JP2007275255A - Propylene resin for medical syringe, medical syringe formed by injection-molding the same and prefilled syringe preparation - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide polypropylene resin composition having superior rigidity, heat resistance, transparency and impact resistance and attaining high productivity, and a medical instrument formed of the polypropylene resin composition. <P>SOLUTION: The polypropylene resin is composed of a propylene homopolymer having (i) a melt flow rate (ASTM D 1238, 230°C, 2.16 kg load) of 10-60 g/10 minutes, (ii) a meso pentad fraction (mmmm) of 0.920-0.950, and (iii) a molecular weight distribution (Mw/Mn) of 2.0-5.6, and not subjected to molecular weight reducing adjustment by a peroxide. This medical syringe is obtained by injection-molding the polypropylene resin, and this prefilled syringe preparation is obtained by filling the medical syringe with a medical solution with a pH of 5.0-9.0. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a prefilled syringe produced by injection molding using a polypropylene resin and filled with a chemical solution. More specifically, hygiene, heat resistance, suppression of bubble generation during molding and long run moldability, and further during injection molding ESCR with various types of medicines that have a pH level of 5.0 to 9.0, which is related to medical syringes that satisfy all requirements at the level at which damage to the core mold could not be achieved. The present invention relates to a prefilled syringe preparation that also considers impact resistance and drug stability.

  In recent years, a prefilled syringe preparation filled with a chemical solution has attracted attention for the purpose of reducing problems caused by an erroneous dosing process.

  In general, a prefilled syringe filled with a chemical solution is produced from glass or cyclic polyolefin, but its price is high and its market spread is not progressing. On the other hand, prefilled syringes using polypropylene resin are considered to be used because they are excellent in chemical properties, physical properties and moldability, and are inexpensive. However, the impact resistance of syringes due to interaction with the internal solution is being investigated. The current problem is that stable production has not been achieved due to cracking problems due to lowering and damage particularly when the core mold is removed during syringe molding. With the so-called conventional polypropylene resins described in Japanese Patent Nos. 3195434 and 2528443, mechanical strength, hygiene, transparency, long run productivity that suppresses syringe flaws at the time of pulling out the core mold during injection molding, and further when dropped Impact resistance has become a problem, there is no polypropylene resin that satisfies all of these problems, and it has been difficult to produce a prefilled syringe filled with a chemical solution that has solved all the problems.

If these demands can be realized by using inexpensive polypropylene resin, it can contribute to the widespread use of prefilled syringe preparations filled with chemicals, and has a very high degree of social contribution such as medical cost control for elderly patients.
Japanese Patent No. 3195434 Japanese Patent No. 2528443

  The present invention seeks to solve the problems associated with the prior art as described above, including hygiene, heat resistance, suppression of bubble generation during molding and long run moldability, and core mold extraction during injection molding. Provide a medical syringe that satisfies all requirements at a level that has not been able to achieve conventional scratch resistance, and is filled with various drugs whose pH of the inner solution is 5.0 to 9.0. It is a problem to provide an inexpensive prefilled syringe formulation that takes into account impact resistance and drug stability due to the phenomenon of impact resistance degradation and also referred to as environmental stress fracture resistance, and to provide further safety to the medical field To do.

[1] i) Melt flow rate (ASTM D 1238, 230 ° C., 2.16 kg load) is 10 to 60 g / 10 min, ii) Mesopentad fraction (mmmm) is 0.920 to 0.950, iii) Molecular weight distribution ( Mw / Mn) is made of a propylene homopolymer having a molecular weight of 2.0 to 5.6, and iii) is not subjected to molecular weight reduction adjustment treatment with peroxide, and is a polypropylene resin for medical syringes.
[2] A medical syringe obtained by injection molding the polypropylene resin according to [1].
[3] A prefilled syringe preparation, wherein the medical syringe according to [2] is filled with a chemical solution having a pH of 5.0 to 9.0.

  According to the present invention, hygiene, heat resistance, suppression of bubble generation during molding and long run moldability, as well as scratch resistance when extracting a core die during injection molding are all satisfied at a conventional level. In addition, a low-cost medical syringe has been completed, and various drugs with an internal solution pH of 5.0 to 9.0 have been filled, and the impact of ESCR and drug stability have been achieved. An inexpensive prefilled syringe formulation is obtained.

  Hereinafter, the polypropylene resin and its use according to the present invention will be specifically described.

  The polypropylene resin according to the present invention has an i) melt flow rate (MFR) (ASTM D 1238, 230 ° C., 2.16 kg load) of 10 to 60 g / 10 min, ii) a mesopentad fraction (mmmm) of 0.920 to 0 .950, iii) a propylene homopolymer having a molecular weight distribution (Mw / Mn) of 2.0 to 5.6, and iiii) a molecular weight reduction adjustment treatment with a peroxide is not performed.

   The polypropylene resin according to the present invention may be a single propylene homopolymer or a blend of two or more propylene homopolymers.

  The MFR of the propylene homopolymer according to the present invention is in the range of 10 to 60 g / 10 min. However, when the molecular weight distribution is 3.0 or more and 5.5 or less, it is preferably 15 to 40 g / 10 min. More preferably, it is 20-30 g / 10min. Moreover, when the molecular weight distribution is 2.0 or more and less than 3.0, it is particularly preferably 30 to 60 g / 10 minutes, more preferably 35 to 55 g / 10 minutes, and 40 to 45 g / 10 minutes. More preferably it is.

  When the MFR is in this range, it is possible to perform injection molding of a large number of medical syringes and to maintain impact resistance. If the MFR is not within this range, that is, if the MFR is less than 10, the injection molding of a large number of medical syringes cannot be performed, and the actual productivity is poor. If the MFR exceeds 60, the impact resistance is too low. Can not keep.

  In adjusting the MFR, which is a major feature of the present invention, it is important not to perform a molecular weight reduction adjustment process with a peroxide. When low molecular weight components and peroxide decomposition products generated by the peroxide weight reduction adjustment process are adsorbed to the mold during syringe production, the inner surface of the syringe is damaged, and the core mold is removed during injection molding. The scratching property is a problem.

  A method for confirming whether the polypropylene resin has deteriorated is as follows. Put the polypropylene resin in chloroform, extract it by ultrasonic cleaning for 60 minutes, and analyze by acetone and alcohols which are peroxide decomposition products by gas chromatographic analysis. It is possible by analyzing

  A preferable method for adjusting MFR other than degradation by peroxide is most effective in the hydrogen concentration and polymerization temperature in the polymerization, but MFR adjustment by a plurality of resin blends is also possible.

The mesopentad fraction (mmmm) measured by ¹³ C-NMR of the propylene homopolymer according to the present invention is 0.920 to 0.950, preferably 0.920 to 0.940.

  There are three advantages of setting the mesopentad fraction within this range, and one is a significant improvement in transparency. This can also suppress a decrease in transmittance after steam sterilization. The second is the impact resistance of the syringe. In syringe molding, since a cylindrical part is melted and molded, distortion and weld are likely to remain, and further distortion occurs due to flow orientation crystallization of polypropylene (solidifying while flowing). As a result, there is a problem that it is easily broken when an impact is applied. We have newly discovered that by setting the mesopentad fraction within this range, it is possible to significantly reduce the orientation crystallization of polypropylene, and to improve the impact resistance. The third point is that if it is significantly out of this range, the heat resistance of the syringe and the scratch resistance due to contact between the syringes become poor.

The mesopentad fraction (mmmm) indicates the abundance of isotactic chains in pentad units in a polypropylene molecular chain measured using ¹³ C-NMR. Specifically, the ratio of the absorption intensity (Pmmmm) derived from the methyl group at the center of the chain in which five meso-bonded propylene units are consecutive to the absorption intensity (Pw) derived from all the methyl groups in the propylene unit, that is, This is a value obtained as [(Pmmmm) / (Pw)]. The molecular weight distribution of the propylene homopolymer according to the present invention is 2.0 to 5.6, preferably 3.0 to 5.0.

  The method for adjusting the mesopentad fraction and the molecular weight distribution to the above ranges is described in detail in the Examples, but can be adjusted by the catalyst, the cocatalyst and the polymerization conditions.

  By limiting the molecular weight distribution to this range, there is an advantage that residual stress due to orientation crystallization can be reduced and contribution to impact resistance can be achieved.

  When the melt flow rate, the mesopentad fraction and the molecular weight distribution are all within the above ranges, the flowability (moldability) of the resulting polypropylene resin, transparency when used as a syringe, and particularly high impact resistance are obtained. In addition, it is possible to obtain a very good and highly functional syringe that is highly suppressed in scratches at the time of extraction of the core mold, which could not be obtained in the past, and that is rich in contents visibility.

The propylene homopolymer according to the present invention is produced by homopolymerizing propylene in the presence of a known titanium or metallocene polymerization catalyst and a co-catalyst. As the polymerization catalyst, for example, the polymerization catalyst described in WO01 / 27124 can be used. The polymerization process of the propylene homopolymer is usually at a temperature of about −50 to 200 ° C., preferably about 50 to 100 ° C., and usually at normal pressure to 100 kg / cm ² , preferably about ^{2 to} 50 kg / cm ² . Performed under pressure. The polymerization of propylene can be carried out by any of batch, semi-continuous and continuous methods.

  The polypropylene resin according to the present invention may contain a phosphorus-based antioxidant, an amine-based antioxidant, and a hydrochloric acid absorbent typified by hydrotalcite as necessary.

  There is no restriction | limiting in particular as phosphorus antioxidant, A conventionally well-known phosphorus antioxidant can be used. Note that it is preferable that only one type of phosphorus-based antioxidant is used because the content contamination due to bleeding is small. The phosphorus antioxidant is preferably a trivalent organic phosphorus compound, specifically, tris (2,4-di-t-butylphenyl) phosphite, 2,2-methylenebis (4,6-di-). t-butylphenyl) octyl phosphite, bis (2,6-di-t-butyl-4-methylphenyl) pentaerythritol diphosphite, and the like.

  The phosphorus-based antioxidant is usually 0.05 to 0.3 parts by weight, preferably 0.07 to 0.2 parts by weight, particularly preferably 0.1 to 0.15 parts by weight with respect to 100 parts by weight of the polypropylene resin. Used in parts ratio.

  Examples of amine-based antioxidants include compounds having a piperidine ring. Specifically, dimethyl succinate / 1- (2-hydroxyethyl) -4-hydroxy-2,2,6,6-tetramethylpiperidine polycondensate, bis (2,2,6,6-tetramethyl- 4-piperidyl) sebacate, poly [[6- [1-[(1,1,3,3-tetramethylbutyl) amino] -s-triazine-2,4-diyl] [[(2,2,6, 6-tetramethyl-4-piperidyl) imino] hexamethylene [(2,2,6,6-tetramethyl-4-piperidyl) imino]] and the like.

  The amine-based antioxidant is usually 0.01 to 0.3 parts by weight, preferably 0.01 to 0.2 parts by weight, more preferably 0.01 to 0.1 parts by weight with respect to 100 parts by weight of the polypropylene resin. Parts, particularly preferably 0.03-0.06 parts by weight.

  As the hydrochloric acid absorbent, hydrotalcite is preferable in consideration of the sterilization method, the formation of white turbidity with the chemical solution, and the interaction with the nucleating agent, but the fatty acid is suitably used only when there is no reactivity with the chemical solution. A combined system with hydrotalcite with the metal salt reduced as much as possible can also be used. The added amount of hydrochloric acid absorbent is 0.02 to 0.20 parts by weight with respect to 100 parts by weight of the polypropylene resin.

  If necessary, the polypropylene resin according to the present invention may further contain a heat resistance stabilizer, an antistatic agent, and a slip agent within the range not impairing the object of the present invention.

  In order to impart transparency to the polypropylene resin according to the present invention, a nucleating agent may be added. A general nucleating agent can be used as the nucleating agent. Adekastab NA-11 represented by organic phosphate ester is the most common. However, in order to satisfy the ultraviolet absorption spectrum which is the standard for plastic aqueous injection container (polyethylene or polypropylene injection container) of the 14th revised Japanese Pharmacopoeia General Test Method "Plastic Drug Container Test Method", sorbitol core Addition of agents is not desirable.

  The polypropylene resin according to the present invention contains a nucleating agent and other additives such as a phosphorus-based antioxidant, an amine-based antioxidant, a hydrochloric acid absorbent, etc., if necessary, with respect to the propylene homopolymer. After mixing using a V-type blender, tumbler blender, ribbon blender, etc., the above components and additives are uniform by melt-kneading using a single screw extruder, multi-screw extruder, kneader, Banbury mixer, etc. It can be obtained as a high-quality polypropylene resin composition dispersed and mixed.

  The medical syringe according to the present invention is obtained by injection molding the polypropylene resin. As a method for injection molding of polypropylene resin, a commonly used method can be used. By performing injection molding using the polypropylene resin, hygiene, heat resistance, suppression of bubble generation during molding and long run moldability, as well as scratchability when extracting a core die during injection molding can be achieved. It is possible to provide a medical syringe satisfying all at a level that has not been obtained.

  As for the chemical | medical solution used in the prefilled syringe chemical | medical agent which concerns on this invention, it is desirable that pH is 5.0-9.0. In the case of drugs with higher acidity or basicity than that, there is a risk that efficacy will be lost due to adsorption of chemical components to the syringe or interaction with a trace amount extract from the polypropylene resin composition during steam sterilization or long-term storage. There are undesirable.

  The chemical solution is not limited as long as it is in the above pH range, but for example, it is particularly desirable that the chemical solution be a neutral (pH around 7.0) such as a heparin aqueous solution or a potassium chloride aqueous solution. Highly volatile and high-concentration alcohol preparations are deformed due to an increase in syringe internal pressure during sterilization, and are excluded from chemical solutions regardless of pH.

  The prefilled syringe preparation according to the present invention is obtained by injection-molding a specific polypropylene resin, and further transparency that cannot be achieved in the past while maintaining rigidity, heat resistance, suppression of bubbles during molding, hygiene, and high cycle productivity. It has all of the balance that cannot be obtained with conventional polypropylene resins, such as excellent property improvement and impact resistance, and that the inner surface of the syringe is not easily damaged in long-run injection molding.

  EXAMPLES Next, although an Example demonstrates this invention, this invention is not limited at all by these Examples.

In Examples and the like, physical properties were measured by the following methods.
The melt flow rate (MFR) was measured at 230 ° C. and a load of 2.16 kg according to ASTM D 1238.
-Mesopentad fraction (mmmm) has shown the abundance ratio of the isotactic chain in the pentad unit in the polypropylene molecular chain measured using < ¹³ > C-NMR. Specifically, the ratio of the absorption intensity (Pmmmm) derived from the methyl group at the center of the chain in which five meso-bonded propylene units are consecutive to the absorption intensity (Pw) derived from all the methyl groups in the propylene unit, that is, [(Pmmmm) / (Pw)].
(3) The bending elastic modulus was subjected to a bending test according to ASTM D 790, and the bending elastic modulus was calculated from the result.
(4) Heat deformation temperature: It was performed according to ASTM D648. The unit is ° C.
(5) Transparency (visibility) evaluation: A square plate having a length of 12 cm, a width of 11 cm, and a thickness of 1 mm was injection-molded at 200 ° C. melting temperature / die temperature of 30 ° C., and the 14th revised Japanese Pharmacopoeia General Test Method “ According to the plastic water-based injection container (polyethylene or polypropylene-type injection container) of “Plastic drug container test method”, the syringe is steam sterilized for 1 hour at 121 ° C, and the parallel light transmittance in pure water before and after sterilization Was measured. The Japanese Pharmacopoeia standard is 55% or more in terms of parallel transmittance, but the product shape and thickness, especially in the case of syringes are designed with a thickness of 1 mm to 1.2 mm, with 55% being 1 mm and 1.2 mm. Assuming the case of wall thickness, 66% or more, which is 20% of 55% of 1 mm, was set as a pass criterion, and X was set as a parallel transmitted light rate of 65% or less.
(6) As an evaluation of moldability, a syringe production cycle time (seconds) was determined with a 150-ton electric injection molding machine using a 20 ml, 1 mm-thick syringe outer mold with a thickness of 1 mm. It was.

  In addition, 200 shots were produced, and the case where the core mold was removed from the inner surface of the syringe was marked with ×, and the case without scratch was marked with ○.

As will be described later, those that could not be molded due to low MFR were marked as unmoldable.
(7) Using the above syringe, heparin (500 u / ml) aqueous solution was put into a pusher, and the deformation of the syringe after steam sterilization at 121 ° C. for 1 hour was evaluated visually.
(8) Syringe breaking height is 45 g of square weight dropped on the syringe barrel at various heights, and the average breaking height (n = 10) is determined. did.

[Production Example 1]
[Preparation of solid titanium catalyst component (a)]
952 g of anhydrous magnesium chloride, 4420 ml of decane and 3906 g of 2-ethylhexyl alcohol were heated at 130 ° C. for 2 hours to obtain a homogeneous solution. To this solution, 213 g of phthalic anhydride was added, and further stirred and mixed at 130 ° C. for 1 hour to dissolve phthalic anhydride.

After cooling the homogeneous solution thus obtained to 23 ° C., 750 ml of this homogeneous solution was dropped into 2000 ml of titanium tetrachloride maintained at −20 ° C. over 1 hour. After the dropwise addition, the temperature of the resulting mixture was raised to 110 ° C. over 4 hours. When the temperature reached 110 ° C., 52.2 g of diisobutyl phthalate (DIBP) was added, and the mixture was stirred at the same temperature for 2 hours. Held on. Subsequently, the solid part was collected by hot filtration, and the solid part was resuspended in 2750 ml of titanium tetrachloride, and then heated again at 110 ° C. for 2 hours.
After the heating, the solid part was again collected by hot filtration, and washed with decane and hexane at 110 ° C. until no titanium compound was detected in the washing solution.
The solid titanium catalyst component (a) prepared as described above was stored as a hexane slurry. A part of the catalyst was dried to examine the catalyst composition. The solid titanium catalyst component (a) contained 3% by weight of titanium, 58% by weight of chlorine, 18% by weight of magnesium and 21% by weight of DIBP.

[Preparation of prepolymerization catalyst]
In a 200 liter autoclave equipped with a stirrer, under a nitrogen atmosphere, 140 liters of purified heptane, 0.28 mol of toluethylaluminum, and 0.094 mol of the solid titanium catalyst component (a) obtained above were charged in terms of titanium atoms. Thereafter, 1350 g of propylene was introduced and reacted for 1 hour while maintaining the temperature at 20 ° C. or lower.
After completion of the polymerization, the inside of the reactor was replaced with nitrogen, and the supernatant was removed and washed with purified heptane three times. The obtained prepolymerized catalyst was resuspended in purified heptane, transferred to a catalyst supply tank, and adjusted with purified heptane so that the solid titanium catalyst component (a) concentration was 1.5 g / L. This prepolymerized catalyst contained 6 g of polypropylene per 1 g of the solid titanium catalyst component (a).

[polymerization]
While charging 300 liters of liquefied propylene into a polymerization tank 1 with a stirrer having an internal volume of 500 liters and maintaining this liquid level, 130 kg / h of liquefied propylene, 1.7 g / h of the prepolymerized catalyst, 42 mmol / h of triethylaluminum, Cyclohexylmethyldimethoxysilane (6.3 mmol / h) and normal butylmethyldimethoxysilane (0.7 mmol / h) were continuously supplied, and polymerization was performed at a temperature of 75 ° C. Hydrogen 220 NL / h was supplied. The obtained slurry was deactivated, and then sent to a liquid propylene washing tank, and the polypropylene powder was washed. Thereafter, propylene was evaporated to obtain polypropylene powder (A1).
This composition had an MFR of 20 g / 10 min, a mesopentad fraction (mmmm) of 0.950, and Mw / Mn of 5.2.

[Production Example 2]
300 liters of liquefied propylene was charged into a polymerization tank 1 with a stirrer having an internal volume of 500 liters, and while maintaining this liquid level, 130 kg / h of liquefied propylene, 1.9 g / h of the same prepolymerization catalyst as in Production Example 1, triethylaluminum 50 mmol / h, cyclohexylmethyldimethoxysilane 3.9 mmol / h, and normalbutylmethyldimethoxysilane 4.4 mmol / h were continuously supplied, and polymerization was performed at a temperature of 75 ° C. Further, hydrogen was supplied at 170 NL / h. The obtained slurry was deactivated, and then sent to a liquid propylene washing tank, and the polypropylene powder was washed. Thereafter, propylene was evaporated to obtain polypropylene powder (A2).
This composition had an MFR of 20 g / 10 min, a mesopentad fraction (mmmm) of 0.935, and Mw / Mn of 5.1.

[Production Example 3]
300 liters of liquefied propylene was charged into a polymerization tank 1 with a stirrer having an internal volume of 500 liters, and while maintaining this liquid level, 130 kg / h of liquefied propylene, 2.0 g / h of the same prepolymerization catalyst as in Production Example 1, triethylaluminum 55 mmol / h, cyclohexylmethyldimethoxysilane 1.8 mmol / h, and normal butylmethyldimethoxysilane 7.3 mmol / h were continuously supplied, and polymerization was performed at a temperature of 75 ° C. In addition, hydrogen was supplied at 115 NL / h. The obtained slurry was deactivated, and then sent to a liquid propylene washing tank, and the polypropylene powder was washed. Thereafter, propylene was evaporated to obtain polypropylene powder (A3).
This composition had an MFR of 20 g / 10 min, a mesopentad fraction (mmmm) of 0.920, and Mw / Mn of 5.1.

[Production Example 4]
[Preparation of solid catalyst support]
300 g of SiO ₂ (manufactured by Dokai Chemical Co., Ltd.) was sampled in a 1 L branch flask, and 800 mL of toluene was added to make a slurry. Next, the solution was transferred to a 5 L four-necked flask, and 260 mL of toluene was added. 2830 mL of methylaluminoxane (hereinafter referred to as MAO) -toluene solution (Albemarle 10 wt% solution) was introduced. The mixture was stirred for 30 minutes while remaining at room temperature. The temperature was raised to 110 ° C. over 1 hour and the reaction was carried out for 4 hours. After completion of the reaction, it was cooled to room temperature. After cooling, the supernatant toluene was extracted and replaced with fresh toluene until the replacement rate reached 95%.
[Preparation of solid catalyst component (b) (support of transition metal compound component on support)]
In a glove box, 2.0 g of diphenylmethylene (3-t-butyl-5-methylcyclopentadienyl) (2,7-di-t-butylfluorenyl) zirconium dichloride was weighed in a 5 L four-necked flask. . The flask was taken out, 0.46 liters of toluene and 1.4 liters of MAO / Si, SiO2 / toluene slurry prepared in the production of the solid catalyst support were added under nitrogen, and the mixture was stirred for 30 minutes to carry. The resulting diphenylmethylene (3-t-butyl-5-methylcyclopentadienyl) (2,7-t-butylfluorenyl) zirconium dichloride / MAO / SiO ₂ / toluene slurry was 99% in normal-heptane. Substitution was performed and the final slurry volume was 4.5 liters. This operation was performed at room temperature.

(Prepolymer production)
189 g of the above-mentioned solid catalyst component (b), 99.5 mL of triethylaluminum, and 94.5 L of heptane were inserted into an autoclave equipped with a stirrer with an internal volume of 200 L, maintained at an internal temperature of 15 to 20 ° C., 2640 g of ethylene were inserted, and stirred for 180 minutes. It was made to react. After completion of the polymerization, the solid component was precipitated, and the supernatant was removed and washed with heptane twice. The obtained prepolymer was resuspended in purified heptane and adjusted with heptane so that the solid catalyst component concentration was 2 g / L. A part was sampled and the prepolymer was analyzed. This prepolymer, that is, the prepolymerization catalyst, contained 10 g of polyethylene per 1 g of the solid catalyst component (b).
[Prepolymer production]
Propylene 45 kg / h, hydrogen 12 NL / h, 2.5 g / h of the catalyst slurry produced above as solid catalyst component (b), 1.5 g / h of triethylaluminum continuously in a tubular polymerizer with an internal volume of 58 L And polymerized in a full liquid state without a gas phase. The temperature of the tubular reactor was 30 ° C., and the pressure was 2.8 MPa / G.

[Main polymerization]
The slurry obtained by the pre-polymerization was sent to a vessel polymerization vessel with a stirrer having an internal volume of 1000 L, and further polymerization was performed. To the polymerization reactor, propylene was supplied at 50 kg / h, and hydrogen was supplied so that the hydrogen concentration in the gas phase was 0.45 mol%. Polymerization was performed at a polymerization temperature of 70 ° C. and a pressure of 2.7 MPa / G.
The obtained slurry was sent to a vessel polymerization vessel with a stirrer having an internal volume of 500 L, and further polymerization was performed. To the polymerization reactor, propylene was supplied at 30 kg / h, and hydrogen was supplied so that the hydrogen concentration in the gas phase was 0.5 mol%. Polymerization was performed at a polymerization temperature of 68 ° C. and a pressure of 2.7 MPa / G.
After vaporizing the resulting slurry, gas-solid separation was performed to obtain propylene polymer particles (A4). The resulting propylene polymer particles were vacuum dried at 80 ° C.
This composition had MFR40, a mesopentad fraction (mmmm) of 0.950, and Mw / Mn of 2.0.

[Production Example 5]
While charging 300 liters of liquefied propylene into a polymerization tank 1 with an internal volume of 500 liters while maintaining this liquid level, 130 kg / h of liquefied propylene, 2.1 g / h of the same prepolymerization catalyst as in Production Example 1, triethylaluminum 58 mmol / h, cyclohexylmethyldimethoxysilane 0.2 mmol / h, and normal butylmethyldimethoxysilane 9.5 mmol / h were continuously fed and polymerized at a temperature of 75 ° C. Hydrogen was supplied at 50 NL / h. The obtained slurry was deactivated, and then sent to a liquid propylene washing tank, and the polypropylene powder was washed. Thereafter, propylene was evaporated to obtain polypropylene powder (A5). This composition had an MFR of 20 g / 10 min, a mesopentad fraction (mmmm) of 0.910, and Mw / Mn of 5.1.

[Production Example 6]
While charging 300 liters of liquefied propylene into a polymerization tank 1 with a stirrer having an internal volume of 500 liters and maintaining this liquid level, 130 kg / h of liquefied propylene, 1.5 g / h of the same prepolymerization catalyst as in Production Example 1, triethylaluminum 38 mmol / h, 6.3 mmol / h of dicyclopentyldimethoxysilane were continuously supplied, and polymerization was performed at a temperature of 75 ° C. Hydrogen 230 NL / h was supplied. The obtained slurry was deactivated, and then sent to a liquid propylene washing tank, and the polypropylene powder was washed. Thereafter, propylene was evaporated to obtain polypropylene powder (A6).
This composition had an MFR of 20 g / 10 min, a mesopentad fraction (mmmm) of 0.960, and Mw / Mn of 5.6.

[Production Example 7]
(1) Preparation of solid catalyst component (B) 160 g (1.4 mol) of diethoxymagnesium was added to a 5-necked three-necked flask with an internal volume substituted with nitrogen and 500 ml of dehydrated heptane was added. added. The mixture was heated to 40 ° C., 28.5 ml (225 mmol) of silicon tetrachloride was added, stirred for 20 minutes, and 127 mmol of diethyl phthalate was added. The temperature of the solution was raised to 80 ° C., and subsequently 461 ml (4.2 mol) of titanium tetrachloride was added dropwise using a dropping funnel. The internal temperature was set to 110 ° C. and the mixture was stirred for 2 hours to carry out the supporting operation. Thereafter, it was thoroughly washed with dehydrated heptane. Further, 768 ml (7 moles) of titanium tetrachloride was added, the internal temperature was set to 110 ° C., and the mixture was stirred for 2 hours to carry out the second loading operation. Thereafter, the solid component (B) was obtained by sufficiently washing with dehydrated heptane. (2) Prepolymerization of solid catalyst A heptane slurry containing 60 g (37.6 mmol-Ti) of the above solid titanium catalyst component was charged into a three-necked flask equipped with a stirrer with an internal volume of 1 liter substituted with nitrogen, Further, dehydrated heptane was added to make a total volume of 500 ml. This was stirred while controlling at 40 ° C., and 24.8 mmol of triethylaluminum and 6.2 mmol of cyclohexyldimethoxysilane were added. While maintaining the temperature at 40 ° C., a predetermined amount of propylene was absorbed for 120 minutes, and the remaining propylene was replaced with nitrogen, and washed thoroughly with heptane to obtain 85 grams of a prepolymerized catalyst component (B) (seal amount: 0.00). 43 grams-PP / gram solid Ti catalyst component). (3) Propylene Slurry Polymerization A stainless steel autoclave with a stirrer with an internal volume of 10 liters was sufficiently dried, and after substitution with nitrogen, 6 liters of dehydrated heptane was added. The autoclave temperature was warmed to 80 ° C. and 12 mmol of triethylaluminum was added followed by 1.2 mmol of cyclohexylmethyldimethoxysilane. Next, 0.02 MPa of hydrogen was introduced, and then propylene was introduced to bring the total pressure to 0.78 MPa. After the system was stabilized, 0.3 mmol of the prepolymerized catalyst component per Ti was added to start the polymerization. After 1 hour, 50 ml of methanol was charged into the system to complete the polymerization, and the temperature was lowered and the pressure was released. Subsequently, the solid part was taken out, filtered and dried in vacuum. As a result, 2.4 kg of a propylene polymer (A7) was obtained. The intrinsic viscosity [η] of this polymer measured in 135 ° C. tetralin was 1.49 dl / g. The MFR measured in accordance with JIS K7210 was 20.0 g / 10 min, the mesopentad fraction (mmmm) was 0.927, and Mw / Mn was 5.8.

[Production Example 8]
Prepolymerization A three-necked flask equipped with a stirrer with an internal volume of 5 liters was thoroughly dried and replaced with nitrogen gas. Then, 4 liters of dehydrated heptane and 140 grams of diethylaluminum chloride were added to add a solid catalyst component (A) (commercially available 20 g of Solvay type titanium trichloride catalyst (manufactured by Tosoh Finechem) was added. The internal temperature was kept at 20 ° C., and propylene was continuously introduced while stirring. After 80 minutes, stirring was stopped, and as a result, a prepolymerized catalyst component (A) in which 0.8 g of propylene was polymerized per 1 g of the solid catalyst was obtained. (2) Propylene polymerization A stainless steel autoclave with a stirrer with an internal volume of 10 liters was sufficiently dried and replaced with nitrogen gas, 6 liters of dehydrated heptane was added, and nitrogen in the system was replaced with propylene. Thereafter, propylene was introduced while stirring by adding 0.14 MPa of hydrogen at an internal temperature of 60 ° C. After the system was stabilized at a total pressure of 0.78 MPa and 60 ° C., 150 ml of heptane slurry containing 0.75 grams of the prepolymerized catalyst component in terms of solid catalyst was added to initiate polymerization. After continuously supplying propylene for 4 hours from the start of polymerization, 50 ml of methanol was added to complete the polymerization, and the temperature was lowered and the pressure was released. The entire contents were transferred to a filtration tank with a filter, 100 ml of 1-butanol was added, and the mixture was stirred at 85 ° C. for 1 hour, followed by solid-liquid separation. Further, the solid part was washed twice with a mixed solution of 5 liters of heptane at 85 ° C. and 1 liter of distilled water, and vacuum dried. As a result, 3.5 kg of a propylene polymer (A8) was obtained. The intrinsic viscosity [η] of this polymer measured in 135 ° C. tetralin was 1.42 dl / g. The MFR measured in accordance with JIS K7210 was 20.7 g / 10 min, the mesopentad fraction (mmmm) was 0.940, and Mw / Mn was 8.4.

  The propylene polymer (A10) and the propylene polymer (A11) were produced by adjusting the amount of hydrogen in Production Example 6.

[Production Example 9]
300 liters of liquefied propylene was charged into a polymerization tank 1 with a stirrer having an internal volume of 500 liters, and while maintaining this liquid level, 130 kg / h of liquefied propylene, 1.4 g / h of prepolymerized catalyst, 35 mmol / h of triethylaluminum, cyclohexyl Methyldimethoxysilane (5.2 mmol / h) and normal butylmethyldimethoxysilane (0.6 mmol / h) were continuously supplied, and polymerization was performed at a temperature of 75 ° C. Hydrogen 240 NL / h and ethylene 2 kg / h were supplied. The obtained slurry was deactivated, and then sent to a liquid propylene washing tank, and the polypropylene powder was washed. Thereafter, propylene was evaporated to obtain polypropylene powder (A12).
This composition had MFR 20 g / 10 min, ethylene content 2.3 wt%, and Mw / Mn 5.6.

The raw materials used in the examples and the physical property values are as follows.
Propylene homopolymer (A1)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.950.
Mw / Mn = 5.2.
Propylene homopolymer (A2)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.935.
Mw / Mn = 5.1.
Propylene homopolymer (A3)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.920.
Mw / Mn = 5.1.
Propylene homopolymer (A4)
Melt flow rate: 40 g / 10 min, mesopentad fraction: 0.950.
Mw / Mn = 2.0.
Propylene homopolymer (A5)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.910.
Mw / Mn = 5.1.
Propylene homopolymer (A6)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.960.
Mw / Mn = 5.6.
Propylene homopolymer (A7)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.927.
Mw / Mn = 5.8.
Propylene homopolymer (A8)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.940.
Mw / Mn = 8.4.
Propylene homopolymer (A9)
Melt flow rate: 20 g / 10 min, mesopentad fraction: 0.930.
Mw / Mn = 4.1.
Propylene homopolymer (A10)
Melt flow rate: 5 g / 10 min, mesopentad fraction: 0.920.
Mw / Mn = 5.6.
Propylene homopolymer (A11)
Melt flow rate: 65 g / 10 min, mesopentad fraction: 0.920.
Mw / Mn = 5.6.
Ethylene-propylene random copolymer (A12)
Melt flow rate: 20 g / 10 min, ethylene content: 2.3 wt%, Mw / Mn = 5.6.

Nucleator (B)
Sodium-2,2-methylenebis (4,6-di-t-butylphenyl) phosphate (trade name, Adeka Stub NA-11UY, manufactured by Adeka).
Phosphorous antioxidant (C)
Tris (2,4-di-t-butylphenyl) phosphite (trade name: Irgaphos 168, manufactured by Ciba Specialty Chemicals).
Amine-based antioxidant (D)
Dimethyl succinate / 1- (2-hydroxyethyl) -4-hydroxy-2,2,6,6-tetramethylpiperidine polycondensate (manufactured by Ciba Specialty Chemicals, trade name Tinuvin 622LD).
Hydrochloric acid absorbent (E)
Hydrotalcite represented by Mg ₄ Al ₂ (OH) ₁₂ CO ₃ .3H ₂ 0 (Kyowa Chemical Co., Ltd., trade name DHT-4A).
Peroxide (F)
2,5-dimethyl-2,5-di (t-butylperoxy) hexane (manufactured by NOF Corporation, trade name: Perhexa 25B).

100 parts by weight of a propylene homopolymer (A1) is supplied into a Henschel mixer, and further, 0, 10 parts by weight of the nucleating agent (B), 0.10 parts by weight of a phosphorus antioxidant (C), an amine-based oxidation 0.04 part by weight of inhibitor (D) and 0.03 part by weight of hydrochloric acid absorbent (E) were added and mixed with stirring.
Next, the obtained mixture was melt-kneaded at a resin temperature of 200 ° C. using a tandem machine of a high speed twin screw extruder CIM50S and a single screw extruder P65EXT (65 mmφ) manufactured by Nippon Steel Works, and the kneaded product was extruded and water tank Was cooled and cut to obtain polypropylene resin composition pellets. Next, using the pellets, a sheet-shaped test piece having a thickness of 2 mm at 200 ° C. and a mold temperature of 40 ° C. by injection molding, a test piece for bending strength test (ASTM D 790, thickness 3.2 mm, length 127 mm, And a test piece (ASTM D 648, thickness 4.0 mm, length 127 mm, width 12.7 mm) for the heat deformation temperature test.
Using these test pieces, measurement was performed according to the method described above. These results are shown in Table 1.

  In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A2). The physical property measurement results are shown in Table 1.

  In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A3). The physical property measurement results are shown in Table 1.

  In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A4). The physical property measurement results are shown in Table 1.

[Comparative Example 1]
In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A5). The physical property measurement results are shown in Table 1.

[Comparative Example 2]
In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A6). The physical property measurement results are shown in Table 1.

[Comparative Example 3]
In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A7). The physical property measurement results are shown in Table 1.

[Comparative Example 4]
In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A8). The physical property measurement results are shown in Table 1.

[Comparative Example 5]
The propylene homopolymer (A9) was used by adjusting the melt flow rate by the molecular weight reduction adjustment treatment with peroxide as follows.
100 parts by weight of a propylene homopolymer powder having an MFR of 2 g / 10 min, a mesopentad fraction: 0.930, and Mw / Mn = 5.1 was fed into a Henschel mixer, and the nucleating agent (B) 0, 10 parts by weight, phosphorus antioxidant (C) 0.10 parts by weight, amine antioxidant (D) 0.04 parts by weight, hydrochloric acid absorbent (E) 0.03 parts by weight, peroxide (F) 0.04 part by weight was added and mixed with stirring.
Subsequently, the obtained mixture was melt kneaded at a resin temperature of 200 ° C. using a tandem machine of a high speed twin screw extruder CIM50S manufactured by Nippon Steel Works and a single screw extruder P65EXT (65 mmφ), the kneaded product was extruded, The pellet (A9) of a polypropylene resin composition was obtained by cooling and cutting at. This composition had a melt flow rate of 20 g / 10 min, a mesopentad fraction: 0.930, and Mw / Mn = 4.1. Then, using the pellets, a sheet-shaped test piece having a thickness of 2 mm at 200 ° C. and a mold temperature of 40 ° C. by injection molding as in Example 1, a test piece for bending strength test (ASTM D 790, thickness 3.2 mm). , 127 mm in length, 12.7 mm in width), and a test piece (ASTM D 648, thickness 4.0 mm, length 127 mm, width 12.7 mm) for heat deformation temperature test.
Using these test pieces, measurement was performed according to the method described above. These results are shown in Table 1.

[Comparative Example 6]
In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A10). The physical property measurement results are shown in Table 1.

[Comparative Example 7]
In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the propylene homopolymer (A11). The physical property measurement results are shown in Table 1.

[Comparative Example 8]
In Example 1, it carried out like Example 1 except having changed the propylene homopolymer (A1) into the ethylene-propylene random copolymer (A12). The physical property measurement results are shown in Table 1.

  From the physical property measurement results shown in Table 1, with a highly controlled polypropylene resin according to the present invention, the molded product (medical syringe) has a balance of transparency, impact resistance and rigidity, and hygiene that could not be achieved conventionally. In addition, it satisfied all of the heat resistance, suppression of bubble generation during molding, long run moldability, and scratch resistance when removing the core mold during injection molding.

  It has been found that, for the first time, all of the necessary physical properties of all of these syringes can be satisfied by not adjusting the molecular weight of the narrow propylene homopolymer composition and peroxide.

  Moreover, this medical syringe was filled with various chemicals having a pH of the internal solution of 5.0 to 9.0 to obtain a prefilled syringe preparation that also achieved chemical stability.

When this resin composition is used, it does not use other expensive auxiliary materials, greatly contributes to the marketability of prefilled syringes using drugs with low drug prices, and greatly contributes to the safe medical field. It can be expected to penetrate into the market in the future, and it is very useful because it has improved safety such as misuse and breakage at medical sites and visibility of internal solution.

Claims (3)

Melt flow rate (ASTM D 1238, 230 ° C., 2.16 kg load) is 10 to 60 g / 10 min, ii) Mesopentad fraction (mmmm) is 0.920 to 0.950, iii) Molecular weight distribution (Mw / Mn) is A polypropylene resin for medical syringes, characterized in that it comprises a propylene homopolymer of 2.0 to 5.6 and iiii) is not subjected to molecular weight reduction adjustment treatment with peroxide. A medical syringe obtained by injection molding of the polypropylene resin according to claim 1. A prefilled syringe preparation, wherein the medical syringe according to claim 2 is filled with a chemical solution having a pH of 5.0 to 9.0.