Percutaneous absorption type foot bath composition capable of continuously releasing carbon dioxide and preparation method of percutaneous absorption type foot bath composition

Abstract

The invention belongs to the field of health-care physical therapy, and particularly relates to a transdermal absorption type foot bath composition capable of continuously releasing carbon dioxide and a preparation method of the transdermal absorption type foot bath composition. The transdermal absorption type foot bath composition capable of continuously releasing carbon dioxide is firstly provided, the transdermal absorption type foot bath composition comprises the following components: a CO2 generation system, a herbal active extract and a temperature-sensitive retardant, and through the synergistic interaction effect of CO2 and the herbal active extract, the transdermal absorption efficiency of active ingredients of traditional Chinese medicinal materials is promoted, so that the foot bath curative effect is improved; and better use experience is provided for the user. The invention further provides a preparation method of the transdermal absorption type foot bath composition capable of continuously releasing carbon dioxide, and the preparation method is used for producing the foot bath composition and providing a new generation of foot bath products different from traditional foot bath bags for the market.

Description

Technical Field

[0001] This invention belongs to the field of health care and physiotherapy, specifically relating to a transdermal absorption foot bath composition that continuously releases carbon dioxide and its preparation method. Background Technology

[0002] Foot baths, as a traditional Chinese medicine external therapy, have multiple benefits, including promoting blood circulation, clearing meridians, and eliminating toxins. In recent years, with the increasing awareness of health, foot bath packs containing Chinese herbal ingredients have become widely popular among consumers due to their convenience, representing a huge potential consumer market.

[0003] Patent searches revealed that some products attempt to incorporate "effervescent" technology to enhance the effects of foot baths. This technology utilizes the reaction between acidic substances in the herbal granules (or trace amounts of acid remaining during preparation) and added sodium bicarbonate to produce an effervescent effect, aiding in the dissolution of the drug through the disintegration of the gas.

[0004] However, the main purpose of existing carbonate-containing foot bath products is to use "effervescence" technology as a technical means to assist the drug's efficacy diffusion. The inventors found that the related technology has the following defects: (1) Weak gas generation mechanism: It only reacts with sodium bicarbonate using the weak acidic components in Chinese medicinal materials. Due to the large batch differences of Chinese medicinal materials and the fact that the acidity is usually weak, the amount of CO2 produced is small and unstable, and it cannot reach the concentration required to improve microcirculation. (2) Uncontrollable release rate: Ordinary effervescent tablets or disintegrating granules disintegrate rapidly after entering the water, resulting in uncontrollable and instantaneous CO2 release, which does not meet the requirements of sustained release. (3) Low CO2 utilization rate: The related technology only utilizes the physical stirring effect of CO2 and does not utilize the physiological effects (Bohr effect) and carrier effect of CO2 at high concentrations. (4) Difficulty in low temperature start-up: Some products need to be at high temperature (>45℃) to react violently, while the comfortable foot bath temperature range for the human body is 35-42℃. At this temperature, the reaction kinetics of ordinary preparations are often insufficient or too fast. Summary of the Invention

[0005] To address the problems of weak gas generation mechanisms, rapid release rates, low utilization rates, and difficulties in low-temperature start-up in related technologies, this invention first provides a transdermal absorption foot bath composition that continuously releases carbon dioxide and its preparation method, and briefly introduces its effects. The specific technical solution is as follows:

[0006] According to one aspect of the present invention, a transdermal foot bath composition for continuously releasing carbon dioxide is provided, comprising the following components: a CO2 generation system, herbal active extracts, and a temperature-sensitive inhibitor; the CO2 generation system is dispersed in a matrix formed by the temperature-sensitive inhibitor or is encapsulated by the temperature-sensitive inhibitor to form a microcapsule structure; the composition maintains the CO2 release time at a water temperature of 35-42°C for 20-30 minutes.

[0007] Furthermore, the CO2 generation system includes carbonates or bicarbonates and solid organic acids.

[0008] Furthermore, the solid organic acid includes, but is not limited to, at least one of citric acid, malic acid, tartaric acid, succinic acid, and fumaric acid; the carbonate or bicarbonate includes, but is not limited to, at least one of sodium bicarbonate, sodium carbonate, potassium bicarbonate, and potassium carbonate.

[0009] Furthermore, the molar ratio of the solid organic acid to the carbonate or bicarbonate is 1:(1.0-1.5).

[0010] Furthermore, the herbal active extract includes, but is not limited to, one or more extracts or powders of safflower, mugwort, motherwort, cinnamon twig, chicken blood vine, mulberry twig, luffa fruit, cowherb seed, salvia miltiorrhiza, cyperus rhizome, and tangerine peel; the content of the herbal active extract is 3-40% of the total mass of the foot bath composition.

[0011] Furthermore, the proportions of the herbal active extracts are as follows: 5-20 parts safflower, 10-30 parts mugwort, 10-25 parts motherwort, 5-15 parts cinnamon twig, 10-25 parts chicken blood vine, 5-15 parts mulberry twig, 5-15 parts luffa fruit, 5-15 parts vaccaria seed, 10-20 parts salvia miltiorrhiza, 5-15 parts cyperus rhizome, and 3-10 parts dried tangerine peel.

[0012] Furthermore, the temperature-sensitive inhibitor includes, but is not limited to, a mixture of one or more of polyethylene glycol (PEG), polyethylene glycol (PEG), poloxamer, stearic acid, and cetyl alcohol, and its phase transition temperature is adjusted to a suitable temperature range for foot baths through compounding.

[0013] Furthermore, the temperature-sensitive inhibitor is solid below 35°C to isolate acids and bases in the CO2 generation system; it undergoes a phase change at 3845°C to soften or melt and form a release channel.

[0014] Furthermore, the foot bath composition is a dry powder, granules, or effervescent tablet; the acid and alkali components in the CO2 generation system are respectively coated by the temperature-sensitive inhibitor to form independent microparticles with a core-shell structure, which are then mixed with the herbal active extract.

[0015] Furthermore, the foot bath composition releases carbon dioxide in water and maintains the carbon dioxide concentration in the water at more than 1000 ppm. The carbon dioxide bubbles act as carriers to adsorb the fat-soluble components of the herbal active extract to promote transdermal absorption.

[0016] According to another aspect of the present invention, a method for preparing a foot bath composition that continuously releases carbon dioxide at a mild water temperature is provided, comprising the following steps: S1. Heating and melting or dissolving the temperature-sensitive inhibitor, and spray-condensing and embedding or fluidizing solid organic acids and carbonates or bicarbonates respectively to obtain temperature-sensitive acid capsule particles and temperature-sensitive alkali capsule particles; S2. Mixing the acid and alkali capsule particles obtained in step S1 with the herbal active extract evenly; S3. Encapsulating or pressing the mixture under conditions below the phase transition temperature of the temperature-sensitive inhibitor.

[0017] Furthermore, the amount of the temperature-sensitive blocking agent used in step S1 is 5-30% of the amount of the coated material.

[0018] The present invention provides a transdermal absorption foot bath composition that continuously releases carbon dioxide and its preparation method, which solves the problems of weak gas generation mechanism, fast release rate, low utilization rate and difficulty in low temperature start-up in related technologies. It optimizes and improves the traditional Chinese medicine foot bath pack, and optimizes the health care effect of foot bath by utilizing the transdermal mechanism of CO2 and the temperature-sensitive control mechanism, providing users with a better user experience.

[0019] Compared with related technologies, the present invention has at least the following beneficial effects: 1. Temperature-sensitive long-term gas release: Adding solid organic acids provides sufficient reaction conditions, and introducing temperature-sensitive inhibitors (such as PEG) as a control method. By adjusting the molecular weight of the inhibitor, the CO2 release curve is changed from a high burst to a slow release; so that the foot bath pack can maintain a CO2 release cycle of 15-30 minutes at a water temperature of 35-42℃, covering the entire foot bath process.

[0020] II. CO2-Herbal Active Ingredient Carrier System: An independent organic acid-carbonate system is established to ensure sufficient CO2 generation; the Bohr effect is used to form a transdermal mechanism, allowing high concentrations of CO2 to pass through the skin into capillaries, causing vasodilation and significantly increasing local blood flow. At the same time, the lipid-soluble nature of CO2 carries herbal active ingredients through the skin barrier to enhance the therapeutic effect of foot bath.

[0021] 3. Mild conditions minimize drug efficacy loss: The usage temperature is set within the human body's comfortable temperature range (35-42℃). The gentle slow-release method avoids the violent boiling sensation when traditional effervescent tablets are added to water. The bubbles are fine and gentle, which improves user comfort while preventing the loss and denaturation of active ingredients in Chinese medicinal materials under high temperature and bubble impact. Attached Figure Description

[0022] The accompanying drawings, which form part of this application, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an undue limitation of the invention. In the drawings:

[0023] Figure 1 Flowchart of the preparation method for foot bath composition. Detailed Implementation

[0024] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0025] It should be noted that the terms "comprising" and "having" and any variations thereof in the specification, claims and accompanying drawings of this invention are intended to cover non-exclusive inclusion, such as a process, method, system, product or device that includes a series of steps or units, which is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such processes, methods, products or devices.

[0026] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0027] Example 1: Preparation of a temperature-sensitive foot bath pack 10. Preparation of coating solution: Mix PEG 1500 and PEG 1000 at a mass ratio of 2:3 until homogeneous, weigh out 300 g, heat and melt until a transparent and homogeneous liquid is formed, which is used as hot melt coating solution.

[0028] 11. Preparation of acid capsule microparticles: Weigh 1000 g of anhydrous citric acid (select anhydrous citric acid crystals with 30-60 mesh particles) and put it into the fluidized bed material chamber. Set the air inlet temperature to 30-32℃, the atomization pressure to 2.5 bar, and the spraying rate to 5-8 g / min. After 50% of the 300g wall material spraying amount has been sprayed, stop spraying, lower the air inlet temperature to 20℃, and continue blowing for 5 min before discharging and sieving to obtain the temperature-sensitive acid capsule.

[0029] 12. Preparation of alkaline capsule microparticles: Weigh 1200 g of sodium bicarbonate and put it into the fluidized bed material chamber. Set the inlet air temperature to 25-28℃, atomization pressure to 1.5-2.0 bar, and spraying rate to 10-18 g / min. Spray a small amount of coating liquid to make the fine powder aggregate into microparticles of 40-60 mesh. Then set the temperature to 30-32℃, atomization pressure to 2.5 bar, and spraying rate to 5-8 g / min. Coat the particles with the remaining hot melt coating liquid. After stopping the spraying, lower the inlet air temperature to 20℃ and continue blowing for 5 min. Then discharge and screen to obtain the temperature-sensitive alkaline capsule.

[0030] By coating the acid and base components of the CO2 generation system separately, dual isolation of acid and base is achieved to ensure stability during storage to the greatest extent and avoid premature CO2 explosion caused by moisture absorption.

[0031] 13. Preparation of herbal active extracts: (1) Extraction of volatile oil: 20 g of Artemisia argyi, 10 g of Cinnamomum cassia, 10 g of Cyperus rotundus, and 5 g of Citrus reticulata peel were weighed and crushed. They were then placed in a supercritical extraction vessel with a pressure of 25 MPa, an extraction temperature of 45℃, and a CO2 flow rate of 20 L / h for dynamic extraction for 2 h. β-Cyclodextrin was weighed at a mass ratio of volatile oil to β-cyclodextrin of 1:8. β-Cyclodextrin was added to 10 times its mass of distilled water and placed in a constant-temperature magnetically stirred water bath. The mixture was heated to 60℃ and stirred at 500 rpm until β-cyclodextrin was completely dissolved to obtain a saturated aqueous solution. The volatile oil was diluted with ethanol and added dropwise. After stirring for 2 h, the mixture was placed at 4℃ for 24 h to precipitate. The precipitate was then freeze-dried under vacuum to obtain white microcapsule powder.

[0032] (2) Water extraction: Weigh 15 g of safflower, 15 g of motherwort, 15 g of chicken blood vine, 10 g of mulberry twig, 10 g of luffa fruit, 10 g of vaccaria seed, and 15 g of salvia root, pulverize them, mix them with the residue after extracting the volatile oil, decoct with water, concentrate and dry into a dry extract powder. Mix the dry extract powder with the white microcapsule powder evenly to obtain the herbal active extract.

[0033] 14. Final Mixing and Packaging: Place the prepared temperature-sensitive acid capsules, temperature-sensitive alkali capsules, and herbal active extracts into a three-dimensional motion mixer, set the speed to 15 rpm, humidity to 30-40%, and mix for 10 minutes. Finally, use an automatic packaging machine to first package the mixed granules into non-woven bags (inner bags), and then seal the non-woven bags into aluminum-plated composite moisture-proof bags (outer bags), with each bag weighing 20 g net.

[0034] Example 2: Functional Testing of Foot Bath Packs 1. Measurement of CO2 concentration in water: (15) Pour 5 L of distilled water into the constant temperature water bath and set the temperature to 30℃ (low temperature group) and 40℃ (standard group). Use a dissolved carbon dioxide analyzer and a high-performance CO2 ion selective electrode to measure the CO2 concentration.

[0035] (16) The CO2 ion selective electrode was calibrated at two points using 100 ppm and 1000 ppm CO2 standard solutions. The slope was considered qualified when it fell within 50-60 mV / decade. The probe was then immersed 5 cm below the water surface, and the data recording mode was turned on (record once every 30 s). After the reading stabilized, the foot bath pack prepared in Example 1 was added. The peak concentration (ppm) and the time period when the concentration was maintained above 1000 ppm were continuously monitored for 30 min.

[0036] Table 1. CO2 Related Measurement Data The experimental results are shown in Table 1. At 30℃, almost no CO2 is released, while at 40℃, CO2 is released slowly, indicating that the solid state of PEG at low temperatures effectively isolates the reaction of the active ingredients. High-temperature melting opens the channels, allowing the active ingredients to react with each other, demonstrating the effectiveness of the temperature-sensitive gating design. The continuous CO2 release time can reach 26 minutes, indicating that the foot bath granules of this invention do not disintegrate instantaneously but release linearly and uniformly, with a peak value reaching 1350 ppm, proving the scientific formulation of the CO2 generation system.

[0037] 2. Determination of the transdermal penetration rate of safflower yellow pigment: (17) Abdominal skin from isolated SD rats was selected. After removing subcutaneous fat and fascia, the skin was soaked in physiological saline and fixed with the stratum corneum facing upwards. The treated bark was then fixed between the supply chamber (upper chamber) and the receiving chamber (lower chamber) of the Franz diffusion cell, with an effective permeation area of ​​2.8 cm². 2 Fill the lower chamber with approximately 15 mL of receiving solution (PBS, pH 7.4), turn on the magnetic stirrer (300 rpm), and set the water bath jacket temperature to maintain at 37°C.

[0038] (18) Experimental groups were formed. Experimental group: Take the mixed particles of Example 1 and dissolve them in 45℃ warm water to make the concentration 4g / L (consistent with the actual concentration of foot bath). When microbubbles are generated, immediately take 2 mL of the solution and add it to the supply chamber (upper chamber). Control group: Take 4 g / L of pure herbal extract solution without CO2 generation system substances and add it to the supply chamber.

[0039] (19) Sampling: At 5 min, 10 min, 15 min, 20 min and 30 min after administration, 1 mL of receiving solution was taken from the sampling port of the lower chamber and immediately supplemented with fresh PBS (pH 7.4) at the same temperature and volume.

[0040] (20) Sample preparation: Take 200 μL of each time period sample, dilute it 10 times with distilled water, vortex mix it, filter it through a 0.45 μm filter membrane, and put it into a liquid chromatography vial for HPLC determination of the content of hydroxysaffron yellow pigment A. The chromatographic conditions are set as follows: column C18 (250 mm × 4.6 mm, 5 μm); mobile phase is methanol-0.5% phosphoric acid solution (30:70); detection wavelength is 403 nm. Calculate the cumulative transmittance (%) = (cumulative transmittance / total amount of drug added to the supply chamber) × 100%.

[0041] Table 2. Data on the transdermal penetration rate of safflower yellow pigment The experimental data are shown in Table 2. At 5 minutes, the permeability of the control group was only 0.68% due to the skin barrier effect, while the permeability of the experimental group reached 3.6% at the same time. This indicates that the large number of CO2 bubbles generated by this invention effectively opened the skin barrier upon contact with the skin, significantly shortening the time required for the drug to enter the skin. The final permeability of the control group was 16.46%, while that of the experimental group was 60.34%, resulting in an approximately 3.7-fold increase in drug utilization. This effectively demonstrates the synergistic effect between the CO2-herbal active ingredient circulation system of this invention. Specifically, the CO2 bubbles, acting as a hydrophobic carrier, encapsulate and carry the drug components through the lipophilic skin barrier while continuously releasing a high concentration of CO2, maintaining a high transmembrane concentration gradient and providing continuous penetration power. This constructs an efficient transdermal drug delivery system and provides a convenient and highly effective foot bath composition and its preparation method.

[0042] The above description represents the preferred embodiments of the present invention. It should be noted that all reagents and materials used in the embodiments of the present invention, unless otherwise specified, are standardized products that can be obtained through conventional commercial channels. However, it should be understood that those skilled in the art may choose equivalent products from other suppliers, which does not depart from the scope of protection of the present invention. For those skilled in the art, several improvements and modifications can be made without departing from the principles described in the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A transdermal foot bath composition that continuously releases carbon dioxide and its preparation method, characterized in that, The composition comprises the following components: a CO2 generation system, herbal active extracts, and a temperature-sensitive inhibitor; the CO2 generation system is dispersed in a matrix formed by the temperature-sensitive inhibitor or is encapsulated by the temperature-sensitive inhibitor to form a microcapsule structure; the composition maintains the CO2 release time at a water temperature of 35-42°C for 20-30 minutes.

2. The foot bath composition according to claim 1, characterized in that, The CO2 generation system includes carbonates or bicarbonates and solid organic acids.

3. The foot bath composition according to claim 2, characterized in that, The solid organic acid includes, but is not limited to, at least one of citric acid, malic acid, tartaric acid, succinic acid, and fumaric acid; the carbonate or bicarbonate includes, but is not limited to, at least one of sodium bicarbonate, sodium carbonate, potassium bicarbonate, and potassium carbonate; the molar ratio of the solid organic acid to the carbonate or bicarbonate is 1:(1.0-1.5).

4. The foot bath composition according to claim 1, characterized in that, The herbal active extract includes, but is not limited to, one or more of the following: safflower, mugwort, motherwort, cinnamon twig, chicken blood vine, mulberry twig, luffa fruit, cowherb seed, salvia miltiorrhiza, cyperus rhizome, and dried tangerine peel; extracts or powders; the content of the herbal active extract is 3-40% of the total mass of the foot bath composition.

5. The foot bath composition according to claim 5, characterized in that, The herbal active extract is formulated in the following proportions: 5-20 parts safflower, 10-30 parts mugwort, 10-25 parts motherwort, 5-15 parts cinnamon twig, 10-25 parts chicken blood vine, 5-15 parts mulberry twig, 5-15 parts luffa fruit, 5-15 parts vaccaria seed, 10-20 parts salvia miltiorrhiza, 5-15 parts cyperus rhizome, and 3-10 parts dried tangerine peel.

6. The foot bath composition according to claim 1, characterized in that, The temperature-sensitive blocking agent includes, but is not limited to, a mixture of one or more of polyethylene glycol (PEG), poloxamer, stearic acid, and cetyl alcohol, and its phase transition temperature is adjusted to a suitable temperature range for foot baths through compounding; the temperature-sensitive blocking agent is solid below 35°C to isolate acids and bases in the CO2 generation system; it undergoes a phase transition at 3845°C to soften or melt and form a release channel.

7. The foot bath composition according to claim 1, characterized in that, The foot bath composition is a dry powder, granules, or effervescent tablet; the acid and alkali components in the CO2 generation system are respectively coated by the temperature-sensitive inhibitor to form independent microparticles with a core-shell structure, and then mixed with the herbal active extract.

8. The foot bath composition according to claim 7, characterized in that, The foot bath composition releases carbon dioxide in water and maintains the carbon dioxide concentration in the water at more than 1000 ppm. The carbon dioxide bubbles act as a carrier to adsorb the fat-soluble components of the herbal active extract to promote transdermal absorption.

9. A method for preparing a transdermal foot bath composition that continuously releases carbon dioxide as described in any one of claims 1-8, characterized in that, Includes the following steps: S1. The temperature-sensitive inhibitor is heated to melt or dissolve, and then spray-condensed or fluidized bed encapsulation is performed on the solid organic acid and carbonate or bicarbonate to obtain temperature-sensitive acid capsule microparticles and temperature-sensitive alkali capsule microparticles; S2. The acid and alkali capsule microparticles obtained in step S1 are mixed evenly with the herbal active extract; S3. The mixture is encapsulated or pressed into shape under conditions lower than the phase transition temperature of the temperature-sensitive inhibitor.

10. The preparation method according to claim 9, characterized in that, The amount of the temperature-sensitive blocking agent used in step S1 is 5-30% of the amount of the coated material.

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