Method for delaying oxidation speed of easily oxidized product
By placing an oxygen absorber between the inner and outer packaging of the drug or pharmaceutically acceptable carrier or excipient, the problem of drug oxidative degradation is solved, thereby extending shelf life and ensuring safety.
Patent Information
- Application Number
- CN202511785909.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-01
- Publication Date
- 2026-02-27
AI Technical Summary
Existing pharmaceutical or pharmaceutically acceptable carriers or excipient packaging cannot effectively block oxygen from the air, leading to oxidative degradation, shortening shelf life, and potentially posing safety risks by adding antioxidants directly to pharmaceuticals.
It adopts a double-layer packaging structure with an oxygen scavenger between the inner and outer packaging materials. This agent includes iron powder, activated carbon, chlorogenic acid, and nanocomposite materials, forming a barrier layer to block oxygen and prevent oxidative degradation.
It effectively prevents the oxidative degradation of pharmaceuticals or pharmaceutically acceptable carriers or excipients, extends shelf life, and avoids the risk of contamination of pharmaceuticals by antioxidants, providing safe and reliable storage and transportation guarantees.
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of drug oxidation resistance, and particularly relates to a method for delaying the oxidation speed of an easily-oxidized product. BACKGROUND
[0002] A drug or a pharmaceutically acceptable carrier or excipient needs to be packaged to prevent oxidative degradation during storage and transportation, thereby prolonging the shelf life of the drug or the pharmaceutically acceptable carrier or excipient. The existing packaging form of the drug or the pharmaceutically acceptable carrier or excipient cannot effectively block oxygen in the air, resulting in easy oxidative degradation of the drug or the pharmaceutically acceptable carrier or excipient in the packaging content, which shortens the shelf life of the drug.
[0003] To solve the problem of avoiding the oxidation of the drug or the pharmaceutically acceptable carrier or excipient and prolonging the shelf life, while avoiding the safety risk caused by directly adding an antioxidant to the drug or the pharmaceutically acceptable carrier or excipient, some existing technologies have been disclosed. For example: Patent CN110448694A discloses a benzene sulfonic acid levamlodipine composition containing an antioxidant, a preparation method and application thereof. The patent realizes effective protection of benzene sulfonic acid levamlodipine by adding an antioxidant to the drug composition, reduces the generation of oxidative degradation impurities, and improves the stability of benzene sulfonic acid levamlodipine during the preparation process and storage of the preparation. However, the method adopted by the patent is to add an antioxidant to the drug, which may cause contamination of the drug.
[0004] Patent CN115258421A discloses a packaging method for improving the stability of a capsule and a capsule adopting the packaging method. The patent encapsulates the capsule in a drug packaging container, and a double-suction type deoxidizer is placed in the drug packaging container, which can prevent the oxidation of oxygen-sensitive drugs caused by contact with oxygen in the air, thereby increasing the related substances, while maintaining appropriate relative humidity to prevent the capsule shell from losing moisture and becoming brittle, thereby affecting the properties, dissolution, and the like of the drug, and effectively maintaining the quality of the drug. However, the patent is only suitable for the packaging of capsules, and has the problem of narrow application.
[0005] In the late 1970s, the deoxidizer Ageless developed by Mitsubishi Gas Chemical Company, Japan ® was introduced into commercial applications, and its forms included deoxidizing sachets, label stickers, or as a component part of food packaging materials.
[0006] The principle of oxygen removal is based on the chemical reaction between oxygen scavenger and oxygen. In the early development of oxygen scavenger, it can be divided into iron-based, sulfite-based, ascorbate-based, enzyme-based system, and oxidizable polyamide and olefinic unsaturated hydrocarbon types. This kind of oxygen scavenger can effectively reduce the oxygen content in the package to less than 0.01% of the oxygen content in the air, which is significantly better than the air packaging (MAP) - such as vacuum packaging or nitrogen charging technology, which can only reduce the oxygen content to 0.3%-3%.
[0007] However, such oxygen scavenger needs to be triggered by water, high temperature or light to start the oxidation reaction. For example, the principle of iron-based oxygen scavenger is that metallic iron is oxidized to ferrous hydroxide and ferric hydroxide; in addition to some accelerators, water is also needed to start the oxygen removal process, which forms a trigger mechanism that can be activated on demand. However, such oxygen scavenger is only suitable for products with high moisture content. SUMMARY
[0008] The purpose of the present application is to provide a method for delaying the oxidation rate of easily oxidizable products, by adding an oxygen scavenger between the inner and outer packaging materials of the pharmaceutical or pharmaceutically acceptable carrier or adjuvant, effectively isolating the external oxygen, effectively preventing the contamination of the pharmaceutical or pharmaceutically acceptable carrier or adjuvant by external oxygen, and ensuring the quality and safety of the product.
[0009] To this end, the present application provides the following technical solutions.
[0010] One aspect of the present application provides a method for delaying the oxidation rate of easily oxidizable products, sequentially arranging an inner packaging material and an outer packaging material outside the easily oxidizable product, and arranging an oxidizing agent between the inner and outer packaging materials.
[0011] In a preferred embodiment of the present application, the inner packaging material has gas barrier properties and is selected from one or more of polyethylene film bags, soda-lime glass bottles, and high-density polyethylene bottles.
[0012] In a preferred embodiment of the present application, the outer packaging material has light-proof and gas barrier properties and is selected from one or more of aluminum foil bags, paper boxes, and paperboard barrels.
[0013] In a preferred embodiment of the present application, the oxygen scavenger is selected from one or more of iron powder, activated carbon, chlorogenic acid, nanocomposite, and D-sodium isoascorbate.
[0014] In a preferred embodiment of the present application, the oxygen scavenger is placed in a container and arranged between the inner and outer packaging materials.
[0015] In a preferred embodiment of the present application, the container comprises polypropylene non-woven fabric, paper-plastic composite material, and ceramic / glass paper composite material.
[0016] In a preferred embodiment of the present invention, the amount of the oxygen scavenger added is 0.01 to 0.1% of the mass of the easily oxidized product.
[0017] In a preferred embodiment of the present invention, the duration of the oxygen scavenger is effective throughout the shelf life of the easily oxidized product.
[0018] In a preferred embodiment of the present invention, the easily oxidized product includes a pharmaceutical product, or a pharmaceutically acceptable carrier or excipient.
[0019] In a preferred embodiment of the present invention, the following steps are included: S1: Seal the easily oxidized product in the inner packaging material, and place the inner packaging material in the outer packaging material; S2: Place an oxygen absorber between the inner and outer packaging materials; S3: Sealing outer packaging material.
[0020] By employing the above technical solution, the present invention has at least the following advantages: This invention proposes a novel packaging method / form for easily oxidized products, such as pharmaceuticals or pharmaceutically acceptable carriers or excipients, to address the problems existing in the prior art. The product packaging method / form of this invention employs an inner and outer double-layer packaging structure, with an antioxidant layer disposed between the inner and outer packaging materials. The inner packaging material directly encapsulates the easily oxidized product, such as pharmaceuticals or pharmaceutically acceptable carriers or excipients; the outer packaging material protects the inner packaging material; the intermediate antioxidant layer effectively blocks oxygen from the air from entering the inner packaging material, thereby preventing oxidative degradation of the easily oxidized product and extending its shelf life. Simultaneously, by placing the antioxidant in a separate layer, the potential safety hazards associated with directly adding antioxidants to the product are avoided. This packaging method / form for easily oxidized products, such as pharmaceuticals or pharmaceutically acceptable carriers or excipients, not only effectively prevents oxidative degradation and extends shelf life but is also safe and reliable, preventing product contamination and providing strong protection for the storage and transportation of easily oxidized products, such as pharmaceuticals or pharmaceutically acceptable carriers or excipients.
[0021] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it in accordance with the contents of the specification, the preferred embodiments of the present invention are described in detail below. Detailed Implementation
[0022] In order to make the technical means, creative features, purposes and effects of the present application easy to understand, the technical solutions in the embodiments of the present application will be described clearly and completely below in combination with the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the scope of the present application.
[0023] As used herein, the term "drug product" refers to a substance used for the prevention, treatment, diagnosis of human diseases, the purposeful modulation of human physiological functions, and the prescription of indications or functional indications, usage and dosage. The drug product described in the present application refers to a product having a therapeutic and health care effect, and includes a product made of it as a main component and a product made of it as a constituent component or an additive. For example, the drug product can be an anticancer drug, a weight loss drug, a cardiovascular disease drug, an anti-type II diabetes drug, an antibacterial drug, an antiviral drug, a cosmetic, a skin care product, etc. In this context, the "drug product" can be any form of drug product, such as a solid, a liquid, etc.
[0024] As used herein, the term "pharmaceutically acceptable carriers and / or adjuvants" refers to carriers and / or adjuvants that are compatible with the subject and the active ingredient in pharmacology and / or physiology, which are well known in the art (see, for example, Remington's Pharmaceutical Sciences. Edited by Gennaro AR, 19th ed. Pennsylvania: Mack Publishing Company, 1995), and include but are not limited to: pH adjusters, surfactants, adjuvants, ionic strength enhancers, diluents, agents to maintain osmotic pressure, agents to delay absorption, preservatives.
[0025] In the present disclosure, the pharmaceutical excipients refer to excipients and additives used in the production of pharmaceutical products and the dispensing of prescriptions, which are substances other than active ingredients that have been reasonably evaluated in terms of safety and are included in pharmaceutical preparations. In addition to excipients, acting as carriers and improving stability, pharmaceutical excipients also have important functions such as solubilization, solubilization aid, controlled release, etc., which are important ingredients that may affect the quality, safety and effectiveness of pharmaceutical products. According to their sources, they can be divided into natural substances, semi-synthetic substances and synthetic substances. According to their functions and uses, they can be divided into solvents, propellants, solubilizers, solubilizers, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, humectants, osmotic pressure regulators, stabilizers, flow aids, flavorings, preservatives, suspending agents, coating materials, fragrances, anti-adhesion agents, antioxidants, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, release retardants, etc. According to their administration routes, they can be divided into oral, injection, mucosal, transdermal or local administration, nasal or oral inhalation administration and ocular administration, etc. The same pharmaceutical excipient can be used in pharmaceutical preparations for different administration routes, and has different functions and uses.
[0026] Oxidizable products refer to those that are easily chemically reacted with oxygen in the air, thereby causing changes in their properties. In the field of biological medicine, pharmaceutical products, pharmaceutically acceptable carriers and / or excipients are all susceptible to oxidation to some extent. Therefore, their storage methods are crucial.
[0027] Therefore, in one embodiment of the present application, a method for delaying the oxidation rate of an oxidizable product is provided, which realizes effective isolation from external oxygen by adding an oxygen scavenger between the inner packaging material and the outer packaging material of a pharmaceutical product or a pharmaceutically acceptable carrier or excipient, effectively avoids the contamination of the pharmaceutical product or the pharmaceutically acceptable carrier or excipient by external oxygen, and guarantees the product quality and safety.
[0028] Specifically, an inner packaging material, an outer packaging material and an oxidizing agent can be sequentially arranged outside the oxidizable product.
[0029] In the above embodiment, the inner packaging material is made of a material with gas barrier properties, and suitable materials include but are not limited to polyethylene film bags, soda-lime glass bottles, high-density polyethylene bottles, etc.
[0030] The outer packaging material is made of a material with light-blocking and gas-barrier properties, and suitable materials include but are not limited to aluminum foil bags, paper boxes, paperboard barrels, etc.
[0031] The key to the present application for delaying the oxidation rate of a product is the selection of an oxygen scavenger, and suitable oxygen scavengers include but are not limited to iron powder, activated carbon, chlorogenic acid, Nano-composites, sodium D-isoascorbate, etc. The use of the oxygen scavenger can ensure that the oxidation rate of the product is within the minimum range, thereby prolonging the shelf life of the product to be preserved.
[0032] The oxygen scavenger can be placed in a container and arranged between the inner wrapper and the outer wrapper. The container for placing the oxygen scavenger includes, but is not limited to, polypropylene non-woven fabric, paper-plastic composite material, ceramic / glass paper composite material, etc.
[0033] Further, the amount of the oxygen scavenger added is 0.01-0.1% of the mass of the oxidizable product, for example, can be 0.01%, 0.05% or 0.1% of the mass of the oxidizable product, preferably 0.05%. The duration of the oxygen scavenger is effective within the shelf life of the oxidizable product.
[0034] The oxidizable product described in the present application includes a pharmaceutical product, or a pharmaceutically acceptable carrier or excipient.
[0035] Specifically, the specific steps for achieving the delay of the oxidation rate of the oxidizable product include the following: S1: sealing the oxidizable product in the inner wrapper, and placing the inner wrapper in the outer wrapper; S2: placing the oxygen scavenger between the inner wrapper and the outer wrapper; S3: sealing the outer wrapper.
[0036] The delay of the oxidation rate of the product can be effectively achieved by the above method.
[0037] The following is described in detail with specific examples.
[0038] Unless otherwise specified, the polyethylene film bag, aluminum foil bag, sodium-calcium glass infusion bottle, and high-density polyethylene bottle involved in the embodiments of the present application are purchased from manufacturers that have been recorded on the CDE platform.
[0039] Example 1: First, seal the solid pharmaceutical excipient drug (poloxamer P188) in a polyethylene film bag, and place the polyethylene film bag with the sealed drug in an aluminum foil bag. Then, place 0.05% of the oxygen scavenger (consisting of 70% iron powder and 30% activated carbon according to the mass percentage, placed in polypropylene non-woven fabric) of the mass of the solid pharmaceutical excipient drug between the inner wrapper (polyethylene film bag) and the outer wrapper (aluminum foil bag). Finally, use a heat sealing machine to seal the aluminum foil bag, and obtain the packaged drug.
[0040] Example 2: First, seal the solid pharmaceutical excipient drug (poloxamer P407) in a polyethylene film bag, and place the polyethylene film bag with the sealed drug in a polyethylene film bag. Then, place 0.01% of the oxygen scavenger (consisting of 80% iron powder and 20% activated carbon according to the mass percentage, placed in polypropylene non-woven fabric) of the mass of the pharmaceutical excipient drug between the inner wrapper (polyethylene film bag) and the outer wrapper (polyethylene film bag). Finally, use a heat sealing machine to seal the polyethylene film bag, and obtain the packaged drug. Nano-composite 15%, chlorogenic acid 5%; placed in polypropylene nonwoven fabric). Finally, using a heat sealer, seal the polyethylene film bag to obtain the packaged drug product.
[0041] Example 3: First, seal the liquid pharmaceutical excipient drug product (polysorbate 80) in a soda-lime glass infusion bottle, and place the sealed drug product soda-lime glass infusion bottle in an aluminum foil bag. Then, place 0.1% of the oxygen scavenger (according to the mass percentage, the composition of the oxygen scavenger is: iron powder 80%, activated carbon 15%, chlorogenic acid 5%; placed in polypropylene nonwoven fabric) between the inner packaging soda-lime glass infusion bottle and the outer packaging aluminum foil bag. Finally, using a heat sealer, seal the aluminum foil bag to obtain the packaged drug product. Nano-composite 15%, chlorogenic acid 5%; placed in polypropylene nonwoven fabric). Finally, using a heat sealer, seal the polyethylene film bag to obtain the packaged drug product.
[0042] Example 4: First, seal the liquid pharmaceutical excipient drug product (polysorbate 20) in a high-density polyethylene bottle. And place the sealed drug product high-density polyethylene bottle in an aluminum foil bag. Then, place 0.01% of the oxygen scavenger (according to the mass percentage, the composition of the oxygen scavenger is: D-sodium isoascorbic acid 80%, activated carbon 15%, chlorogenic acid 5%; placed in polypropylene nonwoven fabric) between the inner packaging high-density polyethylene bottle and the outer packaging aluminum foil bag. Finally, using a heat sealer, seal the aluminum foil bag to obtain the packaged drug product.
[0043] Comparative Example 1: The only difference between this comparative example 1 and example 1 is that no oxidizing agent is used, and the rest is consistent with example 1: First, seal the solid pharmaceutical excipient drug product (poloxamer P188) in a polyethylene film bag, and place the sealed drug product polyethylene film bag in an aluminum foil bag. Then, using a heat sealer, seal the aluminum foil bag to obtain the packaged drug product.
[0044] Comparative Example 2: The only difference between this comparative example 2 and example 3 is that no oxidizing agent is used, and the rest is consistent with example 3: First, seal the liquid pharmaceutical excipient drug product (polysorbate 80) in a soda-lime glass infusion bottle, and place the sealed drug product soda-lime glass infusion bottle in an aluminum foil bag. Then, using a heat sealer, seal the aluminum foil bag to obtain the packaged drug product.
[0045] Test 1: Detection of the oxidation performance of the drug product In this test, the peroxide value of the drug product obtained in the above different examples and comparative examples is detected to evaluate the effect of different packaging methods on the oxidation rate of the drug product, wherein the peroxide value detection method includes the following steps: 1. Solvent preparation Sodium thiosulfate titration solution (0.01 mol / L): before titration, sodium thiosulfate titration solution (0.1 mol / L) is diluted 10 times to obtain the solution, which should be prepared freshly.
[0046] Potassium iodide test solution: take 16.5 g of potassium iodide, and add water to dissolve into 100 mL to obtain the solution, which should be prepared freshly.
[0047] 2. Detection method Take 5 g of the test sample, accurately weigh it, and place it in a 250 mL iodine bottle. Add 30 mL of a mixture of chloroform and glacial acetic acid (2:3), shake to dissolve, then add 0.5 mL of potassium iodide test solution, accurately shake and extract for 1 minute, then add 30 mL of water, and titrate with sodium thiosulfate titration solution (0.01 mol / L). During titration, slowly add the titration solution, and shake thoroughly until the yellow color almost disappears. Add 5 mL of starch indicator solution (0.5%), continue titration and shake thoroughly until the blue color disappears, and perform a blank test. The consumption of sodium thiosulfate titration solution (0.01 mol / L) in the blank test should not exceed 0.1 mL.
[0048] The volume (mL) of sodium thiosulfate titration solution (0.01 mol / L) consumed by the test sample is A, the volume (mL) of sodium thiosulfate titration solution (0.01 mol / L) consumed in the blank test is B, and the weight (g) of the test sample is W. The peroxide value POV is calculated according to the following formula: POV = 10 × (A-B) / W The results are shown in Table 1.
[0049] Table 1: Peroxide value statistics of different drugs ; As can be seen from the results in Table 1, compared with Comparative Examples 1 and 2, the oxidation of the drugs packaged in the packaging forms provided in Examples 1-4 of the present application is significantly improved, and the oxidation rate is significantly reduced.
[0050] The above description is only a preferred embodiment of the present application, and is not intended to limit the present application in any form. Although the present application has been disclosed with the preferred embodiment as above, it is not intended to limit the present application. Any person skilled in the art can make some changes or modifications to the above disclosed methods and technical contents without departing from the scope of the technical solution of the present application, and any simple modification, equivalent change and modification of the above embodiments based on the technical essence of the present application are still within the scope of the technical solution of the present application.
Claims
1. A method of retarding the rate of oxidation of an oxidizable product, characterized by, An inner packaging material, an outer packaging material and an oxidizing agent are sequentially arranged outside an oxidizable product.
2. The method of claim 1, wherein, The inner packaging material has gas barrier properties and is selected from one or more of polyethylene film bags, soda-lime glass bottles, and high-density polyethylene bottles.
3. The method of claim 1, wherein, The outer packaging material has light resistance and gas barrier properties and is selected from one or more of aluminum foil bags, paper boxes, and paperboard barrels.
4. The method of claim 1, wherein, the oxygen scavenger is selected from the group consisting of iron powder, activated carbon, chlorogenic acid, one or more of a nanocomposite, sodium D-isoascorbate.
5. The method of claim 1, wherein, The oxygen scavenger is placed in a container and arranged between the inner packaging material and the outer packaging material.
6. The method of claim 5, wherein, The container includes polypropylene non-woven fabric, paper-plastic composite material, and ceramic / glass paper composite material.
7. The method of claim 1, wherein, The oxygen scavenger is added in an amount of 0.01-0.1% of the mass of the oxidizable product.
8. The method of claim 1, wherein, The duration of the oxygen scavenger is effective within the shelf life of the oxidizable product.
9. The method of claim 1, wherein, The oxidizable product includes a pharmaceutical product or a pharmaceutically acceptable carrier or excipient.
10. The method according to any one of claims 1 to 9, characterized in that, The method includes the following steps: S1: sealing the oxidizable product in the inner packaging material and placing the inner packaging material in the outer packaging material; S2: placing the oxygen absorber between the inner packaging material and the outer packaging material; S3: sealing the outer packaging material.