Medical polypropylene and preparation method thereof

Abstract

The invention provides medical polypropylene and a preparation method thereof. The preparation method comprises the following steps: polymerizing propylene to obtain a polypropylene crude product; sequentially purifying, drying and granulating the polypropylene crude product to obtain the medical polypropylene, a purifying agent adopted for purification comprises a C5-C20 alkane solvent and a difunctional group additive; the weight ratio of the hydrocarbon solvent to the difunctional group additive is (1-13): (1-3). The medical polypropylene prepared by the preparation method is relatively low in precipitate content.

Description

Technical Field

[0001] This invention relates to a pharmaceutical-grade polypropylene and its preparation method, belonging to the field of pharmaceutical-grade polypropylene. Background Technology

[0002] Currently, the main polymer materials used in pharmaceutical packaging materials include polypropylene, polyethylene, polyvinyl chloride, polyethylene terephthalate, and hydrogenated styrene thermoplastic elastomer. Among them, polypropylene has become the main raw material for pharmaceutical packaging materials due to its high safety, light weight, good temperature resistance, and excellent mechanical and optical properties, accounting for more than 40%. It is mainly used in infusion bottles, upright infusion bags, multi-layer composite infusion soft bags, ampoules, solid medicine bottles, and medical blister packs.

[0003] Because some components of polypropylene pharmaceutical packaging materials can migrate into drugs during direct contact and potentially enter the human body via the route of administration, posing a threat to safe medication use, the National Pharmaceutical Packaging Material Standard imposes limits on the non-volatile matter in the leachate of polypropylene pharmaceutical packaging materials. Specifically, it requires that the non-volatile matter content after extraction with water, ethanol, and n-hexane must not exceed the specified limits. However, in actual pharmaceutical packaging material testing, the incidence of non-volatile matter content exceeding the standard for n-hexane is relatively high, representing a significant risk factor. The regularity of the polypropylene chain structure and its relative molecular mass have a significant impact on the n-hexane leachate content.

[0004] CN104231446B discloses a low-particulate-emission medical polypropylene material, its preparation method, and its application. The material is prepared from the following components in parts by weight: 50-80 parts polypropylene, 1-5 parts low molecular weight polyolefin wax, 10-35 parts vinyl elastomer, 5-15 parts auxiliary crosslinking elastomer, 0.005-0.05 parts modified peroxide, and 0.01-0.5 parts antioxidant. The polypropylene, vinyl elastomer, auxiliary crosslinking elastomer, and antioxidant are mixed evenly and added to an extruder. The mixture is melt-kneaded at 150-200°C. Then, the modified peroxide and low molecular weight polyolefin wax are mixed and dispersed evenly and added to the extruder for continuous extrusion. After water cooling and pelletizing, the medical polypropylene material is obtained. This material can be used to prepare combined three-caps for large-volume infusion packaging, medical and health equipment, or pharmaceutical storage containers.

[0005] CN107652541A discloses a polypropylene medical infusion set material, prepared from the following raw materials in parts by weight: 50-100 parts polypropylene resin, 5-9 parts nucleating agent, 2-4 parts antistatic agent, 2-8 parts toughening agent, 0.2-0.7 parts antioxidant, 0.5-1 part lubricant, and 0.2-0.5 parts antibacterial agent. The raw materials used in this invention have good toughness, high fluidity, and high transparency. Furthermore, the addition of nano-Ag-Ti antibacterial agents to the raw materials gives them antibacterial properties, making them safer to use.

[0006] CN101792555A discloses a polypropylene interface material for plastic infusion containers and its preparation method. The material mainly uses 81.6% medical-grade polypropylene, 3.2% medical-grade polyethylene, 15% medical-grade elastomer, 0.1% primary antioxidant, and 0.1% secondary antioxidant by weight as raw materials. Through processes of batching (weighing), mixing, extrusion, cooling, and pelletizing, a modified polypropylene material with high toughness, low melting point, meeting medical standards, and capable of welding with non-PVC films is prepared. It is particularly suitable as an interface material for various pharmaceutical packaging materials such as plastic infusion containers, significantly reducing production costs while exhibiting superior performance compared to similar foreign products.

[0007] CN103628167B discloses a novel method for preparing biocompatible medical-grade polypropylene monofilament. The method uses medical-grade polypropylene chips and pearl powder as raw materials. After kneading in a kneader, the mixture is melt-extruded into fine monofilaments using a conventional screw extruder. After water bath cooling, solidification, stretching, and heat setting, the filaments are wound into shape to obtain polypropylene monofilaments modified with pearl powder. The monofilaments have a diameter of 0.07-0.20 mm, a fineness of 35-300 dtex, a tensile strength of 3.0-5.0 cN / dtex, an elongation at break of 15-30%, and a pearl powder content of 1-5%. MTT assay results show a cytotoxicity rating of 0. The product exhibits good stability and uniformity, with mechanical properties reaching the level of ordinary medical-grade polypropylene monofilaments, and superior biocompatibility compared to ordinary medical-grade PP monofilaments.

[0008] However, the existing technology for preparing pharmaceutical-grade polypropylene through blending modification involves complex processes and results in high polypropylene precipitate content, which is detrimental to industrial application. Therefore, it is necessary to provide a new method for preparing pharmaceutical-grade polypropylene to address these issues. Summary of the Invention

[0009] To address the aforementioned technical problems, the present invention aims to provide a pharmaceutical-grade polypropylene and its preparation method, wherein the pharmaceutical-grade polypropylene has a low content of precipitates.

[0010] To achieve the above objectives, the present invention provides a method for preparing pharmaceutical-grade polypropylene, comprising: polymerizing propylene to obtain crude polypropylene product;

[0011] The crude polypropylene product is purified, dried, and granulated sequentially to obtain pharmaceutical-grade polypropylene.

[0012] The purification agents used include C5-C20 alkane solvents and bifunctional additives with the structure shown in Formula I;

[0013]

[0014] In Formula I, R1 is a C2-C5 alkyl group, R2 is a C1-C3 alkylene group, and R3 is a C1-C4 alkyl group. The weight ratio of the hydrocarbon solvent to the bifunctional additive is 1-13:1-3.

[0015] The present invention utilizes the above-mentioned bifunctional additives and C5-C20 alkane solvents to synergistically purify and polymerize the crude polypropylene product. This not only reduces the ash content of the product, but more importantly, the bifunctional additives, as purification components, have better compatibility with low molecular weight substances in the crude polypropylene product (such as unreacted raw materials remaining in the crude polypropylene product during polymerization and short-chain polymers generated). This allows for more effective removal of these low molecular weight substances, resulting in pharmaceutical-grade polypropylene products with advantages of low ash content and low precipitates, which is beneficial for industrial application.

[0016] Furthermore, the bifunctional additive is selected from one or more combinations of ethyl neopentanoyl acetate, methyl neopentanoyl acetate, methyl propionyl acetate, ethyl propionyl acetate, methyl butyryl acetate, and ethyl butyryl acetate. Wherein:

[0017] The structural formula of ethyl neopentanoyl acetate is:

[0018] The structural formula of neopentanoyl acetate methyl ester is:

[0019] The structural formula of methyl propionyl acetate is:

[0020] The structural formula of ethyl propionyl is:

[0021] The structural formula of methyl butyrylacetate is:

[0022] The structural formula of ethyl butyryl is:

[0023] Furthermore, the C5-C20 alkane solvent is selected from one or more combinations of n-hexane, n-heptane, n-octane, n-nonane, and n-decane.

[0024] In some alternative embodiments, the purifying agent is n-hexane and ethyl neopentanoyl, and the weight ratio of n-hexane to ethyl neopentanoyl is 2-13:1-2; or, the purifying agent is n-heptane and ethyl neopentanoyl, and the weight ratio of n-heptane to ethyl neopentanoyl is 2-10:1-3; or, the purifying agent is n-hexane and ethyl propionyl, and the weight ratio of n-hexane to ethyl propionyl is 2-9:1-3.

[0025] Furthermore, the purification temperature is 50–120°C, and the purification time is 0.5–3 h. Preferably, the purification temperature is 55–95°C, and the purification time is 0.5–2 h.

[0026] This invention does not impose any particular limitation on the method of propylene polymerization. The method of propylene polymerization includes, but is not limited to, one or a combination of two or more of the following: batch liquid phase bulk polymerization, loop liquid phase bulk polymerization, and gas phase fluidized bed production process. These polymerization processes are all conventional methods in the art, and those skilled in the art can choose according to their own operating conditions and required products, and will not be elaborated further here.

[0027] For example, in a preferred embodiment, the polymerization includes: mixing a first portion of propylene, a main catalyst, and a first portion of a co-catalyst for prepolymerization to obtain a prepolymer slurry; mixing a second portion of propylene, the prepolymer slurry, a second portion of the co-catalyst, an external electron donor, and hydrogen for liquid-phase bulk polymerization to obtain a first polymerization slurry; subjecting the first polymerization slurry to gas-phase polymerization to obtain a second polymerization slurry; subjecting the second polymerization slurry to gas-solid separation, and drying the solid phase component obtained from the gas-solid separation to obtain a crude polypropylene product.

[0028] Furthermore, in the prepolymerization process, the main catalyst, the first part of the co-catalyst, and the solvent (alkanes with 4 to 10 carbon atoms, such as n-hexane) are first mixed and fed into the prepolymerization reactor. Then, the first part of propylene is fed into the prepolymerization reactor, and the materials are stirred evenly by stirring inside the reactor to carry out the above-mentioned prepolymerization reaction. The prepolymerization includes a first stage and a second stage carried out sequentially: in the first stage, the prepolymerization temperature is -15 to 25°C, the propylene feeding rate is 10 to 45 kg / h, and the prepolymerization time is 0.5 to 3 h; in the second stage, the prepolymerization temperature is 5°C to 35°C, and the propylene feeding rate is 15 to 55 kg / h, until all the propylene for prepolymerization is added to the prepolymerization reactor.

[0029] Further, the second portion of propylene, the prepolymer slurry, the second portion of co-catalyst, the external electron donor, and hydrogen are added to a batch polymerization reactor for liquid-phase bulk polymerization. The third and fourth stages are carried out in two batch polymerization reactors connected in series, forming a fully mixed-flow multi-reactor series polymerization process. The liquid-phase bulk polymerization includes the third and fourth stages carried out sequentially: In the third stage, the polymerization temperature is 65–75°C, the polymerization pressure is 2.8–3.2 MPa, the hydrogen concentration is 1000–3000 ppm, and the product discharge melt flow rate is 3.5–4.5 g / 10 min; in the fourth stage, the polymerization temperature is 60–75°C, the polymerization pressure is 2.5–3.5 MPa, the hydrogen concentration is 1000–1500 ppm, and the product discharge melt flow rate is 3.0–4.0 g / 10 min.

[0030] Furthermore, the weight ratio of the main catalyst to propylene is 0.03–0.1 kg / t; the weight ratio of the co-catalyst to propylene is 0.12–0.25 kg / t; and the weight ratio of the external electron donor to the co-catalyst is 0–0.015 kg / kg.

[0031] Furthermore, the main catalyst of this invention exhibits an activity of 30,000 to 50,000 times greater than that of the catalyst in propylene polymerization. The specific calculation method is the mass ratio of the polymer obtained from the propylene polymerization catalyzed by the catalyst to the mass of the catalyst per unit time. The main catalyst of this invention is described in Chinese Patent 200910220352.7, which is also incorporated herein by reference. It is also commercially available.

[0032] Preferably, each of the above-mentioned main catalysts is an independent ZN series catalyst, comprising a MgCl2 support, a TiCl4 active center, and an internal electron donor; the internal electron donor is selected from one or more combinations of alkyl-substituted 1,3-diethers, aryl-substituted 1,3-diethers, succinates, malonic esters, and glycol esters. According to some specific embodiments of the present invention, the ZN series catalyst is the DJD-Z-1 catalyst from Liaoning Dingji.

[0033] The structure of alkyl-substituted 1,3-diethers is shown in formula (I).

[0034] In these aryl-substituted 1,3-diethers, the aryl group is selected from monocyclic or polycyclic C-terminal groups. 4-16 Aryl. More specifically, the aryl group of aryl-substituted 1,3-diethers is selected from cyclopentadienyl, indenyl, fluorenyl, and their derivatives. The structures of aryl-substituted 1,3-diethers are shown in formula (II) or formula (III).

[0035]

[0036] In equations (I), (II), and (III), R1, R2, R3, R4, R5, and R6 may be the same or different, and each is independently represented by C. 1-10 The alkyl group is a straight-chain or branched alkyl group. Preferably, R1, R2, R3, R4, R5, and R6 are the same or different, and each is independently methyl, ethyl, propyl, butyl, pentyl, heptyl, octyl, nonyl, or decyl.

[0037] The structures of succinates and malonic acid esters are shown in formula (IV) and formula (V), respectively:

[0038]

[0039] In equations (IV) and (V), R7, R8, R9, and R 10 Whether they are the same or different, each is independently C. 1-10Straight-chain or branched alkyl groups; more preferably, R7, R8, R9 and R 10 Each can be independently methyl, ethyl, propyl, butyl, pentyl, heptyl, octyl, nonyl, or decyl.

[0040] Furthermore, the cocatalyst of the present invention is an alkylaluminum compound, preferably a mixture of trialkylaluminum, trialkylaluminum and alkylaluminum halide or alkylaluminum hydride, or alkylaluminoxane, more preferably triethylaluminum.

[0041] Furthermore, the external electron donor is selected from one or more combinations of cyclohexyldimethoxymethylsilane, p-dicyclopentyldimethoxysilane, diisopropyldimethoxysilane, and diisobutyldimethoxysilane.

[0042] Furthermore, the product from the aforementioned fourth-stage batch polymerization reactor continues to enter a gas-phase fluidized bed reactor for gas-phase polymerization. During gas-phase polymerization, the polymerization temperature is 75–85°C, the polymerization pressure is 1.5–2.0 MPa, the melt flow rate of the polypropylene powder at the outlet of the gas-phase fluidized bed reactor is 2.8–3.4 g / 10 min, the ash content is less than 50 ppm, and the isotacticity is greater than 98.5%.

[0043] Furthermore, the material emanating from the gas-phase fluidized bed reactor first enters a cyclone separator for gas-solid separation. The solid component (polypropylene powder) enters a dryer where it is dried by convective inert gas at a temperature of 100–110°C. The gaseous portion is recycled into a recovery system. Nitrogen is preferred as the inert gas.

[0044] Further, the dried polypropylene powder is conveyed to a polymer deep purification tank using a conveying air system, and the aforementioned purification agent (C5-C20 alkane solvent and bifunctional group additive) is added to form a polymer powder slurry for purification. The slurry concentration is 10-40%, meaning the weight of the crude polypropylene product accounts for 10-40% of the total weight of the purification agent and the crude polypropylene product. Specifically, the weight of the crude polypropylene product ÷ (weight of C5-C20 alkane solvent + weight of bifunctional group additive + weight of crude polypropylene product) = 10-40%, preferably 15-30%. The purified product system is centrifuged to obtain a wet polymer powder, with a solvent content of 15-35 wt%. This wet polymer powder then undergoes a multi-stage drying process to remove volatile organic compounds, resulting in a solid purified product with an ash content of less than 10 ppm.

[0045] In a preferred embodiment, the dried solid component is mixed with an acid remover, a primary antioxidant, and a secondary antioxidant and then granulated to obtain pharmaceutical-grade polypropylene.

[0046] Furthermore, the deacidifying agent is selected from metal stearates and / or hydrotalcite; the weight ratio of the dried solid phase component to the deacidifying agent is 10000 to 20000:1.

[0047] Furthermore, the primary antioxidant is selected from one or more combinations of pentaerythritol tetrakis[β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate], 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)-S-triazine-2,4,6-(1H,3H,5H)trione, octadecyl β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene, and 1,1,3-tris(2-methyl-4-hydroxy-5-tert-butylphenyl)butane; the weight ratio of the dried solid phase component to the primary antioxidant is 200–10000:1.

[0048] Furthermore, the co-antioxidant is selected from one or more combinations of dilauryl thiodipropionate, dioctadecyl thiodipropionate, di(tetradecyl) thiodipropionate, trinonylphenyl phosphite, di(octadecyl)pentaerythritol diphosphite, tris(2,4-tert-butylphenyl) phosphite, and di(2,4-di-tert-butylphenyl)pentaerythritol diphosphite; the weight ratio of the dried solid phase component to the co-antioxidant is 500 to 10000:1.

[0049] Furthermore, a twin-screw extruder can be used for extrusion granulation. The resulting pharmaceutical-grade polypropylene has an ash content of less than 20 ppm, and the ash content introduced during granulation is ≤10 ppm.

[0050] This invention also provides a pharmaceutical-grade polypropylene, which is prepared by the aforementioned method for preparing pharmaceutical-grade polypropylene. Based on the reasons stated above, the pharmaceutical-grade polypropylene product of this invention has the advantages of low ash content and low precipitates, which is beneficial for industrial application. Detailed Implementation

[0051] In order to provide a clearer understanding of the technical features, objectives and beneficial effects of the present invention, the technical solution of the present invention will now be described in detail below, but it should not be construed as limiting the scope of implementation of the present invention.

[0052] Example 1

[0053] Prepolymerization:

[0054] Add 400 kg of n-hexane and 0.56 kg of triethylaluminum solution (including triethylaluminum and n-hexane, with a mass concentration of 15% in the triethylaluminum solution) to the catalyst preparation tank. Add 25 kg of DJD-Z-1 catalyst (a titanium metal main catalyst with magnesium chloride as the support) from Liaoning Dingjide Petrochemical Co., Ltd., and stir to form a uniform suspension. Use chilled brine to lower the temperature of the preparation tank to below 5°C, and then add 1000 kg of fresh n-hexane to adjust the concentration of the catalyst slurry. Start stirring at 80 r / min.

[0055] In the first stage of prepolymerization, the automatic propylene feeding valve in the gas phase is opened, the propylene feeding rate is adjusted to 10 kg / h, the stirring is started at 40 r / min, the temperature of the preparation tank is reduced to below -10℃, and prepolymerization is carried out for 1 hour. In the second stage of prepolymerization, the propylene feeding rate is adjusted to 15 kg / h, the stirring is started at 40 r / min, the temperature of the preparation tank is reduced to 10℃, and prepolymerization is carried out until all 200 kg of propylene is consumed, resulting in a propylene prepolymer slurry. The propylene prepolymer slurry is then transferred to a storage tank for later use.

[0056] Liquid-phase bulk polymerization:

[0057] The aforementioned propylene prepolymer slurry, propylene, triethylaluminum solution (including triethylaluminum and n-hexane, with a triethylaluminum mass concentration of 15%), cyclohexylmethyldimethoxysilane, and a suitable amount of hydrogen were added to the first batch reactor for liquid-phase bulk polymerization. Gaseous propylene was refluxed back into the reactor via a top condenser. The polymerization temperature was 70°C, the polymerization pressure was 3.0 MPa, the liquid level was 49%, the prepolymer slurry feed rate was 14.0 kg / h, the propylene feed rate was 5.7 t / h, the triethylaluminum solution feed rate was 0.8 kg / h, the cyclohexylmethyldimethoxysilane feed rate was 0.07 kg / h, and the hydrogen feed rate was 4.9 Nm³. 2 The hydrogen concentration is 2890 ppm. The outlet flow rate of the reaction slurry is 4.5 t / h.

[0058] The slurry from the first batch reactor enters the second batch reactor for polymerization. The temperature of the second batch reactor is 65℃, the polymerization pressure is 2.6MPa, and the liquid level is 44%. Hydrogen is added to the second batch reactor at a feed rate of 2.0 Nm³. 2 The hydrogen concentration is 1300 ppm. The outlet flow rate of the reaction slurry is 4.5 t / h.

[0059] Gas-phase polymerization:

[0060] The slurry from the outlet of the second batch reactor enters the gas-phase fluidized bed reactor for polymerization. The polymerization temperature is 82℃, the polymerization pressure is 1.8MPa, and the material level is 51%.

[0061] Polypropylene drying:

[0062] The material emanating from the gas-phase fluidized bed reactor first enters a cyclone separator for gas-solid separation. The separated solid polypropylene powder enters a dryer and is dried with convective nitrogen gas at a temperature of 105°C to obtain crude polypropylene product.

[0063] purification:

[0064] Crude polypropylene is transported to a polymer deep purification tank, where a certain amount of purifying agent (including n-hexane and ethyl neopentanoyl acetate in a weight ratio of 2:1) is added to form a polymer slurry. The mass concentration of crude polypropylene in the slurry is 10%. Deep purification of the polymer is carried out under specific process conditions (stirring speed 50 rpm, slurry feed rate 20 t / h), at a purification temperature of 65℃ for 1.5 h. The deeply purified polymer slurry is centrifuged to obtain a wet polymer powder with a solvent content of 25%. This powder then undergoes a multi-stage drying process (drying temperature 105℃) to remove volatile organic compounds, yielding the purified material.

[0065] Extrusion granulation:

[0066] The purified material is conveyed to the extrusion granulation unit, where a low-ash, long-lasting antioxidant composite additive (antioxidant 1010 is 2000 mg / kg, antioxidant 168 is 1000 mg / kg, and calcium stearate is 100 mg / kg) and the dried polypropylene powder are simultaneously added to a twin-screw extruder for extrusion granulation (granulation temperature is 225℃, screw speed is 120 rpm) to obtain low-ash, low-precipitation medical-grade polypropylene resin.

[0067] Example 2

[0068] The only difference from Example 1 is that the mass concentration of crude polypropylene in the slurry is 15%.

[0069] Example 3

[0070] The only difference from Example 1 is that the mass concentration of crude polypropylene in the slurry is 30%, and the purification temperature is 75°C.

[0071] Example 4

[0072] The only difference from Example 1 is that the purifying agent is n-heptane and ethyl neopentanoyl ester, the weight ratio of n-heptane to ethyl neopentanoyl ester is 5:3, the purification temperature is 80℃, and the purification time is 1h.

[0073] Example 5

[0074] The only difference from Example 1 is that the purifying agent is n-hexane and ethyl neopentanoyl ester, the weight ratio of n-hexane to ethyl neopentanoyl ester is 13:2, the purification temperature is 85℃, and the purification time is 1h.

[0075] Example 6

[0076] The only difference from Example 1 is that the purifying agent is n-hexane and ethyl neopentanoyl ester, the weight ratio of n-hexane to ethyl neopentanoyl ester is 1:2, the purification temperature is 80℃, and the purification time is 1h.

[0077] Example 7

[0078] The only difference from Example 1 is that the mass concentration of crude polypropylene in the slurry is 40%.

[0079] Example 8

[0080] The only difference from Example 1 is that the purification temperature is 50°C and the purification time is 3 hours.

[0081] Example 9

[0082] The only difference from Example 1 is that the purification temperature is 120°C and the purification time is 0.5 h.

[0083] Example 10

[0084] The only difference from Example 4 is that the purifying agent is n-heptane and ethyl neopentanoyl acetate, with a weight ratio of n-heptane to ethyl neopentanoyl acetate of 10:1.

[0085] Example 11

[0086] The only difference from Example 4 is that the purifying agent is n-heptane and ethyl neopentanoyl ester, with a weight ratio of n-heptane to ethyl neopentanoyl ester of 2:3.

[0087] Example 12

[0088] The only difference from Example 1 is that the purifying agent is n-hexane and ethyl propionate, with a weight ratio of n-hexane to ethyl propionate of 3:1.

[0089] Example 13

[0090] The only difference from Example 1 is that the purifying agent is n-hexane and ethyl propionate, with a weight ratio of n-hexane to ethyl propionate of 2:1.

[0091] Comparative Example 1

[0092] The only difference from Example 1 is that the purifying agent is ethyl acetoacetate.

[0093] Comparative Example 2

[0094] Prepolymerization:

[0095] The only difference from Example 1 is that the purifying agent is ethanol and the purification temperature is 45°C.

[0096] Comparative Example 3

[0097] The only difference from Example 1 is that the purifying agent is n-hexane and ethyl neopentanoyl ester, with a weight ratio of n-hexane to ethyl neopentanoyl ester of 119:1.

[0098] Comparative Example 4

[0099] The only difference from Example 1 is that the purifying agent is hexane and ethanol, the weight ratio of hexane to ethanol is 4:1, the mass concentration of crude polypropylene in the slurry is 30wt%, the purification temperature is 60℃, and the purification time is 0.5h.

[0100] Evaluation and analysis methods:

[0101] 1. Polymer ash content: Tested using inductively coupled plasma mass spectrometry.

[0102] The polypropylene sample to be tested was placed in a microwave digester, and 6 mL of concentrated nitric acid and 2 mL of hydrogen peroxide were added to completely digest it into a transparent solution. The volume was then adjusted to 50 mL, and the sample was analyzed using inductively coupled plasma mass spectrometry. The ash content of each element in the digestion solution was determined by referring to a standard curve and calculated using the following formula:

[0103]

[0104] In the formula: W—the ash content of metallic impurities in the polypropylene sample, μg / g (mass of a certain element / mass of polypropylene); ρ—the concentration of the element in the digestion solution, μg / mL; m—the mass of polypropylene weighed, g. The test results of the examples and comparative examples are shown in Table 1. The total ash content of the product is the sum of the metal oxides, obtained through calculation, as shown in Table 1.

[0105] Table 1

[0106]

[0107]

[0108] As shown in Table 1, when comparative examples 1 and 2 were washed with functional additives, the ash content of the resin products was reduced to 31.33 ppm and 33.27 ppm, respectively, indicating a moderate washing effect. When comparative examples 3 and 4 were washed with a composite additive consisting of hydrocarbons and functional additives, the ash content of the resin was reduced to only 26.61 ppm and 29.05 ppm due to the composition ratio of the composite solvent and the types of functional additives.

[0109] 2. Determination of precipitates: Following the standard YBB00112002—2015 Test Method for Leakage from Polypropylene Bottles for Oral Solid Pharmaceuticals, the sample was cut into small strips 5cm long and 0.3cm wide, with an inner surface area of ​​600cm². 2 The total surface area is 1200 cm². 2 (The area of ​​the side surfaces is not calculated). The provided sample was injection molded into 1.0 mm thick pieces at 230℃ using a granule injection molding machine. These pieces were then cut into small strips as required, totaling 400 strips. Each small strip was placed in a stoppered conical flask, an appropriate amount of water was added, and the pieces were shaken and washed. The water was discarded, and this process was repeated twice. After drying at 30–40℃, each strip was soaked in 200 mL of n-hexane (58℃±2℃) for 24 hours. After cooling to room temperature, the volume was replenished with solvent from the same batch of tests to prepare the test solution. The following tests were conducted using n-hexane as a blank solution. 50 mL of both the n-hexane test solution and the blank solution were accurately measured and placed in pre-weighed evaporating dishes. The mixture was evaporated to dryness in a water bath, dried at 105℃ for 2 hours, cooled, and accurately weighed. The difference between the non-volatile residue of the n-hexane solution and the residue of the blank solution was calculated. The test results of the examples and comparative examples are shown in Table 2 (the precipitate from the crude polypropylene product was 115 mg).

[0110] Table 2

[0111] Pharmaceutical grade polypropylene product precipitates (mg) Example 1 82 Example 2 76 Example 3 81 Example 4 79 Example 5 80 Example 6 87 Example 7 81 Example 8 93 Example 9 66 Example 10 79 Example 11 83 Example 12 95 Example 13 90 Comparative Example 1 109 Comparative Example 2 104 Comparative Example 3 102 Comparative Example 4 101

[0112] As shown in Table 2, when the polymers in Comparative Examples 1 and 2 were washed with functional additives alone, the content of polypropylene precipitates remained basically unchanged. However, when the polymers in Comparative Examples 3 and 4 were washed with a composite solvent composed of hydrocarbon solvents and functional additives such as ethyl pentanoyl acetate and ethanol, the washing effect was not as good as that of the composite solvent in Example 1 due to the differences in the composition, content, and types of functional additives of the composite solvent.

Claims

1. A method for preparing pharmaceutical-grade polypropylene, wherein, include: Propylene is polymerized to obtain crude polypropylene. The crude polypropylene product is sequentially purified, dried, and granulated to obtain the pharmaceutical-grade polypropylene. The purification agents used include C5-C20 alkane solvents and bifunctional additives having the structure shown in Formula I. In Formula I, R1 is a C2-C5 alkyl group, R2 is a C1-C3 alkylene group, and R3 is a C1-C4 alkyl group; The weight ratio of the hydrocarbon solvent to the bifunctional additive is 1-13:1-3.

2. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The purification temperature is 50–120°C.

3. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The purification time is 0.5 to 3 hours.

4. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The purification process is carried out at a temperature of 55–95°C for 0.5–2 hours.

5. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The bifunctional additive is selected from one or more of ethyl neopentanoyl acetate, methyl neopentanoyl acetate, methyl propionyl acetate, methyl butyryl acetate, and ethyl butyryl acetate.

6. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The C5-C20 alkane solvent is selected from one or more combinations of n-hexane, n-heptane, n-octane, n-nonane, and n-decane.

7. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The weight of the crude polypropylene product accounts for 10-40% of the total weight of the purifying agent and the crude polypropylene product.

8. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The aggregation includes: The first part of propylene, the main catalyst and the first part of the co-catalyst are mixed and prepolymerized to obtain a prepolymer slurry; The second portion of propylene, the prepolymer slurry, the second portion of cocatalyst, the external electron donor, and hydrogen are mixed and subjected to liquid-phase bulk polymerization to obtain the first polymer slurry; The first polymer slurry is subjected to gas-phase polymerization to obtain a second polymer slurry; The second polymer slurry is subjected to gas-solid separation, and the solid phase obtained from the gas-solid separation is dried to obtain the crude polypropylene product.

9. The method for preparing pharmaceutical-grade polypropylene according to claim 8, wherein, The external electron donor is selected from one or more of cyclohexyldimethoxymethylsilane, p-dicyclopentyldimethoxysilane, diisopropyldimethoxysilane, and diisobutyldimethoxysilane.

10. The method for preparing pharmaceutical-grade polypropylene according to claim 1, wherein, The ash content introduced during the granulation process is ≤10ppm.

11. A pharmaceutical-grade polypropylene, wherein, It is prepared by the method for preparing pharmaceutical-grade polypropylene according to any one of claims 1 to 10.

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