: 1, no more than-26-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 about 3.5: 1, no more than about 3:1, no more than about 2.5: 1, no more than about 2:1, no more than about 1.5 : 1 , or no more than about 2 : 1.
[0140] In certain embodiments, the molecular iodine nano-starch dilution of the PVPI solution has a titratable iodine of about 5% to about 0.1 %, about 4.5% to about 0.1 %, about 4% to about 0.1 %, about 3.5% to about 0.1 %, about 3% to about 0.1 %, about 2.5% to about 0.1 %, about 2% to about 0.1 %, about 1.5% to about 0.1 %, about 1% to about 0.1 %, or about 0.5% to about 0.1 %.
[0141] In certain embodiments, the aqueous solution of molecular iodine is a Lugol’s iodine solution in water. In certain embodiments, the Lugol’s solution has an iodine concentration of 20k PPM. In certain embodiments, the Lugol’s solution is prepared by dissolving KI (3.5 g) and 12 (2 g) in water (94.5 g).
[0142] In certain embodiments, the molecular iodine nano-starch dilution has a titratable iodine concentration of about 100 ppm to about 5,000 ppm, about 100 ppm to about 4,000 ppm, about 100 ppm to about 3,000 ppm, about 100 ppm to about 1,000 ppm, or about 100 ppm to about 500 ppm. In certain embodiments, the molecular iodine nano-starch dilution has a pH of about 4.0 to about 6.0.
[0143] In certain embodiments, the molecular iodine concentration of the molecular iodine nano-starch dilution has is about 50 ppm to about 100 ppm by weight.
[0144] In certain embodiments, the molecular iodine concentration of the molecular iodine nano-starch dilution does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at room temperature on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year, at least about 1.5 year, at least about 2 years, or at least about 3 years.
[0145] In certain embodiments, the molecular iodine concentration of the molecular iodine nano-starch dilution does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at about 4 °C on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year, at least about 1.5 year, at least about 2 years, or at least about 3 years.
[0146] In certain embodiments, the molecular iodine nano-starch dilution has a shelf-life of at least about 1 year, at least about 1.5 year, at least about 2 years, or at least about 3 years at room temperature.-27-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0147] In certain embodiments, the molecular iodine nano-starch dilution has a shelf-life of at least about 1 year, at least about 1.5 year, at least about 2 years, or at least about 3 years at about 4 °C.
[0148] In certain embodiments, the molecular iodine nano-starch dilution showed better molecular iodine stabilities under basic conditions compared to the dilution of the molecular iodine composition with water, aqueous solution and / or aqueous suspension. As shown in Example 13-11, molecular iodine of the dilution of a PVPI solution with water or aqueous solution (e.g., saline) was consumed in less than 2 min, while the molecular iodine nano-starch dilution of the PVPI solution at the same molecular iodine concentration showed no significant consumption of molecular iodine after at least 99 min.
[0149] In certain embodiments, the molecular iodine concentration of the molecular iodine nano-starch dilution does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% under basic condition for at least about 30 min, at least about 1 hour, at least about 1.5 hours, at least about 2 hours, at least about 2.5 hours, or at least about 3 hours. In certain embodiments, the molecular iodine concentration of the molecular iodine nano-starch dilution does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% under basic condition at room temperature for at least about 30 min, at least about 1 hour, at least about 1.5 hours, at least about 2 hours, at least about 2.5 hours, or at least about 3 hours.B. Iodinated fillers
[0150] In certain embodiments, the iodinated nano-starch suspension can be used to replace water in forming iodinated plaster or resorbable iodinated nano-starch fillers (e.g., without limitation, iodinated nano-starch bone beads or bone void fillers). In certain embodiments, the iodinated nano- starch filler (e.g., without limitation, iodinated nano-starch bone beads or bone void fillers) has biostatic persistence, biocidal persistence, and / or prolonged biocidal activities, and may also be referred to as iodinated plaster, iodinated fillers, iodinated calcium hemi-hydrate beads or bone void fillers and iodinated bone beads or bone void fillers.
[0151] In certain embodiments, the iodinated nano-starch bone beads or bone void fillers are prepared by iodinating the nano-starch bone beads or bone void fillers as described supra in Section-28-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00III. In certain embodiments, the iodination step comprises soaking the nano-starch bone beads or bone void fillers in a molecular iodine solution as disclosed herein. In certain embodiments, the starch concentrations of the dry iodinated nano-starch bone beads or bone void fillers are from about 0.5 wt% to about 5 wt%.
[0152] In certain embodiments, the iodinated nano-starch bone beads or bone void fillers are prepared by a method comprising mixing the iodinated nano-starch suspension with calcium hemihydrate, and forming beads or bone void fillers. In certain embodiments, the ratio of the iodinated nano-starch suspension to calcium hemi-hydrate is about 1.3: 1 to about 2:1 by weight. In certain embodiments, the iodinated nano-starch suspension has a starch concentration of about 1 wt% to about 4 wt%, or about 0.5 wt% to about 5 wt%. In certain embodiments, the iodine concentration in the iodinated nano-starch suspensions ranged from 500 ppm to 10,000 ppm. In certain embodiments, the starch concentrations of the dry iodinated nano-starch bone beads or bone void fillers are from about 0.5 wt% to about 5 wt%.
[0153] In certain embodiments, the iodinated nano-starch bone beads or bone void fillers are formed by setting within about 5 to about 6 minutes at bed side after the mixing step.
[0154] In certain embodiments, the iodinated nano-starch bone beads or bone void fillers have improved compression strength values of the iodinated calcium hemi-hydrate beads or bone void fillers than calcium hemi-hydrate beads or bone void fillers incorporated with starch powder directly at equivalent concentration levels.
[0155] In certain embodiments, the molecular iodine concentration of the iodinated filler is about 100 ppm to about 0.5% by weight.
[0156] In certain embodiments, the molecular iodine concentration of the iodinated filler does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at room temperature on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0157] In certain embodiments, the molecular iodine concentration of the iodinated filler does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at about 4 °C on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.-29-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0158] In certain embodiments, the iodinated filler has biostatic persistence, biocidal persistence, and / or prolonged biocidal activities.
[0159] In certain embodiments, after applied to a subject, the iodinated filler remains biostatic persistent, biocidal persistent, and / or has a prolonged biocidal activity for at least about 30 minutes, or at least about 1 hour, at least about 6 hours, at least about 12 hours, or at least about 1 day.C. Iodinated liquid / media filtration material
[0160] In certain embodiments, the iodinated nano-starch product is an iodinated liquid / media filtration material, which can be inserted into a water filter bed. Such an iodinated liquid / media filtration material can have the same or similar compositions as described supra with respect to the iodinated bone void fillers. In certain embodiments, the iodinated liquid / media filtration material comprises natural calcium plaster iodinated by iodinated nano- star ch / ester suspensions.
[0161] In certain embodiments, the molecular iodine concentration of the iodinated liquid / media filtration material does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at room temperature on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0162] In certain embodiments, the molecular iodine concentration of the iodinated liquid / media filtration material does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at about 4 °C on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0163] In certain embodiments, the iodinated liquid / media filtration material has biostatic persistence, biocidal persistence, and / or prolonged biocidal activities.
[0164] In certain embodiments, after added to a water filter bed, the iodinated liquid / media filtration material remains biostatic persistent, biocidal persistent, and / or has a prolonged biocidal activity for at least about 30 minutes, or at least about 1 hour, at least about 6 hours, at least about 12 hours, at least about 1 day, at least about 2 days, at least about 1 week, at least about 2 weeks, at least about 1 month, at least about two months, or at least three months.I). Iodinated film
[0165] In certain embodiments, the iodinated nano-starch product is an iodinated film.-30-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0166] In certain embodiments, the iodinated film is prepared by applying a layer of iodinated nano-starch suspension and / or iodinated nano-starch / ester suspension to a surface; and drying the layer of iodinated nano-starch suspension and / or iodinated nano-starch / ester suspension to form an iodinated film on the surface. The iodinated film can be removed from the surface and be a freestanding iodinated film. Alternatively, the iodinated film can remain on the surface. For example, without limitation, the surface can be a bandage.
[0167] In certain embodiments, the molecular iodine concentration of the iodinated film is about 100 ppm to about 1% by weight.
[0168] In certain embodiments, the molecular iodine concentration of the iodinated film does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at room temperature on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0169] In certain embodiments, the molecular iodine concentration of the iodinated film does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at about 4 °C on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0170] In certain embodiments, the iodinated film has biostatic persistence, biocidal persistence, and / or prolonged biocidal activities.
[0171] In certain embodiments, the iodinated film remains biostatic persistent, biocidal persistent, and / or has a prolonged biocidal activity for at least about 30 minutes, or at least about 1 hour, at least about 6 hours, at least about 12 hours, at least about 1 day, at least about 2 days, at least about 1 week, at least about 2 weeks, at least about 1 month, at least about two months, or at least three months.E. Iodinated coating
[0172] In certain embodiments, the iodinated nano-starch product is an iodinated coating.
[0173] In certain embodiments, the iodinated coating is prepared by applying a layer of iodinated nano-starch suspension and / or iodinated nano-starch / ester suspension to a surface of an article; and drying the layer of iodinated nano-starch suspension and / or iodinated nano-starch / ester-31-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 suspension to form an iodinated coating on the surface of the article. The iodinated coat may have biostatic persistence, biocidal persistence, and / or prolonged biocidal activity, which affords the surface coated, as well as the article coated, the same or similar biostatic persistence, biocidal persistence, and / or prolonged biocidal activity. Examples of the surface of the article include, without limitation, the surface of the article that is in contact of a subject, especially articles that remain contact with and / or in the subject for an extended period. Examples of such articles include, without limitation, catheters, ports, wound treatment and / or care products (e.g., without limitation, gauze, suture, bandage, hydrogels, bone fillers), and surgical products (e.g., without limitation, hemostats, injectables, and dermal regeneration products) or portions thereof that have contact with the subject.
[0174] In certain embodiments, the molecular iodine concentration of the iodinated coating is about 100 to about 1% by weight.
[0175] In certain embodiments, the molecular iodine concentration of the iodinated coating does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at room temperature on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0176] In certain embodiments, the molecular iodine concentration of the iodinated coating does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at about 4 C on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0177] In certain embodiments, the iodinated coating has biostatic persistence, biocidal persistence, and / or prolonged biocidal activities.
[0178] In certain embodiments, the iodinated coating remains biostatic persistent, biocidal persistent, and / or has a prolonged biocidal activity for at least about 30 minutes, or at least about 1 hour, at least about 6 hours, at least about 12 hours, at least about 1 day, at least about 2 days, at least about 1 week, at least about 2 weeks, at least about 1 month, at least about two months, or at least three months.F. Iodinated injectables
[0179] In certain embodiments, the iodinated nano-starch product is an iodinated injectable.-32-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0180] In certain embodiments, the iodinated injectable is prepared by replacing part or all of water, aqueous solution or suspension, and / or water miscible solution / suspension in an injectable with the nano-starch suspensions, nano- star ch / ester suspensions, iodinated nano-starch suspensions, and / or nano-starch / ester suspensions disclosed herein.
[0181] In certain embodiments, the aqueous solution or suspension to be replaced is at a neutral pH. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 7. In certain embodiments, the aqueous solution or suspension to be replaced has a pH of about 6 to about 7.
[0182] In certain embodiments, the iodinated injectable is prepared by a method comprising mixing a molecular iodine solution disclosed herein with the nano-starch suspensions, nano- starch / ester suspensions, iodinated nano-starch suspensions, and / or nano-starch / ester suspensions disclosed herein.
[0183] In certain embodiments, the pH of the iodinated injectable is about 4.0 to about 6.0.
[0184] In certain embodiments, the molecular iodine concentration of the iodinated injectable is about 100 to about 1% by weight.
[0185] In certain embodiments, the molecular iodine concentration of the iodinated injectable does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at room temperature on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0186] In certain embodiments, the molecular iodine concentration of the iodinated injectable does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at about 4 C on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0187] In certain embodiments, the iodinated injectable has biostatic persistence, biocidal persistence, and / or prolonged biocidal activities.
[0188] In certain embodiments, the iodinated liquid / media filtration material remains biostatic persistent, biocidal persistent, and / or has a prolonged biocidal activity for at least about 30 minutes, or at least about 1 hour, at least about 6 hours, at least about 12 hours, at least about 1 day, at least-33-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 about 2 days, at least about 1 week, at least about 2 weeks, at least about 1 month, at least about two months, or at least three months.6. Iodinated hemostatic products
[0189] In certain embodiments, the iodinated nano-starch product is iodinated hemostatic product which can be iodinated with the L-SAMI suspensions. In certain embodiments, the hemostatic product comprises aluminum chloride and ferric sulfate in glycol carriers, e.g., without limitation, ViscoStat™ Clear-25% Aluminum Chloride and ViscoStat™-20% Ferric Sulfate by Ultradent.
[0190] In certain embodiments, the molecular iodine concentration of the iodinated hemostatic product does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at room temperature on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0191] In certain embodiments, the molecular iodine concentration of the iodinated hemostatic product does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% at about 4 °C on shelf in at least about a month, at least about three months, at least about six months, at least about 1 year.
[0192] In certain embodiments, the iodinated hemostatic product has biostatic persistence, biocidal persistence, and / or prolonged biocidal activities.
[0193] In certain embodiments, the iodinated hemostatic product remains biostatic persistent, biocidal persistent, and / or has a prolonged biocidal activity for at least about 30 minutes, or at least about 1 hour, at least about 6 hours, at least about 12 hours, at least about 1 day, at least about 2 days, at least about 1 week, at least about 2 weeks, at least about 1 month, at least about two months, or at least three months.V. USES OF IODINATED NANO-STARCH SUSPENSIONS, IODINATED NANO-STARCH / ESTER SUSPENSIONS, AND / OR IODINATED NANO- STARCH PRODUCTS DISCLOSED HEREIN.
[0194] Another aspect of the present disclosure relates to uses of the nano-starch suspensions, nano-starch / ester suspensions, iodinated nano-starch suspensions, iodinated nano-starch / ester-34-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 suspensions, and / or iodinated nano-starch products prepared according to the methods disclosed herein.A. Killing or Inhibiting the Growth of Microorganism
[0195] Another aspect of the present disclosure provides a method of treating or preventing a condition associated with a microorganism in a subject comprising contacting the subject with one or more of the iodinated nano-starch suspensions, iodinated nano-starch / ester suspensions and / or iodinated nano-starch products as disclosed herein.
[0196] In certain embodiments, the one or more of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein remain in the subject for a time period that the one or more of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein have one or more biocidal effects selected from the group consisting of biostatic persistent, biocidal persistent, and prolonged biocidal activities. In certain embodiments, the one or more of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein remain in the subject for a time period that the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein have an iodine flux that is sufficient to afford biostatic persistent, biocidal persistent, and prolonged biocidal activity. In certain embodiments, the one or more of the molecular iodine-infused polymers or molecular iodine-infused articles remain in the subject for at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 2 months, or 3 months. In certain embodiments, when in contact with biofilm, the biocidal persistent and prolonged biocidal activity of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product may be at least about 1 days, at least about 2 days, or at least about 3 days.
[0197] In certain embodiments, the microorganism is killed at the contact site or in vicinity of the contact site. In certain embodiments, the growth rate of the microorganism is reduced at the contact site or in vicinity of the contact site.-35-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0198] In certain embodiments, the method further comprises delivering a therapeutically effective amount or prophylactically effective amount of molecular iodine via the iodinated nanostarch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein. In certain embodiments, the delivery happens multiple times at the same interval or at different intervals between each delivery. In certain embodiments, the delivery happens at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 2 months, or 3 months after the one or more of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein are placed in the subject.
[0199] In certain embodiments, the microorganism is present at the contact site or in vicinity of the contact site in or on the subject. In certain embodiments, a biofilm is present at the contact site or vicinity of the contact site. In certain embodiments, more than one species of microorganism are present at the contact site or vicinity of the contact site.
[0200] Examples of the conditions treatable or preventable include, without limitation, infections caused by microorganism, e.g., without limitation, urinary tract infection, breast implant infections, wound infections. In certain embodiments, the infection is a chronic infection. In certain embodiments, the infection is resistant infection. In certain embodiments, the infection is a chronic urinary tract infection.
[0201] In certain embodiments, the subject is a human.
[0202] In certain embodiments, the condition to be treated or prevented is a tissue condition associated with the microorganism. In certain embodiments, the tissue is a mucosal tissue or a cutaneous tissue.
[0203] In certain embodiments, the mucosal tissue surrounds or is in a biological cavity. Examples of biological cavities include eye cavity, ear cavity, oral cavity, nasal cavity, vaginal cavity, rectal cavity, and urethral cavity.
[0204] In certain embodiments, the microorganisms to be killed of growth of which to be inhibited include one or more species selected from the group consisting of Candida albicans, C.-36-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 freundii, Escherichia coli, E. faecalis, Enterococcus faecium, Klebsiella pnuemoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, or Staphylococcus epidermidis.
[0205] In certain embodiments, the microorganisms to be killed of growth of which to be inhibited include one or more species selected from the group consisting of S. aureus, P. aeruginosa, E. coli, E. faecalis, and C. freundii.
[0206] In certain embodiments, the microorganisms to be killed of growth of which to be inhibited include Staphylococcus aureus.
[0207] Examples of the microorganism to be killed or growth of which to be inhibited include virus, bacteria, fungus, and protozoa.
[0208] Examples of bacteria to be killed or growth of which to be inhibited include grampositive and gram-negative bacteria, e.g., without limitation, Bacillus oleronius, C. freundii, E. faecalis, Enterococcus faecium, Klebsiella pnuemoniae. Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Erysipelothrix rhusiopathiae, Mycobacterium tuberculosis, Mycobacterium bovis, Escherichia coli, Extended Spectrum Beta Lactamase resistant E. coli (ESBL), Shigella flexneri, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Vibrio cholera, MRSA, Salmonella enterica, Gonorrhea, Syphilis, Shewanella algae, Shewanella putrefaciens, Chlamydia, Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittacci, Aeromonas hydrophila, Vibrio species, Pasteurella multocida, Stapylococcus species, Corynebacterium species, Pripionibacterium species, and antibiotic resistant bacteria, e.g., without limitation, antibiotic resistant flesh eating bacteria.
[0209] Examples of conditions associated with bacteria to be treated or prevented include tuberculosis, periodontitis, acne (e.g., without limitation, Propionib acterium acnes), rosacea, impetigo, cellulitis, folliculitis, blepharitis (e.g., without limitation, anterior blepharitis, posterior blepharitis, rosacea blepharitis), bacterial conjunctivitis, blepharoconjunctivits, bacterial corneal ulceration, post-operative endophthalmitis, endophthalmitis after intravitreal or intracameral injection, and infections caused by the bacterium (e.g., without limitation, urinary tract infections).
[0210] Examples of fungus to be killed or growth of which to be inhibited include Apophysomyces variabilis, Aspergillus, Basidiobolus ranarum, Blastomyces dermatitidi, Coccidioides (e.g., without limitation, Coccidioides posadasii, Coccidioides immitis), Conidiobolus-37-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00(e.g., without limitation, Conidiobolus coronatus, Conidiobolus incongruous), Epidermophyton, Fonsecaea (e.g., without limitation, Fonsecaea pedrosoi, Fonsecaea compacta), Fusarium, Geotrichum candidum, Herpotrichiellaceae (e.g., without limitation, Exophiala jeanselmei), Histoplasma (e.g., without limitation, Histoplasma capsulatum, Histoplasma duboisii), Hortaea werneckii, lacazia (e.g., without limitation, Lacazia loboi), Hyalohyphomycosis, Lichtheimia corymbifera, Malassezia furfur, Microsporum (e.g., without limitation, Microsporum canis, Microsporum gypseum), Mucor indicus, onychomycosis (e.g., without limitation, Distal subungual onychomycosis, Proximal subungual onychomycosis), Phialophora verrucose, Piedraia hortae, Pityrosporum, Pseudallescheria boydii, Rhizopus oryzae, Sporothrix schenckii, Syncephalastrum racemosum, Talaromyces marneffei, Trichophyton (e.g., without limitation, Trichophyton mbmm, Trichophyton mentagrophytes), and yeast (e.g., without limitation, Candida such as Candida albicans, Candida glabrata, Candida tropicalis, Candida lusitaniae; Cryptococcus neoformans; Pneumocystis such as Pneumocystis jirovecii).
[0211] Examples of conditions associated with fungus to be treated or prevented are Alternariosis, black Piedra, blastomycosis, chromoblastomycosis, conidiobolomycosis, favus, fungal folliculitis, fungal corneal ulceration, Lobomycosis, onychomycosis, Otomycosis, Phaeohyphomycosis Pityrosporum folliculitis, ringworm, tinea (e.g., without limitation, tinea pedis, tinea cruris, tinea barbae, tinea manuum, tinea unguium, tinea unguium, tinea faciei, tinea versicolon, tinea nigra, tinea corporis gladiatorum, tinea imbricate, tinea incognito), yeast infection (e.g., without limitation, seborrheic dermatitis, vaginal yeast infections).
[0212] Examples of protozoa to be killed or growth of which to be inhibited include Acanthamoeba, Leishmania parasites, trypanosoma, Entamoeba histolytica, and Toxoplasma gondii.
[0213] Examples of conditions associated with protozoa to be treated or prevented include Acanthamoeba infections (e.g., without limitation, Acanthamoeba corneal ulceration), Acanthamoeba keratitis, Leishmaniasis, trypanosomiases, Amebiasis, and Toxoplasmosis.B. Uses on Wound-Healing or Scar-Prevention
[0214] Another aspect of the present disclosure relates to a method of fostering wound-healing or preventing a scar of a subject comprising contacting the wound with one or more of the iodinated-38-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein (e.g., without limitation, wound dressing, sutures, artificial skin).
[0215] In certain embodiments, the iodinated nano-starch suspension, iodinated nano- starch / ester suspension and / or iodinated nano-starch product as disclosed herein is applied to a wound or tissue in proximity of the wound. In certain embodiments, the tissue is a mucosal tissue or a cutaneous tissue.
[0216] In certain embodiments, the wound to be healed is healed with a scar less severe than a similar wound healed without the treatment. In certain embodiments, the scar is less severe as characterized by one or more improvements, e.g., without limitation, reduction of the scar height, reduction of the scar surface, reduction of the thickness of the scar, improvement of the pliability of the scar, improvement of the texture of the scar, reduction of pigmentation of the scar, and reduction of vascularity of the scar. See, e.g., Fearmonti et al., “A Review of Scar Scales and Scar Measuring Devices,” Eplasty, 2010: 10 e43, which is incorporated by reference(https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC2890387 / , attached as Appendix I). In certain embodiments, the one or more improvements of the scar are at least about 10%, about 10% to about 100%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%. In certain embodiments, the reduction of the scar height, the reduction of the scar surface, or the reduction of the thickness of the scar are / is at least about 10%, about 10% to about 100%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%.
[0217] In certain embodiments, the wound to be healed in presence of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein is healed without a visible scar.
[0218] In certain embodiments, the wound to be healed in presence of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein is healed in a shorter time period in the presence of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein compared to similar wound healed without the presence of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein.-39-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0219] In certain embodiments, the wound to be healed in presence of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein is inflicted by a cut, a friction, cold, heat, radiation (e.g., without limitation, sunburn), a chemical, electricity, a microorganism infection, pressure, or a condition of the subject (e.g., without limitation, diabetes). For example, in certain embodiments, the subject is diabetic (i.e., a subject having a condition, and the condition is diabetes). Examples of wounds in a diabetic subject include bullosis diabeticorum (diabetic blisters), eruptive xanthomatosis, and neuropathic ulcers (e.g., without limitation, diabetic foot ulcers). In certain embodiments, the wound is a decubitus ulcer (i.e., pressure ulcer, pressure sore, or bedsore). In certain embodiments, the wound is a bum wound.C. Uses for Pre-, Post- and Intra-Operative Infection Prevention
[0220] Provided are embodiments of a method of treating a surgical site to foster healing, or prevent infection in a subject in need comprising contacting the subject with one or more of the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano- starch product as disclosed herein (e.g., without limitation, wound dressing, sutures, and artificial skin). In certain embodiments, the method of treating a surgical site is performed as a pre-surgical treatment, a post-surgical treatment, or a treatment during a surgery.
[0221] A surgical site refers to an incision site on a subject, or any part of a subject’s anatomy in organs or spaces which were opened or manipulated during a surgery. In certain embodiments, the incision site includes a superficial incision site, e.g., without limitation, involving skin or subcutaneous tissue. In certain embodiments, the incision site includes a deep incision site, e.g., without limitation, in tissues deeper than the skin or subcutaneous tissue, such as fascial and muscle layers.
[0222] In certain embodiments, the iodinated nano-starch suspension, iodinated nano- starch / ester suspension, and / or iodinated nano-starch product as disclosed herein is applied to a surgical site or tissue in proximity of the surgical site.
[0223] In certain embodiments, the iodinated nano-starch suspension, iodinated nano- starch / ester suspension, and / or iodinated nano-starch product as disclosed herein is applied to a surgical site pre-surgical, post-surgical, or during surgery. Examples of surgery include pleurodesis procedure, cytoreductive surgery, thoracic surgery, esophageal resection, complete resection or-40-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 pleural reductive surgery for thymoma, primary functional endoscopic sinus surgery, spinal surgery, and colonic resection.
[0224] In certain embodiments, the iodinated nano-starch suspension, iodinated nano- starch / ester suspension, and / or iodinated nano-starch product as disclosed herein is administered as an eyelid antisepsis prior, during, or after an eye surgery (e.g., without limitation, cataract surgery) or other procedures on or proximate to an eye (e.g., without limitation, intravitreal injection, intracameral injection). In certain embodiments, the eyelid antisepsis is applied to eyelid by hand or by the molecular iodine-infused polymer or molecular iodine-infused article (e.g., without limitation, an eyelid wipe).
[0225] In certain embodiments, the iodinated nano-starch suspension, iodinated nano- starch / ester suspension and / or iodinated nano-starch product as disclosed herein is applied to a surgical site comprising a chest cavity (i.e., a space between a subject’s lung and chest wall). For example, the iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein may be administered before, during, or after a pleurodesis procedure in a subject in need.D. Uses for Sanitizing One or More Articles
[0226] Provided herein are embodiments of sanitizing one or more articles or materials (e.g., without limitation, metals, polymers, fabrics, plants, and food) comprising placing the one or more articles or materials adjacent to one or more iodinated nano-starch suspension, iodinated nano- starch / ester suspension and / or iodinated nano-starch product as disclosed herein. In certain embodiments, the one or more articles or materials are placed in a sealed compartment comprising the one or more iodinated nano-starch suspension, iodinated nano-starch / ester suspension and / or iodinated nano-starch product as disclosed herein. In certain embodiments, the sealed compartment is made of the one or more iodinated nano-starch products as disclosed herein. In certain embodiments, the sealed compartment comprises one or more iodinated nano-starch products placed therein.-41-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00EXAMPLESExample 1. Preparation of embodiments of nano-starch suspensions from starch powders derived from potato, corn, maize, tapioca, rice, wheat, pea, barley, or banana.
[0227] Various starch powders derived from various plant sources (e.g., without limitation, potato, corn, maize, tapioca, rice, wheat, pea, barley, and banana) were used to prepare nano-starch suspensions as described in this example.
[0228] The starch powder (1 g) was mixed with glycerin (12 g) to provide a starch-glycerin mixture. Optionally, the starch powder was pre-heated to about 80°C for about 10 minutes before mixing with glycerin to reduce water content in the mixture. Subsequently, the starch-glycerin mixture was heated to about 160°C on a hot plate or benchtop electrical heater, or by microwave heater or processor to create a transparent starch-glycerin gel with a viscosity approximately 5 to 6 times that of pure glycerin. While the gel was still hot, 100 grams of warm water (e.g., without limitation, with a temperature ranging from about 60 °C to about 100 °C) was slowly added while stirring. The obtained mixture was then cooled to about 50°C and homogenized using a probe ultrasonic processor, with a power capacity of 1,800 W and a frequency of 15-20 kHz, for a few minutes, to obtain a nano-starch suspension. The obtained nano-starch suspension was nearly transparent to slightly turbid, depending on the type of starch utilized. Embodiments of nano-starch suspensions with various final starch concentrations (e.g., without limitation, about 0.4 wt% to about 4 wt%, 0.4 wt%, 0.5 wt%, 0.7 wt%, 1 wt%, 1.5 wt%, 2 wt%, 3 wt%, and 4 wt% ) were prepared using various ratios of starch: glycerin (1:5-20).Example 2. Viscosity over microwave time of starch-glycerin mixture with or without Nal.
[0229] A corn starch-glycerin mixture was prepared as described in Example 1 using microwave heating. The mixture of corn starch (1 g) and glycerin (12 g) was added into a 500 mL glass beaker and placed in a 2.2 cubic feet microwave oven for microwave at 1,250 W for 30 seconds. Figure 1 shows the gelling of the corn starch-glycerin mixtures and their viscosities as a function of time under microwave, as well as the temperature of the oven wall which may be lower than the mixture temperature. At the end of the 30 second heating cycle, the corn starch-glycerin mixture reached a temperature of about 160 °C when the oven wall temperature reached about 180 °C and a viscosity of about 5k mPa, and a starch-glycerin gel was formed. At this stage, 86 g of warm water-42-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00(e.g., without limitation, with a temperature ranging from about 60 °C to about 100 °C) was added with stirring, and the obtained mixture was processed with an ultrasonic homogenizer as described in Example 1 to provide nano-starch suspensions.
[0230] Note the temperature was temperature of the oven wall, which can be higher than that of the mixtures. For example, some mixtures had a temperature of 160 °C when the oven wall temperature was 180 °C. Similar patterns were observed when the starch tested was potato, rice or tapioca starch (data not shown).
[0231] Embodiments of nano-starch suspensions were prepared using the same methods described in this example with other starch (e.g., without limitation, wheat, and pea). Embodiments of nano-starch suspensions with various final starch concentrations (e.g., without limitation, 0.4 to 1.5 wt%) were prepared using various ratios of starch:glycerin (1 :5—1 :20).
[0232] Viscosity measurements were made by a custom-built graduated cylinder falling ball test set up and a free image processing software as described in Sarah H Ali et al 2019 J. Phys.: Conf. Ser. 1294 022002.Example 3. Preparation of embodiments of nano-starch suspensions with salt
[0233] When sodium or potassium salts were added into the starch-glycerin mixtures described in Examples 1 and 2, the resultant nano-starch suspensions (as described in Examples 1 and 2) had smaller average particle sizes and higher colloidal stabilities. The viscosities of the starch-glycerin mixtures in the presence of sodium or potassium salts did not increase after 20 seconds of microwave heating and transformed into a mixture of lower viscosity at 180°C. The sodium and potassium salts tested were Nal, KI, NaCl, KC1, and Rochelle salt. Table 1 lists average particle sizes of the nano- starch suspensions obtained from the starch-glycerin mixtures with or without salts according to the methods described herein.-43-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Table 1. Particle sizes (nm) based on turbidity measurements of nano-starch suspensions containing 1 wt.% starch, 1 wt.% salt, 12 wt.% glycerin and 86 wt.% water or 1 wt.% starch, 12 wt.% glycerin and 87 wt.% water.
[0234] The starch-glycerin mixtures with salt additives also demonstrated improvements in the ultrasonic homogenizer processing times compared to the starch-glycerin mixtures without salt. Their dispersion times in water were reduced as shown in Table 2, particularly for waxy maize starch (e.g., without limitation, com starch).Table 2. Ultrasonic homogenizer processing times (minutes) for nano-starch suspensions obtained from starch-glycerin mixtures with (1 wt.% starch, lwt.% salt, 12 wt.% glycerin and 86 wt.% water) or without (1 wt.% starch, 12 wt.% glycerin and 87 wt.% water) salt additives.
[0235] Embodiments of nano-starch suspensions were prepared using the same methods described in this example with other starch (e.g., without limitation, wheat, and pea). Embodiments of nano-starch suspensions with various final starch concentrations (e.g., without limitation, 0.4 to 1.5 wt%) were prepared using various ratios of starch:glycerin:salt (1 :(5~20):(0.3~l .5)).-44-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Example 4. Preparation of embodiments of nano-starch suspensions with another glycol
[0236] Nano-starch suspensions were also prepared from starch-glycerin mixtures described in Examples 1-2, which further included a glycol (e.g., without limitation, low molecular weight polyethylene glycol (PEG 200, and PEG 400) or propylene glycol). The glycol was added at a starch to glycol ratio of about 1 to 1;2.5 to provide a starch-glycerin-glycol mixture in the absence of salt and before the heat treatment at about 160 C, but after the pre-heating of the starch to reduce water content. Starch-glycerin mixtures with a glycol were easier and faster to be dispersed in water than the starch-glycerin mixtures without glycol or salt, as shown by the reduced ultrasonic processing times as shown in Table 3.Table 3. Ultrasonic homogenizer processing times (minutes) for nano-starch suspensions prepared from starch-glycerin mixtures with (1 wt.% starch, lwt.% glycol, 12 wt.% glycerin and 86 wt.% water) or without (1 wt.% starch, 12 wt.% glycerin and 87 wt.% water) glycol.
[0237] Embodiments of nano-starch suspensions were prepared using the same methods described in this example with other starch (e.g., without limitation, wheat, and pea). Embodiments of nano-starch suspensions with various final starch concentrations (e.g., without limitation, about 0.4 wt% to about 1.5 wt%) were prepared using various ratios of starch:glycerin:glycol (l:(5~20):(0.3~1.5)).Example 5. Preparation of embodiments of nano-starch suspensions with salt and glycol
[0238] Nano-starch suspensions may be prepared from starch-glycerin-glycol mixtures as described in Example 4, but the starch-glycerin-glycol mixtures further include one or more potassium and sodium salts as described in Example 3 (e.g., without limitation, Nal, KI, NaCl, KC1, and Rochelle salt). For example, the obtained nano-starch suspensions may have 1 wt.% starch, lwt.% glycol, 1 wt% of all salt(s), 12 wt.% glycerin and 85 wt.% water.-45-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Example 6. Preparation of embodiments of nano-starch / ester suspensions using lactic acid (LA) and glycerin
[0239] Embodiments of nano-starch / ester suspensions were prepared using waxy starches such as waxy corn or maize starch. The same method also was also applied to other unmodified starches such as starch from potato, tapioca, rice, wheat, and pea. One gram of waxy corn starch was mixed with equal weight of lactic acid (LA) (starch: LA, 1 : 1) to provide a starch-LA mixture atRT. Glycerin (10 g) was added to the starch-LA mixture to provide a starch-LA-glycerin mixture. The starch-LA- glycerin mixture was heated to about 160 °C and treated at this temperature for a duration of one minute (preferred microwave). Partial esterification of starch was achieved without catalysis (see: Int J Biol Macromol. 2020 Aug 1 : 156: 1316-1322. Doi: 10.1016Zj.ijbiomac.2019.il.171.). Note that lactic acid starch esterification in glycerin was not disclosed in prior art. Warm water (88 g, with a temperature ranging from about 60 °C to about 100 °C) was introduced slowly such that 1 percent starch in water suspension was obtained. Embodiments of nano-starch / ester suspension with starch concentration of 1 to 1.5% were prepared. Average starch particle sizes of the nano-starch / ester suspensions were approximately 70 nm, which were smaller than those of nano-starch suspensions with the same starch concentration but without salt or glycol. Embodiments of nano-starch / ester suspensions were also prepared using starch-LA-glycerin mixtures which further comprised salts as described in Example 3, with a starch to salt ratio of 1.
[0240] Embodiments of nano-starch / ester suspensions were prepared using the same methods described in this example with other starch (e.g., without limitation, potato, tapioca, rice, wheat, and pea). Embodiments of nano-starch / ester suspensions with various final starch concentrations (e.g., without limitation, about 0.4 wt% to about 4 wt%, about 0.4 wt% to about 1.5 wt%, 0.4 wt%, 0.5 wt%, 0.7 wt%, 1 wt%, 1.5 wt%, 2 wt%, 3 wt%, and 4 wt% ) were prepared using various ratios of starch:glycerin:LA:salt (1 :(8~10): 1 : 1 to 1 :(8~10): 10: 10) or starch:glycerin:LA (l :(8~10): l to l:(8~10):10).Example 7. Preparation of embodiments of nano-starch / ester suspensions using lactic acid (LA) and PEG.
[0241] Embodiments of nano-starch / ester suspensions were prepared using waxy starches such as waxy corn or maize starch, the same method was applied to other unmodified starches such as starch from potato, tapioca, rice, wheat, and pea. Instead of glycerin, a low viscosity low molecular-46-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 weight polyethylene glycol (PEG) was utilized. PEG tested was PEG200, PEG 400 and PEG 1500. One gram of waxy corn starch was mixed with equal weight of PEG, lactic acid, and a salt as described in Example 3 (starch: LA:PEG:salt = 1 : 1: 1: 1) to provide a starch-LA-PEG mixture. The starch-LA- PEG mixture was mixed at RT, then was heated up to 160 °C and treated at this temperature for a duration of one minute (preferred microwave). Note that lactic acid-starch esterification in PEG was not disclosed in prior art. Then, hot water (97 g, with a temperature ranging from 60 °C to 100 °C) was introduced slowly to provide a nano-starch / ester suspension with 1 wt% starch. Embodiments of the nano-starch / ester suspensions with a starch concentration of 1-1.5 wt% were prepared, and had average particle sizes of approximately 70 nm.
[0242] Embodiments of nano-starch / ester suspensions were prepared using the same methods described in this example with other starch (e.g., without limitation, potato, tapioca, rice, wheat, and pea). Embodiments of nano-starch / ester suspensions with various final starch concentrations (e.g., without limitation, about 0.4 to about 4 wt%, about 0.4 wt% to aboutl.5 wt%, 0.4 wt%, 0.5 wt%, 0.7 wt%, 1 wt%, 1.5 wt%, 2 wt%, 3 wt%, and 4 wt%) were prepared using various ratios of starch:PEG:LA:salt (1 :1 :1 :1 and 1 : 1 :2: 1).Example 8. Preparation of embodiments of nano-starch / ester suspensions using lactic acid (LA) and glacial acetic acid.
[0243] Embodiments of nano-starch / ester suspensions were prepared utilizing glacial acetic acid and lactic acid instead of lactic acid only as described in Example 5. A starch powder (1 to 1.5 g) was mixed with glacial acetic acid and lactic acid at RT (starch:glacial acetic acid: LA = 1 : 1 : 1) to provide a starch-acid mixture. The starch-acid mixture was heated to approximately 160 °C and maintained this temperature for no longer than 1 minute. While the mixture was hot, glycerin (starch:glycerin = 10) was added, and the mixture obtained was reheated to 160 °C for an additional minute. While the obtained mixture was hot, gradually added water to achieve a starch concentration of around 1 wt%, and homogenized the obtained mixture using an ultrasonic processor or homogenizer as described in Example 1, for a maximum of 5 minutes.
[0244] Embodiments of nano-starch / ester suspensions were prepared using the same methods described in this example with other starch (e.g., without limitation, potato, tapioca, rice, wheat, and pea). Embodiments of nano-starch / ester suspensions with various final starch concentrations (e.g., without limitation, about 0.5 wt% to about 1.5 wt%) were prepared using various ratios of-47-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 starch:glycerin:LA:AcOH:salt (1:8-10: 1 : 1 : 1 to 1:8-10: 10:10: 10) or starch:glycerin:LA:AcOH (1 :8-10:1 :1 to 1:8-10: 10: 10).Example 9. Preparation of embodiments of nano-starch / ester suspensions using glacial acetic acid.
[0245] Embodiments of nano-starch / ester suspensions were prepared using a method similar to that described in Example 7 without the presence of lactic acid. In this method, com starch (e.g., without limitation, 1.3 g) and glacial acetic acid (1 g) were mixed at RT. Subsequently, glycerin (e.g., without limitation, 11 g) was added in in the starch-glacial acetic acid mixture to provide a starchglycerin- AcOH mixture. The starch-glycerin-AcOH mixture was subjected to mechanical mixing while heated to 160 °C for a duration not exceeding one minute to provide a partial acetylated starch mixture. The viscosity changed during the heating process (Table 4). Then the mixture was dispersed and homogenized in water to achieve a nano-starch / ester suspension with a final starch concentration of approximately 1 wt% as described in Example 1. The average particle size of the nano-starch / ester suspension was around 85 nm. Embodiments of nano-starch / ester suspension was prepared according to the method described supra in this example, with the addition of a salt described in Example 3 (e.g., without limitation, Nal, 1 g), the viscosity change of the starch-glycerin-AcOH-Nal mixture during the heating process (Table 5) showed higher viscosities than the starch-glycerin-AcOH mixture with the same starch:glycerin:AcOH ratio(Table 4). The nano-starch / ester suspension prepared from the starch-glycerin-AcOH-Nal mixture had an average particle size of approximately 70 nm.Table 4. Viscosity changes during the heating of 1.3 g corn starch, 1.0 g glacial acetic acid and 11.0 g of glycerin mixture in a 1250 W microwave oven for half a minute.-48-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Table 5. Viscosity changes during the heating of 1.3 g corn starch, 1.0 g glacial acetic acid, 1.0 g of sodium iodide and 11.0 g of glycerin mixture in a 1250 W microwave oven for half a minute.
[0246] Embodiments of nano-starch / ester suspensions were prepared using the same methods described in this example with other starch (e.g., without limitation, potato, tapioca, rice, wheat, and pea). Embodiments of nano-starch / ester suspensions with various final starch concentrations (e.g., without limitation, about 0.4 wt% to about 4 wt%, about 0.4 wt% to about 1.5 wt%, 0.4 wt%, 0.5 wt%, 0.7 wt%, 1 wt%, 1.5 wt%, 2 wt%, 3 wt% and 4 wt%) were prepared using various ratios of starch:glycerin:AcOH:salt (1 :8-10: 1: 1 to 1 :8-10:10: 10) or starch: glycerin :AcOH (1 :8-10:1 to 1:8-10: 10).Example 10. Stabilities of the embodiments of the nano-starch suspension and nano-starch / ester suspension described in Examples 1-9.
[0247] The embodiments of the nano-starch suspension and nano-starch / ester suspension described in Examples 1-9 were placed in sealed glass jars stored at RT in dark.
[0248] The embodiments showed no sedimentation for over three months at RT when their starch concentrations were about 1.5 wt% or lower.-49-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00
[0249] The embodiments having higher starch concentrations (e.g., without limitation, up to about 4 wt%) started showing sedimentation before three months at RT. For example, some embodiments started showing sedimentation after about 1 day at RT when their starch concentrations were about 4 wt%.Iodination of molecular iodine with nano-starch suspensions and nano-starch / ester suspensions, and product applications thereof.
[0250] The embodiments of the nano-starch suspensions and nano-starch / ester suspensions prepared in Examples 1-9 were iodinated to provide embodiments of iodinated nano-starch suspensions and nano-starch / ester suspensions by mixing the nano-starch suspensions or nano- starch / ester suspensions with an iodination agent, e.g., without limitation, a solution of molecular iodine (e.g., without limitation, 0.1 wt% to 15 wt% molecular iodine) in a water-miscible solvent (e.g., without limitation, ethanol, acetone, DMSO, glycerin, propylene glycol, or a mixture thereof, e.g., without limitation, as referenced in W02023 / 019033)), a Lugol’s iodine solution in water, a PVPI solution (e.g., without limitation, buffered to be pH 4.5) containing 1% titratable iodine, or solid iodine, as described below. Examples of lugol’s iodine solution can be found at https: / / www.flinnsci.com / sds_413-iodine-solution-lugol / sds_413 / or https: / / carlylenutritionals.com / products / lugols-iodine-2-potassium-iodide-and-iodine-2-fl-oz. In one example, a lugol solution (20k PPM I2)used to iodinate a nano-starch suspension was prepared by dissolving KI (3.5 g) and 12 (2 g) in water (94.5 g).Example 11. Iodination of nano-starch suspensions or nano-starch starch / ester suspensions using solid iodine.
[0251] The embodiments of the nano-starch suspension and nano-starch / ester suspension described supra in Examples 1-9 were used for iodination with solid iodine. The embodiments of the nano-starch suspension and nano-starch / ester suspension were mixed with solid iodine (about 0.005 g to about 2.5 g forlOO g suspension, e.g., without limitation, 1 g) and an iodide (e.g., without limitation, Nal, KI, final iodide concentration is at least about 3 wt% to about 4 wt%) through gentle mechanical mixing.
[0252] The embodiments of the nano-starch suspension and nano-starch / ester suspension had a starch concentration of about 0.5 wt% to about 4 wt%, and some embodiments had a starch-50-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 concentration of about 1 wt% to about 1.5 wt%. Some embodiments used for iodination were prepared using starches from potato, tapioca, and com and showed better stabilities than iodinated nano-starch suspensions or nano-starch starch / ester suspensions using other starches from ice, wheat or pea.
[0253] Some embodiments of the nano-starch suspension and nano-starch / ester suspension already included an iodide, and additional iodide was added if needed to reach the total iodide concentration of at least about 3 wt% to about 4 wt%. In some examples, the iodide was added before iodine was added. In some examples, the iodide was added after iodine was added.
[0254] The concentrations of free iodine in the resulting iodinated nano-starch suspensions and nano-starch / ester suspensions were assessed using two methods: the potassium iodide starch oxidizer test paper (semi-quantitative) and hexane extraction. For the hexane extraction method, each iodinated sample (2-3 g) or PVPI solutions (control) was mixed with hexane in a separate vial. The obtained mixtures were gently shaken every half an hour for 4 hours to extract free iodine to the hexane phase, which turned from light pink to purple as more free iodine diffused from the aqueous phase to the oil phase. If the iodine-hexane extract color of iodine-hexane solution was light or regular pinkish color, a Hanna Iodine Colorimeter - Checker® HC device was used to measure iodine between 0 to 12 ppm. If the iodine-hexane extract color was darker purple (exceeding 12.5 ppm, range of the meter) the iodine-hexane extract was diluted such that it could be measured with the device and factor the dilution back into the measurement.
[0255] Free iodine concentrations of various water dilution of an embodiment of iodinated nano-starch suspension (1 wt% iodine for iodination, the nano-starch suspension prepared according to Example 3 from potato starch with a starch concentration of 1 wt%, glycerin concentration 10 wt%, and Nal 2 wt%) were measured and compared with water dilution of a 1% PVPI solution at equivalent levels (Table 6). Note similar data were observed for iodinated nano-starch / ester suspensions (1 wt% iodine for iodination, the nano-starch / ester suspension prepared according to Example 6 from potato starch with a starch concentration of 1 wt%, lactic acid concentration of 1 wt%, glycerin concentration 10 wt%, and Nal 2 wt%)-51-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Table 6. Free iodine level comparisons between water-diluted nano-starch (1%) solution with 1% iodine and a commercial PVPI solution with 1% titratable iodine concertation.Example 12. Iodination of nano-starch suspensions or nano-starch starch / ester suspensions using PVPI solutions.
[0256] It is known that buffered PVPI solutions with a pH of approximately 4.5 (range pH 4 to 5.5), when diluted beyond a ratio of 1 / 300 — such as at iodine concentrations below 10 ppm — exhibit significant instability, often becoming colorless within an hour, suggesting little free iodine remained in the dilution. PVP-I solutions are known to have an important “concentration anomaly”. Over a certain range of PVP-I concentrations, the free iodine concentration increases in more diluted concentrations of povidone-iodine. This paradoxical effect follows a “bell curve” at low concentrations less than 0.05% lose their povidone-iodine complex characteristics and behave like aqueous iodine, the free iodine concentration rises until peaking at 0.1% PVP-I, then decreases with further increased PVP-I concentration. Correspondingly, in vitro bactericidal efficacy of povidone iodine has been shown to increase at more dilute concentrations peaking around 0.1% to 1%, with relatively faster killing rates. However, at such dilution rates the solutions do not remain stable. As shown below, dilution of PVP-I using the nano-starch suspensions or nano-starch / ester suspensions prepared in Examples 1-8 provided suspensions with more free iodine and higher stability than dilution using water.
[0257] Conversely, when nano-starch suspensions or nano-starch starch / ester suspensions were employed for dilution of PVPI solutions instead of water, the resulting iodinated nano-starch suspensions or nano-starch starch / ester suspensions demonstrated increased levels of free iodine at-52-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 the equivalent dilution level while maintaining stability for over two months at room temperature (Table 7 for using a nano-starch suspension with a starch concentration of 1 wt% prepared according to Example 3 (potato starch, 10 wt% glycerin, and 1.5 wt % Nal) as the diluent). The water dilutions showed a rapid loss of color (suggesting a loss of free iodine) while the dilutions diluted with the nano-starch suspension kept their color (suggesting a retained free iodine level) after stored in sealed glass jars in dark for more than 60 days at RT.Table 7. Iodine concentration measured by colorimetric detection and stability of 10% PVPI buffered solution (with 1% iodine, pH 4.5) dilution with water or with nano-starch suspension (1 wt% starch).Example 13. Iodine stability of embodiments of iodinated nano-starch suspensions and iodinated nano-starch / ester suspensions iodinated using PVPI solutions.(I) Iodine stability under accelerated aging conditions simulating a one-year shelf-life stability.
[0258] An embodiment of iodinated nano-starch suspension (1 wt% starch) was prepared by mixing a nano-starch suspension prepared according to Example 3 (2 wt% potato starch, 12 wt% glycerin and 2 wt% Nal, 50 g) with a PVPI solution (1 wt% titratable iodine, phosphate buffer and citric acid, pH 4.5, 50 g). The mixture was stirred gently until a dark blue coloration was achieved. For comparison, the 1% PVPI solution was diluted to an equivalent concentration using deionized-53-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 water. Both dilutions were tested for b concentration and stability under accelerated aging conditions at 65 °C for a duration of 20 days, simulating a one-year shelf-life stability. Intermediate iodine titration measurements were recorded (Table 8A). The dilution made by the nano-starch remained by two orders of magnitude stable compared to the dilution made by water alone. Similar data (not shown) were observed when the PVPI solution was buffered using other buffer(s) (e.g., without limitation, triethanolamine and citric acid). Buffers with sodium hydroxide did not work well and should be avoided.Table 8A. Accelerated aging at 65°C; stability comparison of a 4.5 pH buffered commercial PVPI solution 50% diluted with the nano-starch and water, respectively. Twenty days at these conditions correspond to one year shelflife at RT.(II) Iodine stability under basic conditions
[0259] An embodiment of iodinated nano-starch suspension (1 wt% starch) was prepared by mixing a nano-starch / ester suspension prepared according to Example 6 (1 wt% potato starch, 12 wt% glycerin and 1.7 wt% Nal) with a first PVPI solution (1 wt% titratable iodine, 10% PVP of 8k Da molecular weight, phosphate buffer and citric acid, pH 4.5) to reach molecular iodine-54-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 concentration of 600 ppm. The mixture was stirred gently until a dark blue coloration was achieved, which is referred as I2-SAMI composition 1 in this example.
[0260] Many antibiotics lose efficacy between pH 7.4 to 9. However, pH of bioburden in chronic wounds is around 9 or higher. Molecular iodine in PVPI solutions and PVPI solutions diluted with water or saline could be quickly consumed under basic conditions, as shown by the color change from a brown solution (with molecular iodine) to clear (without molecular iodine). Unexpectedly, molecular iodine in PVPI solutions diluted with an embodiment of the nano-starch suspension or nano-starch / ester suspension remained stable for much longer time.
[0261] For comparison, the PVPI solution diluted with deionized water (unbuffered PVPI), the McKesson irrigation solution diluted with deionized water (the dilution is referred to as the McKesson dilution), and BD Surgiphor™ antimicrobial irrigation system (Surgiphor, ready -to-use aqueous PVP-I lavage solution, 600 ppm I2) were tested. All test solutions had an available molecular iodine concentration of 600 ppm and were treated with triethanolamine (TEA, 10%, pH 11) of equal weight, and observed for color change. The time it took for the test solution to turn clear is summarized in Table 8B below.Table 8B. Consumption of molecular iodine in test solutions under basic conditions.
[0262] The amount of available molecular iodine in the test solutions under basic conditions was measured by titration with sodium thiosulfate Na2S20s (Figure 5).
[0263] Similar results were observed from tests comparing the stability of molecular iodine under basic conditions between PVPI solution diluted with embodiments of SAMI suspensions and with aqueous carriers, as summarized in Table 8C below (data not shown).Table 8C. Additional dilutions of PVPI solution with the same embodiment of SAMI suspensions (nano starch / ester suspension prepared according to Example 6, 1 wt% potato starch, 12 wt% glycerin-55-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 and 1.7 wt% Nal) and the McKesson dilutions or McKesson irrigation solution for molecular iodine stability under basic conditions.Example 14. Preparation of two embodiments of iodinated nano-starch suspension using iodine solution in glycerin (2 wt% iodine) as the iodination agent, and I2 stabilities of same.
[0264] The I2 stability of two embodiments of iodinated nano-starch suspensions (titratable iodine concentrations of 300 ppm and 500 ppm, respectively; 1 wt% starch) were evaluated under accelerated thermal aging at sixty-five degrees Celsius. The two embodiments of iodinated nano- starch suspension were prepared by mixing a nano-starch suspension prepared according to Example 3 (1 wt% potato starch, 10 wt% glycerin, and 1 wt% Nal), with a 2% iodine solution in glycerol. To mitigate evaporative losses of iodine, meticulous precautions were taken, including sealing the containers with Teflon liners and tapes, as well as minimizing the headspace in the sealed sample jars. The measurements obtained from both solutions, tested over a period of 20 days, are presented in the table below, which corresponds to an estimated one-year shelf stability at room temperature.-56-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Table 9. Accelerated aging stability at 65 °C; comparisons between two iodinated nano-starch suspensions subjected to accelerated thermal aging at sixty-five degrees Celsius. The solutions were formulated with titratable iodine concentrations of 300 ppm and 500 ppm, incorporating 1 wt.% starch relative to the total solution concentration.Example 15. Preparation of iodinated nano-starch suspension using an aqueous iodine solution and evaluation of I2 outgassing from porcine skin applied with the iodinated nano-starch suspensionI) METHOD DESCRIPTION
[0265] Porcine skin was acquired from a local supermarket. Using a surgical knife, a rectangular piece of porcine skin (approximately 120 cm2) was excised. To expose the stratum granulosum and stratum spinosum layers of the epidermis, a gentle scraping (abrasion) was applied to the sample skin epidermis layer for a duration of 30 seconds, as described by Reneudeu et al. in their publication "Anim. Res. 55 (2006) 209-217." The skin sample was then immersed in 35 °C water for a period of 25 minutes to ensure hydration. Excess water was removed from the hydrated skin by wiping it multiple times with Kim Wipe tissues. The skin sample was subsequently divided-57-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 into several smaller rectangular samples, each measuring approximately 1 cm2. The dimensions of each sample were measured individually using a digital caliper.
[0266] Using a plastic cell spreader, approximately 12 microliters of a test solution (e.g., without limitation, iodine solution in glycerin (b concentration of 10k PPM), iodine solution in propylene glycol (I2 concentration of 10k PPM), a fortified nano-starch suspension (I2 concentration of 10k PPM, iodinated nano-starch suspension as described in this example below), and commercial PVP solution (1% I2), were deposited and spread evenly over the surface of the epidermis. This process lasted for 25 seconds. Any excess solution on the surface was removed by wiping with alcohol -wet Kim Wipes after 10 min treatment with the test sample. The treated skin samples were then placed inside a glass j ar and maintained at a temperature of 35 °C using a water bath. This allowed for off-gassing to occur from the treated samples.
[0267] At various time intervals, the treated skin samples were removed from the water bath and promptly fixed inside a Teflon lined vial cap using double-sided tape. The sides of the sample were filled with a thin Teflon thread seal tape. Prior to each measurement, a 10 mL glass vial was filled with deionized water in which 0.13 g of DMPD iodine indicator (Cas No. 536-46-9) was dissolved. This solution served as a reference for the Hanna Iodine colorimeter (as per manufacturer). An identical glass vial containing the dissolved DMPD was prepared and fitted with the cap carrying the skin sample. The sealed vial was then inverted and placed in a water bath at a temperature of 35 °C to facilitate iodine diffusion for a duration of three minutes (see Figure 2(a) as an example). The color of the solution underwent a change during this process (see Figure 2(b) as an example). Each skin sample was allowed to outgas for a different duration over a period of about 4 hours.II) PREPARATION OF AN IODINATED NANO-STARCH SUSPENSION WITH 10,000PPM IODINE SOLUTION AND OUTGAS SING EVALUATION FOR SAME
[0268] An embodiment of the iodinated nano-starch suspension with an iodine concentration of 10k PPM was prepared, and referred to as a “fortified nano-starch suspension” in this example.
[0269] Equal amounts of an iodine solution in propylene glycol (free iodine concentration 10k PPM) and a commercial povidone iodine solution (10,000 ppm I2, citric acid and phosphate buffered) were mixed to provide an iodine solution with titratable iodine concentration of 10,000 ppm, which is also referred to as the 1% iodine solution in this example. 1.3 g of starch was mixed with 10 grams of glycerin and 1 gram of Nal and microwave for a total amount of 30 seconds to a temperature of-58-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 about 160 Celcius (see Example 3). Upon cooling to about 50 degrees Celsius, the mixture was added to 100 grams of the 1% iodine solution described above yielding a solution containing about 1.15 wt.% starch. The final mixture was processed by ultrasonic homogenizer as described in Example 3. The obtained fortified nano-starch suspension was allowed to rest for 48 hours at RT prior to the initiation of any experimental procedures. The methodologies described above and, in the reference, were followed for the porcine skin test and the results are illustrated in Table 10 and Figure 3. The data presented compared the 10,000 ppm commercial povidone iodine solution with iodine solution in propylene glycol, iodine solution in glycerin, as well as the fortified nano-starch suspension, all having an iodine concentration of 10,000 ppm.Table 10. Iodine outgassing (10,000 ppm, fortified nano-starch suspension) from porcine skin by colorimetric detection.
[0270] Additional embodiments of the fortified nano-starch suspensions may be prepared by replacing the iodine solution in propylene glycol with an iodine solution in glycerol solution, iodine solution alcohol (e.g., without limitation, ethanol, and isopropanol), or a Lugol’s solution with the same iodine concentration (10k PPM or 1 wt%).-59-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Example 16. Preparation of iodinated resorbable calcium hemi-hydrate beads or bone void fillers using embodiments of the nano-starch suspension and iodinated nano-starch suspension described herein.
[0271] Resorbable calcium hemi-hydrate beads or bone void fdlers can be mixed and shaped at the site of application to facilitate new bone regeneration by serving as a passive osteoconductive scaffold, allowing for the remodeling of native bone. These beads or bone void fillers can be inserted into open bone voids or gaps that do not compromise the structural integrity of the bone and can effectively address injuries resulting from surgical procedures, osseous conditions, or trauma. The beads or bone void fillers are usually produced through the reaction of calcium hemi-hydrate (plaster of Paris) powder with water, resulting in the formation of calcium dihydratev, which are referred herein as calcium hemi-hydrate beads or bone void fillers. Typically, two to three antibiotics can be incorporated during mixing to prevent biofilm formation during the surgical placement of the calcium sulfate beads or bone void fillers. The standard mixing ratio is one part water to 1.3 to 2 parts plaster of Paris, enabling rapid setting within five to six minutes at bed side.
[0272] In this example, a nano-starch suspension or an iodinated nano-starch suspension was used to replace water in forming novel nano-composite beads or bone void fillers with the same mixing ratios. Such nano-starch suspensions or iodinated nano-starch suspensions had a starch concentration of about 1 wt% to about 4 wt%. In some embodiments, the starch concentrations of the dry beads or bone void fillers were from about 0.5 wt% to about 5 wt%. The beads or bone void fillers obtained were iodinated if iodinated nano-starch suspensions were used. The iodine concentrations in the iodinated nano-starch suspensions ranged from 500 ppm to 10,000 ppm.
[0273] Alternatively, when non-iodinated nano-starch suspensions were used to prepare noniodinated beads or bone void fillers, the beads or bone void fillers were soaked in an iodine solution, e g., without limitation, iodine solution in glycerin, propylene glycol, or DMSO as described in W02023 / 019033. In some examples the iodine solutions had molecular iodine concentrations between about 3,000 ppm and about 30,000 ppm. In some examples, the soaking process happened for a duration of about 30 seconds to about 1 minute.
[0274] After the iodine solution soaking procedure, the beads or bone void fillers may be directly placed at the surgical site or rinsed with deionized water for a duration of 2 to 5 seconds to-60-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 eliminate any surplus 12 solution or solvent (e.g., without limitation, glycerin, propylene glycol, or DMSO).
[0275] The iodinated beads or bone void fillers obtained from the methods described in this example were highly effective antiseptic composite material. Figure 4 illustrates the placement of two iodinated beads or bone void fillers on a MacConkey agar E. coli diffusion plate, demonstrating efficacy after 96 hours. Prior to their placement in the agar diffusion plates, the beads or bone void fillers were submerged in a 2% iodine solution in propylene glycol for a duration of 30 seconds.
[0276] The production of calcium hemi-hydrate beads or bone void fillers utilizing a nanostarch suspension, rather than incorporating starch powder directly at equivalent concentration levels, resulted in unanticipated enhancements in the compression strength values of the beads or bone void fillers, as illustrated in Table 11 below.Table 11. Compressive strength of dry composite calcium hemi-hydrate beads or bone void fillers measured with a portable compression tester 24 hours after preparation. Inclusion of nano-starch improves the mechanical properties of the beads or bone void fillers compared to no-starch or native starch added beads or bone void fillers.
[0277] From the foregoing, it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made-61-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 without deviating from the scope of the invention. Accordingly, the invention is not limited except as by the appended claims.Example 17. Evaluation of molecular iodine transportation across hydrophilic-lipophilic interfaces in various iodophor formulations.
[0278] The release and transport of molecular iodine from various antiseptic iodophors across hydrophilic-lipophilic interfaces were compared among various iodophor formulations diluted with water and two embodiments of iodinated nano-starch suspensions diluted with nano-starch suspension as disclosed herein.
[0279] Water dilutions of seven commercial products were evaluated in this investigation. Six formulations were iodophor-based antiseptics, while one was a dilute Lugol's iodine solution (1% w / v), all maintaining equivalent titratable iodine concentrations of 1%. All solutions were obtained directly from their respective manufacturers and utilized without further modification. Serial dilutions were prepared using deionized water. The commercial products examined in this study, including their inactive ingredients and buffering systems where applicable, are detailed in Table 12. Reagent grade heptane and 0.1, 0.01 and 0.001 N sodium thiosulfate solutions were purchased from Thermo Fisher Scientific, USA and used as received. Soybean lecithin mainly comprising phosphatidylcholine and phosphatidylethanolamine was purchased from Spectrum, USA and used as received. Starch indicator solution 1%, w / v aqueous solution (for iodometric titrations), was purchased from Thermo Fisher Scientific, USA and used as received.
[0280] Among the iodophor formulations, skin preparation and surgical scrub solutions (samples 1 and 2) contained 10% aqueous povidone iodine with one percent titratable iodine. The Povadyne® antiseptic (sample 6) consisted of PVPI powder that was dissolved in deionized water to achieve a 10% solution and subsequently titrated with 0.1 N thiosulfate solution to confirm 1% titratable iodine content. This solution was prepared to eliminate potential interference from buffering agents or other inactive ingredients in commercial products that could affect drug release dynamics. Two commercial swabstick products saturated with 10% povidone-iodine solution were also evaluated as samples 4 and 5 in Table 12. These consisted of cotton swab applicators immersed in PVPI solutions and contained within sealed, medical-grade pouches. Sample 5 was a powder dextran- based iodine, comprising 0.9% iodine bound to a water-soluble polysaccharide complex, developed as wound dressing for exudate absorption. In contrast to polyvinylpyrrolidone polymer, this-62-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 compound exhibited limited water solubility. To maintain homogeneity in the prepared solutions containing sample 5, continuous stirring was required throughout the measurement process. The dextrin based cadexomer polymer (crosslinked dextrin) iodine complex is significantly different than the povidone iodine complex. The dextrin-iodine is an iodophor where iodine is physically encapsulated within a polysaccharide matrix. Its structure consists of a helical polysaccharide backbone that traps linear polyiodide chains within its hollow, hydrophobic core. Upon exposure to water or wound exudate, the polymer swells and releases physically trapped iodine. Finally, a dilute Lugol's solution containing 1% titratable iodine in water, stabilized with potassium iodide, served as the control solution. This formulation contained no iodophors.Table 12. Commercially available antiseptics and their properties including inactive ingredients.Product Manufacturer % % % pH Buffer Inactive State SamplePVPI Iodine titrated ingredients iodineSkin prep solution McKesson 10.0 1.0 0.96 4.54 Yes Citric acid, Liquid 1 disodium phosphate, glycerin, water, sodium citrate, Tween80Povidone iodine Dynarex 10.0 1.0 0.97 4.00 Yes Disodium Liquid 2 prep solution phosphate, glycerin, citric acid, sodium citrate, Tween 80, waterPovidone -iodine Dukal 10.0 1.0 1.2 3.64 Yes Alkyl Liquid 3 swabsticks glucoside, citric acid, glycerin, hydroxy ethyl cellulose, nonoxynol- 10, potassium iodide, water, sodium hydroxidePovidone -iodine PDI 10.0 1.0 1.1 2.80 ? Water, Liquid 4 swabsticks sodium hydroxide lodosorb cadexomer Smith & n / a 0.9 0.86 2.88 No None Powder 5 iodine NephewPovadyne" antiseptic Millipore Sigma 10.0 1.0 0.97 2.90 No None Powder 6-63-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Dilute Lugol's Thermo-Fisher n / a 1.0 0.97 3.5 No Potassium Liquid 7 solution iodide
[0281] One of the two embodiments of the iodinated nano-starch suspension comprised 1% titratable iodine in a nano-starch suspension with 5% PVP (referred to herein as SAMI-PVPI). The other embodiment of the iodinated nano-starch suspension was prepared by mixing a nano-starch suspension with a molecular iodine solution in glycerin to a final 1% titratable iodine (SAMI-h).
[0282] A hydrophilic-lipophilic interface was created by mixing 5 g of the test solutions (e.g., aqueous iodophor solution, the SAMI-PVPI, the SAMI-I2, and their dilutions) with 50 g of heptane, with the heptane (oil phase) deliberately used in excess to serve as a large reservoir for molecular iodine diffusion across the interface. The sink condition was also tested by replacing iodine dissolved heptane solutions with a fresh medium after equilibrium to ensure that no sink conditions play a role in molecular iodine transport. To investigate the impact of PVPI concentration on iodine release and transport, at least five dilution ratios (1 :2, 1: 10, 1 :20, 1 :50, and 1: 100) were prepared for Samples 1- 7 using deionized water (Table 13), and 7 dilution ratios were prepared for SAMI-PVPI and SAMI- 12 using the same nano-starch suspension (Table 14) The iodine released into the heptane was quantified by sampling 2-3 mL of the solution and measuring its absorbance at 520 nm using UV- Vis spectroscopy (Tables 13 and 14). Equilibrium levels were reached within five hours of interface establishment. Changes in the concentration of free E in the oil phase are plotted against dilution ratio for Samples 1-7 (Figure 6, note that concentration is expressed in parts per million (ppm) which is equivalent to milligrams per liter (mg / L)).Table 13. Equilibrium partitioning of molecular iodine into the oil phase in various water dilutions of Samples 1-7.-64-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Table 14. Free molecular iodine in the oil phase in various dilutions of SAMI-I2 and SAMI-PVPI
[0283] Figure 7 shows mean (N=6) amount of molecular iodine released in mg / L or ppm from each iodophor sample as a function of total titratable iodine in each dilution level of various commercial iodophor / iodine products: Sample 1 (solid circle), Sample 2 (solid square), Sample 3 (solid triangle), Sample 4 (solid inverted triangle), Sample 5 (solid diamond), Sample 6 (solid star), and Sample 7 (solid pentagon). For instance, in the absence of dilution, a 5 g iodophor sample (i.e., Sample 1) contains 0.05 g of available iodine (500 ppm, denoted by the red arrow), with 4% (0.002 g or 20 ppm) partitioning into heptane. At a dilution factor of 10, the available iodine decreases to 0.005 g, yet approximately 69% (0.00345 g or 34.5 ppm) transfers to the heptane phase. Thus, although dilution reduces the total available iodine in the iodophor, it significantly enhances the-65-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00 transfer of free iodine to the lipophilic phase across all tested samples. Notably, with the exception of Lugol’s solution, all povidone-iodine samples exhibit increased iodine release at dilution ratios of 2, 10, and 50. In contrast, modified dextrin-iodine complex appears to rapidly release molecular iodine at a dilution ratio of 2, which may not facilitate the controlled iodine release that could be achieved through successive dilutions, potentially requiring replacement for further controlled release.
[0284] The amount of molecular iodine released from the SAMI-h and SAMI-PVPI as a function of total titratable iodine in each dilution level are summarized in Table 15.Table 15: Molecular iodine released from the SAMI-I2 and SAMI-PVPI as a function of total titratable iodine in various dilution level
[0285] Similar experiments were performed when heptane (the lipophilic phase) was saturated with 50 wt.% soybean lecithin. Figure 8 shows amount of iodine released in mg / L or ppm from various commercial iodophor samples as a function total titratable iodine in Sample 1 (solid circle), Sample 2 (solid square), Sample 3 (Solid triangle), Sample 4 (solid diamond), Sample 5 (inverted triangle), and Sample 6 (Solid pentagon). Table 16 shows additional data for samples 1-6 diluted at additional dilution rates and dilutions of SAMI-PVPI and SAMI-b.-66-183539184.2PCT / US25 / 44754 03 September 2025 (03.09.2025)Attorney Ref. 140183.8012.WO00Table 16. Molecular iodine (PPM) released from various commercial iodophor samples and SAMI-PVPI and SAMI-I2 as a function of the total titratable iodine in each sample when heptane (the lipophilic phase) was saturated with 50 wt.% soybean lecithin-67-183539184.2
Claims
AMENDED CLAIMS received by the International Bureau on 19 March 2026 (19.03.2026)1. A method for preparation of a nano-starch suspension comprising: i) heating a first mixture comprising glycerin and starch to form a first composition having a first viscosity, the water content of the first mixture is no more than about 10 wt%; and ii) adding water to the first composition to create a nano-starch suspension.
2. A method for preparation of a nano-starch / ester suspension comprising: a) mixing a starch with an organic acid to provide a starch-acid mixture; b) heating a second mixture comprising the starch-acid mixture and a glycol to form a second composition having a second viscosity, the water content of the second mixture is no more than about 10 wt%; and c) adding water to the second composition to create a nano-starch / ester suspension.
3. A method for preparation of an iodinated nano-starch suspension or iodinated nano- starch / ester suspension comprising:A) preparing a nano-starch suspension according to claim 1 or a nano-starch / ester suspension; andB) adding an iodination agent into the nano-starch suspension or nano-starch / ester suspension to form an iodinated nano-starch suspension or iodinated nano-starch / ester suspension.
4. A method for preparation of an iodinated nano-starch suspension comprises:I) heating a first mixture comprising glycerin and starch to form a first composition having a first viscosity, the water content of the first mixture is no more than about 10 wt%; andII) adding an aqueous solution of molecular iodine to the first composition to create the iodinated nano-starch suspension.
5. A method for preparation of an iodinated nano-starch / ester suspension comprises:I) mixing a starch with an organic acid to provide a starch-acid mixture;II) heating a second mixture comprising the starch-acid mixture and a glycol to form a second composition having a second viscosity, the water content of the second mixture is no more than about 10 wt%; andIII) adding an aqueous solution of molecular iodine to the second composition to create the iodinated nano-starch / ester suspension.
6. The nano-starch suspension prepared according to the method of claim 1.
7. The nano-starch / ester suspension prepared according to the method of claim 2.
8. The iodinated nano-starch suspension prepared according to the method of claim 3.
9. The iodinated nano-starch / ester suspension prepared according to the method of claim 3.
10. The iodinated nano-starch suspension prepared according to the method of claim 4.
11. The iodinated nano-starch / ester suspension prepared according to the method of claim 5.
12. A nano-starch product prepared using the nano-starch suspension of claim 6 and / or the nano-starch / ester suspension of claim 7 to replace part or all of one or more aqueous carriers used to prepare the product without the nano-starch suspension or nano-starch / ester suspension.
13. An iodinated nano-starch product prepared using the iodinated nano-starch suspension of claim 8 or claim 10 and / or the nano-starch / ester suspension of claim 9 or claim 11 to replace part or all of one or more aqueous carriers used to prepare the product without the iodinated nano-starch suspension or iodinated nano-starch / ester suspension.
14. The iodinated nano-starch product according to claim 13, wherein the iodinated nano-starch product is a dilution of a PVPI solution using the nano-starch suspension of claim 6, the nano- starch / ester suspension of claim 7, the iodinated nano-starch suspension of claim 8 or claim 10, and / or the nano-starch / ester suspension of claim 9 or claim 11.
15. The iodinated nano-starch suspension according to claim 8 or claim 10, the iodinated nano- starch / ester suspension according to claim 9 or claim 11, or the iodinated nano-starch product according to claim 14, having a shelf life of at least one year at room temperature.
16. The iodinated nano-starch suspension according to claim 8 or claim 10, the iodinated nano- starch / ester suspension according to claim 9 or claim 11, or the iodinated nano-starch product according to claim 14, having a shelf life of at least one year at 4 C.
17. The iodinated nano-starch suspension according to claim 8 or claim 10, the iodinated nano- starch / ester suspension according to claim 9 or claim 11, or the iodinated nano-starch product according to claim 14, wherein the molecular iodine concentration of the iodinated nano-starch suspension, the iodinated nano-starch / ester suspension, or the iodinated nano-starch / ester product does not reduce more than about 1%, no more than about 2%, no more than about 3%, no more than about 4%, or no more than about 5% under basic condition at room temperature for at least about 30 min, at least about 1 hour, at least about 1.5 hours, at least about 2 hours, at least about 2.5 hours, or at least about 3 hours.
18. A method of treating or preventing a condition associated with a microorganism in a subject comprising contacting the subject with one or more of the iodinated nano-starch suspension according to claim 8 or claim 10, the iodinated nano-starch / ester suspension according to claim 9 or claim 11, and the iodinated nano-starch product according to claim 14.
19. A method of fostering wound-healing or preventing a scar of a subject comprising contacting the wound with one or more of the iodinated nano-starch suspension according to claim 8 or claim 10, the iodinated nano-starch / ester suspension according to claim 9 or claim 11, and the iodinated nano-starch product according to claim 14.
20. A method of treating a surgical site to foster healing, or prevent infection in a subject in need comprising contacting the subject with one or more of the iodinated nano-starch suspension according to claim 8 or claim 10, the iodinated nano-starch / ester suspension according to claim 9 or claim 11, and the iodinated nano-starch product according to claim 14.
21. The method of claim 20, wherein the method is performed as a pre-surgical treatment, a post-surgical treatment, or a treatment during a surgery.