Description:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)

1. TITLE OF THE INVENTION:
METHOD TO PREPARE RESORBABLE POLYMER

2. APPLICANTS:
Meril Endosurgery Pvt. Ltd., an Indian company, of the address Survey No. 135/139 Bilakhia House, Muktanand Marg, Chala, Vapi- 396191, Gujarat

The following specification particularly describes the invention and the manner in which it is to be performed:

 
FIELD OF INVENTION
[001] The present disclosure relates to a method to prepare polymers. More specifically, the present disclosure relates to a method for preparing a resorbable polymer.
BACKGROUND OF INVENTION
[002] Suture is one of the indispensable medical tools for an exploratory medical procedure and treating a flesh wound. A needle or the like is used to pull the suture across the tissue, thereby, sewing the tissues together. The suture is made of a polymeric material that gradually breaks down (i.e., biodegrades/resorbs) into two or more non-toxic byproducts after a certain period of time.
[003] However, the method to manufacture conventional polymeric material used for making a suture, suffers from a few drawbacks. For example, the conventional method requires a very long time for annealing the polymer, i.e., drying the polymeric material, to remove unreacted monomers. Furthermore, the conventional method has a high chance of forming residual monomers while preparing the polymeric material and even higher chance of undergoing backbiting reaction to form undesirable by-products.
[004] Thus, there arises a need for a method of preparation thereof that overcomes the drawbacks of the conventionally available solutions.
SUMMARY OF INVENTION
[005] Particular embodiments of the present disclosure are described herein below with reference to the accompanying drawings; however, it is to be understood that the disclosed embodiments are mere examples of the disclosure, which may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure.
[006] The present disclosure relates to a method to prepare resorbable polymer. The method commences by adding a predefined amount of a first monomer, a pre-defined amount of a second monomer, a pre-defined amount of an imitator, and a pre-defined amount of catalyst in a vessel to obtain a reaction mixture. The quantity of the second monomer being more than the quantity of the first monomer. The vessel has a circulation of a pre-defined inert gas. The reaction mixture is subjected to heating thereby, polymerizing the first monomer and the second monomer to obtain the resorbable polymer. The vessel is swept for one or more cycles to remove any unreacted second monomer. Each cycle includes creating a vacuum inside the vessel for a pre-defined amount of time, holding the vacuum inside the vessel for a pre-defined amount of time, and purging the inert gas inside the vessel for a pre-defined amount of time. The resorbable polymer is cooled. The resorbable polymer is annealed for a pre-defined amount of time to remove any unreacted second monomer. The pre-defined amount of time ranging from 2 hours to 24 hours.
BRIEF DESCRIPTION OF DRAWING
[007] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the apportioned drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the disclosure is not limited to specific methods and instrumentality disclosed herein. Moreover, those in the art will understand that the drawings are not to scale.
[008] Fig. 1 depicts a method 100 for preparation of a resorbable polymer, according to an embodiment of the present disclosure.
[009] Fig. 2 depicts a side view of an apparatus 200 for preparing the resorbable polymer, according to an embodiment of the present disclosure.
[0010] Fig. 2a depicts a longitudinal cross-sectional view of the apparatus 200 from the front, according to an embodiment of the present disclosure.
[0011] Fig. 3 depicts a side view of a cooling tunnel 300 to cool the resorbable polymer, according to an embodiment of the present disclosure.
DETAILED DESCRIPTION OF THE INVENTION
[0012] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have a property of, or the like. Definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases.
[0013] Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment, but mean “one or more but not all embodiments” unless expressly specified otherwise. The terms “including,” “comprising,” “having,” and variations thereof mean “including but not limited to” unless expressly specified otherwise. An enumerated listing of items does not imply that any or all of the items are mutually exclusive and/or mutually inclusive, unless expressly specified otherwise. The terms “a,” “an,” and “the” also refer to “one or more” unless expressly specified otherwise.
[0014] Although the operations of exemplary embodiments of the disclosed method may be described in a particular, sequential order for convenient presentation, it should be understood that the disclosed embodiments can encompass an order of operations other than the particular, sequential order disclosed. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular embodiment are not limited to that embodiment, and may be applied to any embodiment disclosed herein. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed system, method, and apparatus can be used in combination with other systems, methods, and apparatuses.
[0015] Furthermore, the described features, advantages, and characteristics of the embodiments may be combined in any suitable manner. One skilled in the relevant art will recognize that the embodiments may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments. These features and advantages of the embodiments will become more fully apparent from the following description and apportioned claims, or may be learned by the practice of embodiments as set forth hereinafter.
[0016] The present disclosure relates to a method to prepare a resorbable polymer (or polymeric material). The resorbable polymer includes at least a first monomer and a second monomer copolymerized in a pre-defined ratio to form a copolymer. In an exemplary embodiment, the first monomer is lactic acid (LA) and the second monomer is glycolic acid (GA) copolymerized at a ratio by mole of 10:90 to form Poly(lactic-co-glycolic acid) (PLGA/PGLA). The resorbable polymer may be used for making sutures, drug delivery systems, scaffolds for tissue engineering, etc.
[0017] The resorbable polymer is made of two monomers, i.e., a first monomer and a second monomer. The polymerization of the monomers is carried out in the presence of an initiator and a catalyst via a ring opening polymerization technique.
[0018] The method of the present disclosure significantly shortens the annealing time without any loss in the mechanical properties (like strength) of the resultant polymeric material, and also, saves time. The method impedes yield of residual monomers and prevents occurrence of any backbiting reaction.
[0019] The first monomer includes L-lactide. The second monomer is Glycolide. The ratio by mole between the first monomer (L-lactide) and the second monomer (Glycolide) is 10:90. Via the ring opening polymerizing technique, the ring structures of each of L-lactice and Glycolide are converted to linear structures of lactic acid (LA) and glycolic acid (GA).
[0020] The initiator is at least one of diethylene glycol (DEG), lauryl alcohol, etc. The pre-defined amount of the initiator used to prepare the resorbable polymer, ranges from 10 ppm to 100000 ppm. In an exemplary embodiment, the initiator is DEG. DEG acts a bifunctional initiator which initiates the ring opening polymerization of the monomers. Being a bi-functional initiator, DEG can act to form both linear and crosslinked chains resulting in a polymeric material that has superior properties compared to conventionally prepared polymers.
[0021] The catalyst is at least one of stannous chloride (SnCl2), stannous octoate, etc. dissolved in at least one organic solvent. The organic solvent is at least one of toluene, benzene, etc. In an exemplary embodiment, the catalyst is 0.3M SnCl2 dissolved in toluene.
[0022] Now referring to the figures, Fig. 1 depicts an exemplary method 100 for preparation of a resorbable polymer. The method 100 is executed with the help of an apparatus 200 (as shown in Figs. 2 and 2a), for example, 4CV DIT Helicone Mixer (procured from Federal Equipment Company). However, the method 100 may be executed with the help of other functionally similar apparatus to produce the resorbable polymer and the same is within the scope of the teachings of the present disclosure.
[0023] The apparatus 200 includes at least a vessel 201 (optionally having a lid 203) with an oil jacket 205 (as shown in Fig. 2a) for controlling temperature of the vessel 201. The vessel 201 is provided with at least one vacuum port (coupled to a vacuum pump or the like) to create vacuum inside the vessel 201, at least one purge port to purge the vessel 201 with a pre-defined gas or the like, at least one vent port to release the pressure/gas from within the vessel 201, at least one stirrer 207 (having a plurality of blades 207a as shown in Fig. 2a) for stirring the contents of the vessel 201, a charging port to introduce material inside the vessel 201, and a discharge port to release the contents of the vessel 201. Each of the ports of the apparatus 200 is provided with a valve to enable voluntarily opening and closing of the respective port independent of the other. Optionally, the vessel 201 is provided with a transparent window to allow the inside of the vessel 201 and the contents thereof, to be observed from outside the vessel 201.
[0024] Before commencing the method 100, additionally or optionally, the portions/surfaces of the apparatus 200 that might be in touch with a reaction mixture, are cleaned and are neutralized to pH 7 using de-mineralized water. A litmus solution or strip may be used to check the pH of the surface of the apparatus 200 as acidity or alkalinity of the surfaces of the apparatus 200 may adulterate the reaction mixture.
[0025] Before commencing the method 100, an oil (for example, a food grade oil) is circulated in the oil jacket 205 of the vessel 201 at 40 psi or more. The oil jacket 205 may include at least one inlet port 205a and at least one outlet port 205b for the oil to circulate through the oil jacket 205. A pump or the like is used to circulate the oil across the inlet port 205a and the outlet port 205b of the oil jacket 205. The oil pressure is monitored to ensure it is not dropped to confirm that oil is not leaking out of the oil jacket 205. If the oil leaks, the oil might seep into the vessel 201 and may adulterate the reaction mixture.
[0026] Before commencing the method 100, the lid 203 is bolted to the vessel 201 with an O-ring placed in between to prevent any leakage. All the valves of the ports provided with the vessel 201 are closed. A heating line is connected to the inlet port 205a and the outlet port 205b of the oil jacket 205 without any leaks. The heating line allows a user to adjust the temperature of the circulating oil (i.e., oil temperature) thereby allowing the user to adjust the temperature within the vessel 201 (i.e., vessel temperature). In an exemplary embodiment, the heating line is set at 225 °C.
[0027] The method commences at step 101 by creating a vacuum inside the vessel 201 for a pre-defined time period once the vessel temperature is more than a pre-defined temperature. The pre-defined time period ranges from 15 min to 45 min. The pre-defined temperature ranges from 200 °C to 245 °C. In an exemplary embodiment, the vacuum is maintained inside the vessel 201 for 15 min once the vessel temperature reaches 200 °C. The vacuum maintained inside the vessel 201 helps to remove the moisture from within the vessel 201.
[0028] Additionally or optionally, after removing the moisture from within the vessel 201, the valve of the vacuum port is closed. The pressure inside the vessel 201 is monitored to ensure it is not dropped for at least 1hr to confirm that the vessel 201 is not leaking. Any leaks in the vessel 201 may be detrimental to the contents of the vessel 201 or any individual nearby the vessel 201, during the subsequent steps of the method 100.
[0029] At step 103, the vessel 201 is purged with a pre-defined inert gas for one or more cycles. The inert gas includes, without limitation, nitrogen, argon, etc. In an exemplary embodiment, the vessel 201 is purged with 99% nitrogen for two cycles. Each cycle of purging the vessel includes increasing a vessel pressure to a first pre-defined pressure and then decreasing the vessel pressure to a second pre-defined pressure. The first pre-defined pressure ranges from 0.5 psi to 40 psi. The second pre-defined pressure ranges from 0.5 psi to 40 psi. Purging the inert gas within the vessel 201 helps to equilibrate the inert environment within the vessel 201.
[0030] In an exemplary embodiment, the vessel 201 is purged with nitrogen up to 20 psi by opening the valve of the purge port. Thereafter, the valve of the purge port is closed and the valve of the vent port is opened till the pressure of nitrogen in the vessel 201 drops to 1 psi.
[0031] At step 103a, a pre-defined flow rate of the pre-defined inert gas is established across the vessel 201. The pre-defined flowrate of the inert gas ranges from 2 CFH to 17 CFH. The pre-defined flow rate of the inert gas is attained by opening the valve of the purge port as well as the valve of the vent port, thereby circulating the inert gas across the vessel 201. In an exemplary embodiment, the vessel 201 has a flow rate of the nitrogen is maintained at 15 CFH. The circulation of the inert gas provides and maintains an inert environment within the vessel 201 for the subsequent steps of the method 100. Until stated otherwise, the circulation of the inert gas across the vessel 201 is maintained throughout the subsequent steps of the method 100.
[0032] At step 105, a predefined amount of the first monomer and a pre-defined amount of the second monomer are added to the vessel 201 in a pre-defined ratio by weight. The first monomer and the second monomer are added to the vessel 201 by momentarily opening the valve of the charging port. The first monomer is L-lactide. The second monomer is Glycolide. The quantity of the second monomer being added in the vessel 201 is more than the quantity of the first monomer being added in the vessel 201. In an exemplary embodiment, 230 g of L-lactide (first monomer) and 1400 g of Glycolide (second monomer) are added to the vessel 201 in a ratio by weight of about 1:6.
[0033] In an exemplary embodiment, the blades 207a of the stirrer 207 are positioned away from the charging port of the vessel 201 such that the contents added to the vessel 201 reach the bottom of the vessel 201 with minimal sticking to the blades 207a of the stirrer 207. Ensuring that the minimal amount of material is stuck to the blades 207a of the stirrer 207, ensures that the contents of the vessel 201 do not climb up the blades 207a of the stirrer 207 during the subsequent steps of method 100.
[0034] The vessel temperature may reduce after the first monomer and the second monomer are added to the vessel 201. In an exemplary embodiment, the vessel temperature reduces to about 177 °C from 189 °C.
[0035] At step 105a, the first monomer and the second monomer are stirred at a pre-defined speed to homogenously mix the contents of the vessel 201. The pre-defined speed of the stirrer 207 ranges from 1 rpm to 50 rpm. In an exemplary embodiment, the contents of the vessel 201 are stirred at 50 rpm. While the contents of the vessel 201 are stirred, the vessel temperature continues to rise gradually.
[0036] At step 107, a predefined amount of the initiator is added to the vessel 201 when the vessel temperature reaches a pre-defined temperature. The pre-defined temperature is at 190 °C or more. The initiator is added by momentarily opening the charging port of the vessel 201. The initiator is at least one of diethylene glycol (DEG), lauryl alcohol, etc. In an exemplary embodiment, 0.96 g of DEG is added to the vessel 201 when the vessel temperature is 190 °C. The initiator helps to promote the ring opening polymerization of the monomers and acts as a bifunctional initiator.
[0037] In an exemplary embodiment, before adding the initiator, the blades 207a of the stirrer 207 are stopped and positioned away from the charging port of the vessel 201 such that the contents added to the vessel 201, reach the bottom of the vessel 201 with minimal sticking to the blades 207a of the stirrer 207. Ensuring that the minimal amount of material is stuck to the blades 207a of the stirrer 207 ensures that the contents of the vessel 201 do not climb up the blades 207a of the stirrer 207 during the subsequent steps of method 100.
[0038] The vessel temperature may reduce after the initiator is added to the vessel 201. In an exemplary embodiment, the vessel temperature reduces to about 171 °C from 180 °C.
[0039] At step 107a, the first monomer, the second monomer and the initiator are stirred at a pre-defined speed to homogenously mix the contents of the vessel 201. The pre-defined speed of the stirrer 207 ranges from 1 rpm to 50 rpm. In an exemplary embodiment, the contents of the vessel 201 are stirred at 50 rpm. While the contents of the vessel 201 are stirred, the vessel temperature continues to rise gradually.
[0040] At step 109, a predefined amount of the catalyst is added to the vessel 201 when the vessel temperature reaches a pre-defined temperature. The pre-defined temperature is at 190 °C or more. The catalyst is added by momentarily opening the charging port of the vessel 201. The catalyst is at least one of stannous chloride (SnCl2), stannous octoate, etc. dissolved in at least one organic solvent. The organic solvent is at least one of toluene, benzene, etc. In an exemplary embodiment, 0.187 g of SnCl2 dissolved in toluene (at 0.3M) is added to the vessel 201 when the vessel temperature is 190 °C. The catalyst helps to catalyze the reaction.
[0041] In an exemplary embodiment, before adding the catalyst, the blades 207a of the stirrer 207 are stopped and positioned away from the charging port of the vessel 201 such that the contents added to the vessel 201 reach the bottom of the vessel 201 with minimal sticking to the blades 207a of the stirrer 207. Ensuring that the minimal amount of material is stuck to the blades 207a of the stirrer 207 ensures that the contents of the vessel 201 do not climb up the blades 207a of the stirrer 207 during the subsequent steps of method 100.
[0042] The vessel temperature may reduce after the catalyst is added to the vessel 201. In an exemplary embodiment, the vessel temperature reduces to about 181 °C from 188 °C.
[0043] The catalyst is added at the last because it helps to push down the initiator if any of it is stuck to the blades 207a of the stirrer 207.
[0044] After step 109a, hereon after, the contents of the vessel 201 are collectively termed as a reaction mixture.
[0045] At step 109a, the reaction mixture is stirred at a pre-defined speed to homogenously mix the contents of the vessel 201. The pre-defined speed of the stirrer 207 ranges from 33 rpm to 37 rpm. In an exemplary embodiment, the contents of the vessel 201 are stirred at 35 rpm. While the contents of the vessel 201 are stirred, the vessel temperature continues to rise gradually.
[0046] At step 111, the vessel 201 is again purged with a pre-defined inert gas for one or more cycles as described in step 103. Each cycle of purging the vessel 201 includes increasing a vessel pressure to a first pre-defined pressure and then decreasing the vessel pressure to a second pre-defined pressure. The first pre-defined pressure ranges from 0.5 psi to 40 psi. The second pre-defined pressure ranges from 0.5 psi to 40 psi.
[0047] In an exemplary embodiment, the vessel 201 is purged with nitrogen for five cycles. For each cycle, the vessel 201 is purged with nitrogen up to 30 psi by opening the valve of the purge port. Thereafter, the valve of the purge port is closed and the valve of the vent port is opened till the pressure of nitrogen in the vessel drops to 20 psi.
[0048] At step 111a, a pre-defined flow rate of the pre-defined inert gas is established across the vessel 201 as described in step 103a. The pre-defined flowrate of the inert gas ranges from 2 CFH to 20 CFH. In an exemplary embodiment, the flow rate of the nitrogen is maintained at 15 CFH.
[0049] At step 113, the reaction mixture is subjected to heating for at least three stages, namely, a first stage, a second stage, and a third stage. The heating is controlled by adjusting the oil temperature of the oil jacket 205 thereby, adjusting the vessel temperature. Accordingly, each stage of heating includes a respective oil temperature and a respective vessel temperature.
[0050] The oil temperature in the first stage of heating, ranges from 140 °C to 242 °C. The vessel temperature in the first stage of heating, ranges from 140 °C to 242 °C. The oil temperature in the second stage of heating, ranges from 200 °C to 250 °C. The vessel temperature in the second stage of heating, ranges from 200 °C to 250 °C. The oil temperature in the third stage of heating, ranges from 210 °C to 260 °C. The vessel temperature in the third stage of heating, ranges from 210 °C to 260 °C.
[0051] The reaction mixture is heated at the first stage until the vessel temperature of the first stage is reached. The reaction mixture is heated at the second stage for a pre-defined time ranging from 2 hr to 3 hr. The reaction mixture is heated at the third stage for a pre-defined time ranging from 3 hr to 7 hr.
[0052] In an exemplary embodiment, the reaction mixture is heated in three stages as shown in Table 1. The vessel temperature described in Table 1 corresponds to the maximum vessel temperature at the set oil temperature.
Stage Oil Temperature Vessel Temperature Time
First stage 266 °C 240 °C Till vessel temperature reaches 240 °C.
Second stage 282 °C 240 °C 2hr
Third stage 298 °C 255 °C 5hr
(Table 1)
[0053] In an alternate embodiment, if a portion of the reaction mixture is stuck to the blades 207a of the stirrer 207 after heating the reaction mixture for 2hr, the total time of heating the reaction mixture at the third stage is increased by 1hr. Increasing the total time of the third stage ensures that the reaction mixture stuck to the blades 207a of the stirrer 207 melts and falls off the blades 207a of the stirrer 207.
[0054] During the at least three stages of heating, the first monomer (L-lactide having formula I) and the second monomer (Glycolide having formula II) are polymerized to produce the resorbable polymer (Poly(lactic-co-glycolic acid) having formula III) as depicted by the following illustration:

(Formula I) (Formula II) (Formula III)
[0055] At step 115, the flow of the pre-defined inert gas is stopped across the vessel 201. The flow of the inert gas is stopped by closing the valve of the vent port and the purge port.
[0056] At step 117, the vessel 201 is swept for one or more cycles to remove any unreacted second monomer. The steps of one cycle are described in step 117a, 117b, and 117c.
[0057] At step 117a, a vacuum is gradually created within the vessel 201 for a pre-defined amount of time. The pre-defined amount of time ranges from 1 min to 120 mins. In an exemplary embodiment, the vacuum is created by slowly opening the valve of the vacuum port for 5 mins. It is important to open the valve of the vacuum port slowly, else, the solid contents of the vessel 201 may be pulled through the vacuum port and choke the ports of the apparatus 200 leading to failure of the method 100.
[0058] At step 117b, the vacuum is held within the vessel 201 for a pre-defined amount of time. The pre-defined amount of time ranges from 10 min to 120 min. The vacuum is held by closing the valve of the vacuum port for 10 min.
[0059] At step 117c, the vessel 201 is purged with the pre-defined inert gas for a pre-defined amount of time. The vessel 201 is purged by opening the valve of the purge port for the pre-defined amount of time and allowing the pre-defined inert gas to fill the vessel 201. The pre-defined time ranges from 1 min to 20 mins. In an exemplary embodiment, the vessel 201 is purged with nitrogen by opening the valve of the purge port for 5 mins. The pressure in the vessel 201 may rise up to 0-0.5 psi, and the flow rate of the inert gas may be set at 1 L/min to 10 L/min. In an exemplary embodiment, the pressure in the vessel 201 rises to 0.3 psi and the flow rate of the inert gas is set at 5 L/min.
[0060] In an exemplary embodiment, the sweeping cycle described in the above steps 117a, 117b, and 117c are repeated for three more times. Sweeping the vessel 201 helps in removal of any unreacted Glycolide (i.e., the second monomer) from the reaction mixture and the vessel 201.
[0061] Alternatively, instead of the steps 117a, 117b, and 117c, the vessel 201 is swept by simultaneously creating a vacuum and purging the pre-defined inert gas for a pre-defined time. The pre-defined time ranges from 1 min to 120 mins. The vacuum is created by slowly opening the valve of the vacuum port while simultaneously opening the valve of the purge port for the pre-defined amount of time. In an exemplary embodiment, the vacuum is created in the vessel 201 while it is purged with nitrogen for 120 minutes.
[0062] At step 119, a cooling tunnel (procured from Ami Cooling Pvt. Ltd) provided with a conveyor belt, is positioned beneath the discharge port of the vessel 201.
[0063] An exemplary cooling tunnel 300 with a conveyor belt 301 is depicted in Fig. 3. The cooling tunnel 300 has a pre-defined shaped defining a lumen. In the depicted embodiment, the cooling tunnel 300 has a cuboidal shape having a length of 500 cm, a width of 50 cm, and a height of 68.8 cm. The conveyor belt 301 is at least partially disposed within the lumen of the cooling tunnel 300. In the depicted embodiment, the conveyor belt 301 has a length of 543.1 cm and a width of 26 cm. The conveyor belt 301 is operationally coupled to a motor (not shown) or the like to allow the conveyor belt 301 to transport materials across the length of the cooling tunnel 300.
[0064] The cooling tunnel 300 is set at a pre-defined temperature for a pre-defined time period. The pre-defined temperature ranges from 0 °C to 30 °C. The pre-defined time period ranges from 5 min to 120 min. In an exemplary embodiment, the cooling tunnel 300 is set at 1 °C for 10 mins. Setting the pre-defined temperature for the pre-defined time period ensures proper cooling of the conveyor belt 301.
[0065] At step 119a, the resorbable polymer is released from the discharge port of the vessel 201 to the conveyor belt 301. The conveyor belt 301 helps to move the resorbable polymer across the cooling tunnel 300 and cool the resorbable polymer.
[0066] Additionally, or optionally, the resorbable polymer obtained from the step 117a is pelletized using a pelletizer (procured from Ami Cooling pvt. Ltd) and stored in clean and dry containers. Pelletizing the resorbable polymer to pellets helps to further process the pellets in a downstream operation and to extrude the pellets as and when required.
[0067] At step 121, the pellets of the resorbable polymer or the resorbable polymer obtained from step 119a are annealed using a Rotocone vacuum dryer (RCVD, procured from Industrial Fabricators Pvt. Ltd.) for a pre-defined amount of time. The pre-defined amount of time ranges from 2 hours to 24 hours for 0.5 kg to 45 kg of the resorbable polymer. In an exemplary embodiment, 22 kg of the pellets of the resorbable polymer are dried in the RCVD for 12 hours under full vacuum. Annealing the resorbable polymer helps to completely remove any unreacted Glycolide (i.e., the second monomer). The unreacted Glycolide, if not removed from the resorbable polymer will affect the degradation properties and strength of the resorbable polymer over time.
[0068] The resorbable polymer obtained from the method 100 does not include any unreacted Glycolide (i.e., the second monomer). The resorbable polymer can be stored for long period of time without any degradation and loss in strength.
[0069] The present disclosure will now be explained using the following examples.
[0070] Example 1: Method to prepare the resorbable polymer of the present disclosure
[0071] A vacuum was created and maintained inside the vessel 201 for 15 min once the vessel temperature reached 200 °C. The vessel 201 was purged with nitrogen up to 20 psi by opening the valve of the purge port. Thereafter, the valve of the purge port was closed and the valve of the vent port was opened till the pressure of nitrogen in the vessel 201 dropped to 1 psi. The flow rate of the nitrogen was maintained across the vessel 201 at 15 CFH. 230 g of L-lactide (first monomer) and 1400 g of Glycolide (second monomer) were added to the vessel 201 and were stirred at 50 rpm. 0.96 g of DEG was added to the vessel 201 when the vessel temperature reached 190 °C and were stirred at 50 rpm. 0.187 g of SnCl2 dissolved in toluene (at 0.3M) was added to the vessel 201 when the vessel temperature reached 190 °C and were stirred at 35 rpm. The vessel 201 was purged with nitrogen for five cycles. For each cycle, the vessel 201 was purged with nitrogen up to 30 psi by opening the valve of the purge port. Thereafter, the valve of the purge port was closed and the valve of the vent port was opened till the pressure of nitrogen in the vessel drops to 20 psi. The flow rate of the nitrogen was maintained across the vessel 201 at 15 CFH.
[0072] Thereafter, the monomers were polymerized by setting the oil temperature at 266 °C until the vessel temperature reached 240 °C. Then the oil temperature was set at 282 °C for 2 hours. Then, the oil temperature was set at 298 °C for 5 hours. Thereafter, the flow of the inert gas was stopped by closing the valve of the vent port and the purge port.
[0073] Thereafter, the vessel 201 was swept for four cycles. In each cycle, a vacuum was created by slowly opening the valve of the vacuum port for 5 min. The vacuum was held by closing the valve of the vacuum port for 10 min. The vessel 201 was purged with nitrogen by opening the valve of the purge port for 5 min.
[0074] Thereafter, the cooling tunnel 300 was set at 1 °C for 10 mins. The resorbable polymer was released from the discharge port of the vessel 201 to the conveyor belt 301 of the cooling tunnel 300. After cooling the resorbable polymer, the resorbable polymer was pelletized using a pelletizer. The pellets of the resorbable polymer were annealed in the RCVD for 12 hours under full vacuum to remove all the unreacted Glycolide.
[0075] Example 2: Conventional method to prepare a resorbable polymer
[0076] A vacuum was created and maintained inside the vessel 201 for 15 min once the vessel temperature reached 200 °C. The vessel 201 was purged with nitrogen up to 20 psi by opening the valve of the purge port. Thereafter, the valve of the purge port was closed and the valve of the vent port was opened till the pressure of nitrogen in the vessel 201 dropped to 1 psi. The flow rate of the nitrogen was maintained across the vessel 201 at 15 CFH. 230 g of L-lactide (first monomer) and 1400 g of Glycolide (second monomer) were added to the vessel 201 and were stirred at 50 rpm. 0.96 g of DEG was added to the vessel 201 when the vessel temperature reached 190 °C and were stirred at 50 rpm. 0.187 g of SnCl2 dissolved in toluene (at 0.3M) was added to the vessel 201 when the vessel temperature reached 190 °C and were stirred at 35 rpm. The vessel 201 was purged with nitrogen for five cycles. For each cycle, the vessel 201 was purged with nitrogen up to 30 psi by opening the valve of the purge port. Thereafter, the valve of the purge port was closed and the valve of the vent port was opened till the pressure of nitrogen in the vessel drops to 20 psi. The flow rate of the nitrogen was maintained across the vessel 201 at 15 CFH.
[0077] Thereafter, the monomers were polymerized by setting the oil temperature at 266 °C until the vessel temperature reached 240 °C. Then the oil temperature was set at 282 °C for 2 hours. Then, the oil temperature was set at 298 °C for 5 hours. Thereafter, the flow of the inert gas was stopped by closing the valve of the vent port and the purge port.
[0078] Thereafter, the cooling tunnel 300 was set at 1 °C for 10 mins. The resorbable polymer was released from the discharge port of the vessel 201 to the conveyor belt 301 of the cooling tunnel 300. After cooling the resorbable polymer, the resorbable polymer was pelletized using a pelletizer. The pellets of the resorbable polymer were annealed in the RCVD for more than 4 days under full vacuum to remove all the unreacted Glycolide.
[0079] Example 3: Characterization of the resorbable polymer of the present disclosure
[0080] The resorbable polymer obtained from example 1 above was off-white to light brown in color. The resorbable polymer had an inherent viscosity of 1.5 dL/g to 1.8 dL/g as measured using Ubblehode Viscometer (procured from Bombay Glass Company). The ratio of Glycolide to L-lactide in the resorbable polymer was 90:10 by mole with less than 20 ppm of Tin (Sn) as measured using atomic absorption spectroscopy (AAS, procured from Shimadzu).
[0081] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. , C , C , Claims:WE CLAIM:
1. A method (100) to prepare resorbable polymer, the method (100) comprising:
a. adding a predefined amount of a first monomer, a pre-defined amount of a second monomer, a pre-defined amount of an imitator, and a pre-defined amount of catalyst in a vessel (201) to obtain a reaction mixture, the quantity of the second monomer being more than the quantity of the first monomer, the vessel (201) having circulation of a pre-defined inert gas;
b. subjecting the reaction mixture to heating thereby, polymerizing the first monomer and the second monomer to obtain the resorbable polymer;
c. sweeping the vessel (201) for one or more cycles to remove any unreacted second monomer, each cycle includes:
i. creating a vacuum inside the vessel (201) for a pre-defined amount of time,
ii. holding the vacuum inside the vessel (201) for a pre-defined amount of time,
iii. purging the inert gas inside the vessel (201) for a pre-defined amount of time;
d. cooling the resorbable polymer;
e. annealing the resorbable polymer for a pre-defined amount of time to remove any unreacted second monomer, the pre-defined amount of time ranging from 2 hours to 24 hours.
2. The method (100) as claimed in claim 1, wherein the step of adding the predefined amount of the first monomer and the pre-defined amount of the second monomer includes adding L-lactide and Glycolide in the vessel (201) in a ratio by weight of about 1:6.
3. The method (100) as claimed in claim 1, wherein the step of adding the predefined amount of the initiator includes adding at least one of diethylene glycol (DEG), and lauryl alcohol in the vessel (201).
4. The method (100) as claimed in claim 1, wherein the step of adding the predefined amount of the catalyst includes adding at least one of stannous chloride (SnCl2), and stannous octoate in the vessel (201).
5. The method (100) as claimed in claim 1, wherein the step of subjecting the reaction mixture to heating includes:
a. a first stage of heating the vessel (201) for increasing a vessel temperature in a range of 140 °C to 242 °C;
b. a second stage of heating the vessel (201) for increasing the vessel temperature in a range of 200 °C to 250 °C; and
c. a third stage of heating the vessel (201) for increasing the vessel temperature in a range of 210 °C to 260 °C.
6. The method (100) as claimed in claim 1, wherein the step of creating the vacuum inside the vessel (201) includes creating the vacuum for 1 min to 120 min.
7. The method (100) as claimed in claim 1, wherein the step of holding the vacuum inside the vessel (201) includes holding the vacuum for 10 min to 120 min.
8. The method (100) as claimed in claim 1, wherein the step of purging the inert gas inside the vessel (201) includes purging nitrogen for 1 min to 20 min.
9. The method (100) as claimed in claim 1, wherein the step of annealing the resorbable polymer includes annealing the resorbable polymer using a Rotocone vacuum dryer.
10. A resorbable polymer obtained from the method (100) as claimed in any of the preceding claims.