Title of Invention

"A PROCESS FOR PREPARATION OF POLYGLOCOLIC ACID SUITABLE FOR SURGICAL SUTURES"

Abstract This invention relates to a process for preparation of polyglycolic acid suitable for surgical suture comprising six-stage polymerisation of dried commercial glycolide by heating in a container kept in an oil bath, subjecting the molten viscous mass thus obtained to vacuum evaporation at vacuum of 5-50 mm Hg for 10-30 min, cooling to room temperature under nitrogen atmosphere, converting the polymer thus obtained into chips, subjecting the chips thus prepared to solid state post polymerization under vacuum in the range of 0.001 to 0.05mn Hg at temperature of 140°C-220°C for 4-48 hours wherein container is provided with stirrer, condenser, thermometer and an inlet for nitrogen and wherein the first stage polymerization comprises heating glycolide at 25-60°C for 5-25 min and adding stannous chloride dihydrate (SnCl2. 2H20) as catalyst in the range of 0.001-0.005% of glycolide, second stage polymerisation comprises increasing the temperature to 100-150°C for 10-40 min and adding lauryl alcohol as initiator, in the concentration range of 0.85 to 3 ml/kg and the third stage polymerization comprises heating at 150-175°C for 35-75 min, the fourth stage polymerisation comprises heating at 170-190°C for 10-25 min, the fifth stage polymerisation comprises heating at 190-220°C for 10-25 min and the sixth stage comprises heating at 220-250°C for 20-55 min under nitrogen atmosphere.
Full Text FIELD OF INVENTION
This invention relates to a process for preparation of polyglycolic acid (PGA) which has applications in wound closure devices such as surgical sutures.
PRIOR ART
Polyglycolic acid is the simplest linear aliphatic polyester of glycolic acid. It is biocompatible and slowly degrades into non-toxic moieties. It has application in medicine and pharmaceutical fields such as; resorbable bone fixation devices, surgical sutures and controlled drug release devices.
One of the process known in the art for preparation of polyglycolic acid for medical use as per U.S.Patent no. 6150497 comprises use of a conical vortex reactor wherein stannous chloride dihydrate is used as catalyst in the concentration range of 0.0005-0.028 g/kg of glycolide and lauryl alcohol is used as initiator in the concentration of 0.0-0.8 ml/kg of glycolide, raising polymerisation temperature in steps, between the range of 120-220°C. The PGA obtained has inherent viscosity of 1.10 dl/g in hexafluoroacetone resquihydrate at 30°C.
A limitation of the above process is that the process does not lead to the desired quality of polymer.

Another disadvantage of the process is that in the above process, the residual monomer content is not eliminated which is necessary for satisfactory extrusion into end product.
According to another process known in the art as per U.S. Patent no. 3442871, comprises use of a heavy walled sealed glass tube, evacuated to less than 1 mm Hg and wherein SnCl2. 2H2O in concentration of 0.0005% to 0.0025% is used as catalyst and lauryl alcohol taken in 0.2 to 0.8 mol% of glycolide, is used as initiator. The polymerization was carried out at a temperature between 220 to 230° C for about 60 to 90 minutes varying inversely.
A disadvantage of the above process is that the above process cannot be used as such for industrial production. Further disadvantage is that the glycolide used in the process requires to be isomerically purified before polymerization.
According to still another process known in the art as per Japanese patent no. 58,013,624, stannous octanate is used in the concentration range of 0.01 to 0.05 wt% of glycolide and 10-15 carbon straight chain aliphatic alcohol preferably lauryl alcohol 0.5-2.8 times weight of octanate is used.
A disadvantage of the above process is that it uses tin octanate as a catalyst, which has recently been suspected for some toxicity level.
According to yet another process known in the art for preparation of polyglycolic acid (PGA), a combination of stannous octanate and stannous chloride in concentration range of 0.0003-0.0008 wt% of glycolide is used.
Besides toxicity of stannous octanate, the glycolide used in the process of polymerization is highly pure isomer, which adds to the additional cost of manufacturing.
According to a yet another process known in the art as per U.S. Patent no. 3,890,283, PGA molecule is subjected to elevated temperature and vacuum of 0.1 mm Hg, preferably at temperature of 150-220°C for a period of atleast four days to produce ultra high molecular weight PGA. The said art requires longer duration to achieve desired molecular weight polymer.
According to even another process known in the art as per US 3565869 for preparation of extrudable and stretchable PGA, the molecule of PGA polymer is devolatilised with a flowing stream of Argon gas having temperature of 20-190°C, gas flow rate of 0.35 to
l0scfh/lb of polymer (standard cubic feet per hour/pound) and a pressure of 0.01 mm Hg to 10 psig and time of 4-180 hours.
The process has the disadvantage of using plenty of inert gas for carrying out the process. OBJECTS OF PRESENT INVENTION
An object of (he present invention is to propose a process for preparation of PGA suitable for spinning into fiber for use as surgical suture.
STATEMENT OF INVENTION
According to this invention there is provided a process for preparation of polyglycolic acid for surgical suture comprising six-stage polymerisation of dried commercial glycolide by heating in a container kept in an oil bath, subjecting the molten viscous mass thus obtained to vacuum evaporation at vacuum of 5-50 mm Hg for 10-30 min, cooling to room temperature under nitrogen atmosphere, converting the polymer thus obtained into chips, subjecting the chips thus prepared to solid state post polymerization under vacuum in the range of 0.001 to 0.05mn Hg at temperature of 140°C-220°C for 4-48 hours wherein container is provided with stirrer, condenser, thermometer and an inlet for
nitrogen and wherein the first stage polymerization comprises heating glycolide at 25-60°C for 5-25 min and adding stannous chloride dihydrate (SnCl2. 2H2O) as catalyst in the range of 0.0001-0.005% of glycolide, second stage polymerisation comprises increasing the temperature to 100-150°C for 10-40 min and adding lauryl alcohol as initiator, in the concentration range of 0.85 to 3ml/kg and the third stage polymerisation comprises heating at 150-175°C for 35-75 min, the fourth stage polymerisation comprises heating at 170-190°C for 10-25 min, the fifth stage polymerisation comprises heating at 190-220°C far 10-25 min and the sixth stage comprises heating at 220-250°C for 20-55 min under nitrogen atmosphere.
DESCRIPTION OF INVENTION
In the present invention, the commercial glycolide is first dried before polymerizing into polyglycolide. The polymerization is carried out in an oil bath using four neck round bottom flask equipped with stirrer, thermometer, gas inlet and a condenser. 25-500g of dried glycolide is transferred into the flask at 25°C - 60°C and is held for 5-25 minutes. Then catalyst SnCl2. 2H2O is added to it in the concentration range of 0.0001-0.005% of glycolide. Now, temperature is raised to 100-150°C and this temperature is maintained
for 10-40 minutes. On heating at above temperature, a clear liquid is obtained. To this clear liquid, initiator lauryl alcohol is added in the concentration range of 0.85-3.0 ml/kg of glycolide. The reaction mixture was stirred. The polymerisation starts on adding the initiator and is allowed to continue for 15-45 minutes at 110-150°C. On completion of this polymerization process, the temperature is raised to 150-175°C and maintained for 35-75 min. Then the temperature of the molten mass is raised to 170°C-190°C and kept for 10-25 minutes. After this period, the temperature is further increased to 190°C-220°C and kept at this temperature for 10-25 min. Finally, the temperature of the reaction mass is raised to 320-250°C and kept at this temperature for 20-55 minutes. The molten viscous mass is subjected to vacuum of 5-50 mm Hg for 10-30 min. The mass is cooled to room temperature under inert atmosphere. The polymer prepared using the above process, was converted into chips of size upto 5 mm, preferably 2-4 mm. These chips are subjected to solid state polymerization under vacuum in the range of 0.001 to 0.05mm Hg at temperature of 140-220°C for a period of 4 to 48 hours. The PGA thus obtained has inherent viscosity (ηinh) in the range of 0.50 to 0.8 dl/g in phenol trichlorophenol (6:4) at 30°C; Melting Temperature (Tm)=2l5 to 225°C and Melt Volume Index (MVI) in the range of 15-25 cc/10 min. (at 230°C and 1.2 kg load).
WORKING EXAMPLES
The invention will now be illustrated with a working example which is intended to illustrate working of invention and is not intended to be taken restrictively to imply any limitation on the scope of present invention.
EXAMPLE 1
50 g of dried glycolide was charged into a round bottom flask. The glycolide was kept at 60°C for 5 min. under N2 atmosphere. Solution of 0.00015 g of SnCl2. 2H2O in an organic solvent was added. Now the temperature of the reaction mixture was raised to 125°C and was held at this temperature. In the molten glycolide, 0.135 ml of lauryl alcohol was added. The reaction mixture was stirred for 40 minutes. The temperature was raised lo 170°C and held for 70 minutes.
The temperature was further raised to 185°C and held for 10 minutes. The temperature was raised to 240°C and held for 30 minutes and additionally 30 minutes under vacuum of 1 mm Hg. After completion of polymerization time, the molten mass was quenched. The polymer was further converted into chips and subjected to post polymerization at 200°C for 48 hour under vacuum of 0.0lmmHg. The prepared PGA had inherent viscosity of 0.60 dl/g; Melting Volume Index (MVI) 21 cc/10 min and Melting Temperature (Tm) of 225°C.
It is to be noted that the present invention is susceptible to modifications, changes and adaptations by those skilled in the art. Such variant embodiments incorporating the concepts and features of the present invention, are intended to be within the scope of the present invention, which is further set forth under the following claims:-







WE CLAIM:
1. A process for preparation of polyglycolic acid suitable for surgical suture comprising six-stage polymerisation of dried commercial glycolide by heating in a container kept in an oil bath, subjecting the molten viscous mass thus obtained to vacuum evaporation at vacuum of 5-50 mm Hg for 10-30 min, cooling to room temperature under nitrogen atmosphere, converting the polymer thus obtained into chips, subjecting the chips thus prepared to solid state post polymerization under vacuum in the range of 0.001 to 0.05mn Hg at temperature of 140°C-220°C for 4-48 hours wherein container is provided with stirrer, condenser, thermometer and an inlet for nitrogen and wherein the first stage polymerization comprises heating glycolide at 25-60°C for 5-25 min and adding stannous chloride dihydrate (SnCl2. 2H2O) as catalyst in the range of 0.001-0.005% of glycolide, second stage polymerisation comprises increasing the temperature to 100-150°C for 10-40 min and adding lauryl alcohol as initiator, in the concentration range of 0.85 to 3 ml/kg and the third stage polymerization comprises heating at 150-175°C for 35-75 min, the fourth stage polymerisation comprises heating at 170-190°C for 10-25 min, the fifth stage polymerisation comprises heating at 190-220°C for 10-25 min and the sixth stage comprises heating at 220-250°C for 20-55 min under nitrogen atmosphere.

2. A process as claimed in claim 1 wherein the size of said polymer chips is preferably 2-5 mm.
3. A process for preparation of polyglycolic acid suitable for surgical suture as substantially herein described and illustrated herein.

Documents:

1021-DEL-2003-Abstrac-(27-04-2009).pdf

1021-DEL-2003-Abstract-28-05-2008.pdf

1021-del-2003-abstract.pdf

1021-del-2003-assignment.pdf

1021-DEL-2003-Claims-(27-04-2009).pdf

1021-DEL-2003-Claims-28-05-2008.pdf

1021-del-2003-claims.pdf

1021-DEL-2003-Correspondence-Others-(27-04-2009).pdf

1021-del-2003-correspondence-others-28-05-2008.pdf

1021-del-2003-correspondence-others.pdf

1021-del-2003-correspondence-po.pdf

1021-DEL-2003-Description (Complete)-(27-04-2009).pdf

1021-del-2003-description (complete)-28-05-2008.pdf

1021-del-2003-description (complete).pdf

1021-DEL-2003-Form-1-28-05-2008.pdf

1021-del-2003-form-1.pdf

1021-del-2003-form-18.pdf

1021-DEL-2003-Form-2-(27-04-2009).pdf

1021-DEL-2003-Form-2-28-05-2008.pdf

1021-del-2003-form-2.pdf

1021-DEL-2003-Form-26-28-05-2008.pdf

1021-DEL-2003-Form-3-28-05-2008.pdf

1021-del-2003-form-6.pdf

1021-DEL-2003-GPA-(27-04-2009).pdf

1021-del-2003-gpa.pdf


Patent Number 249273
Indian Patent Application Number 1021/DEL/2003
PG Journal Number 42/2011
Publication Date 21-Oct-2011
Grant Date 14-Oct-2011
Date of Filing 19-Aug-2003
Name of Patentee STERICAT GUTSTRING PVT. LTD.
Applicant Address 19, UNIVERSITY ROAD, DELHI-110007, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 RAKESH KUMAR KAHNDAL SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCH, 19, UNIVERSITY ROAD, DELHI-110007, INDIA.
2 MOHAMMAD QAMAR PARWEZ SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCH, 19, UNIVERSITY ROAD, DELHI-110007, INDIA.
3 AJAY KUMAR SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCH, 19, UNIVERSITY ROAD, DELHI-110007, INDIA.
4 MOZAFFAR ALAM KHAN SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCH, 19, UNIVERSITY ROAD, DELHI-110007, INDIA.
5 SUMITA KAMATH SHRIRAM INSTITUTE FOR INDUSTRIAL RESEARCH, 19, UNIVERSITY ROAD, DELHI-110007, INDIA.
PCT International Classification Number C08J3/12
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA