|Title of Invention||
"PROCESS FOR PREPARATION OF CROSSLINKED PVA HYDROGELS"
|Abstract||A process for preparation of cross-linked PVA hydrogels is provided. The hydrogel was prepared by mixing an aqueous solution of a water soluble polymer with the cross-linking ion and optionally, adding an additive to the reaction mixture; reacting the components mixed at a temperature ranging from 50 to 100 degree C for a time period of 10 to 400 minutes; pouring the solution on an inert surface; drying it by evaporating the solvent and peeling - off the dried film and immersing it in water for about 20 minute to obtain the desired hydrogel. The said hydrogel was further tested for its water absorption, viscosity, thermal and mechanical characterization. These hydrogels have found to possess excellent water absorption capacity and hence, are useful in the wound healing applications. These hydrogels also act as ion exchange materials and can be used to remove heavy toxic metals from contaminated water.|
|Full Text||FIELD OF THE INVENTION
The present invention relates to a process for preparation of cross-linked PVA hydrogels. More
particularly, the present invention relates to a process for forming Polyvinyl alcohol (PVA) hydrogel
film useful in wound healing applications.
A major application of insoluble PVA films/hydrogels is in the field of wound healing. Cross-linked
PVA films have excellent water absorption capacity and they provide wet conditions around the wound
area, which heal much faster. These cross-linked PVA membranes do not dissolve in water and act as a
sterile dressing material for the wound. As the hydrogels are transparent, they allow observation of
wound healing process. This material is particularly important for burn wounds as these hydrogels
provide a cooling sensation. These absorb the exudates, which ooze out from the wounds, thereby
accelerating the healing phenomenon.
Cross-linked PVA films also find application as hydrophilic membranes for pervaporation. The
membranes prepared from cross-linked PVA can be used for breaking of ethanol-water and other
similar azeotropic mixtures as these selectively allow water molecules to pass over ethanol/methanol
These films also act as Ion Exchange Materials and can be used to remove heavy toxic metals from
Water insoluble PVA fibers can also be used as tire cords, and this kind of cord has the biggest market
among the industrial fibers.
Insoluble PVA based gels can also be used as a packing material in gel chromatography.
BACKGROUND AND PRIOR ART
Polyvinyl alcohol (PVA) is a polymer prepared from polyvinyl acetate by saponification (trans-esterification) process. However, the polymer may contain acetyl groups, which can substantially affect the properties and application of the polymer. A distinction is therefore made between fully and partially saponified grades.
Some applications for unmodified PVOH include warp sizing in textiles, fabric finishing, adhesives, paper processing additives, anil emulsifiers/dispersants. A major disadvantage of this polymer is that it
always dissolves in the long run, i.e. this polymer is not suitable for applications requiring a certain degree of insolubility. Insoluble PVA films are particularly important in the areas discussed above. Various methods for producing cross-linked PVA films have been proposed so far: Korean patent registration no. 210727 discloses a method for producing a polyvinyl alcohol fiber with excellent hot water resistance, in which acetal of aliphatic dialdehyde has been used as a cross-linking agent.
US patent number 3,249,572 and DE 694 03067 describe the preparation of cross-linked PVA by reaction with cross-linking agent like poly-ethyleneimine and mono-carboxylic acids respectively. US patent number 20050129656 describes the formation of a PVA hydrogel where the cross-linking is caused by the reaction of the cross-linkable groups attached to the pendant OH groups of PVA. US patent number 4619793 deals with the development of contact lens based on cross-linked PVA using cross-linking agents like formaldehyde, aliphatic or aromatic dialdehydes such as glutaraldehyde, terephthalaldehyde, aliphatic or aromatic reactive methylolated polyamines and methylolated polyamides, such as dimethylourea, dimethyloethylene urea, and trimethylolmelamine; glyoxal; oxalic acid; polyacrolein; divinyl compounds such as divinyl sulfone and compounds containnig vinyl sulfone precursors as end groups, such as .beta.-sulfatoethylsulfonyl and beta.-hydroxyethylsulfonyl, as well as reactive derivatives thereof; triazine derivatives such as 2,4,6-trichloro-l,3,5-triazine and compounds containing chrorinated triazine end groups, as well as reactive derivatives thereof; polyhydroxylated phenolic compounds such as dihydroxy diphenyl sulfone, dihydroxybenzenes such as resorcinol, and pyrogallol; aliphatic and aromatic polyepoxides such as 1,2,3,4-diepoxybutane and 1,2,7,8-diepoxy octane; aliphatic and aromatic diisocyanates such as ethylene diisocyanate, 1,2-diisocyanatopropane, 1,3- diisocyanatopropane, 2, 4- and 2, 6- toluene diisocyanate and hexamethylene diisocyanate; tetravalent borates, including alkali metal and alkaline earth metal borates, ammonium borates and amine borates, such as ammonium borate, calcium borate, sodium metaborate and sodium tetraborate and methyl ammonium hydrogen tetraborate; aqueous solutions of boric acid when the pH is adjusted to greater than 7; and tetravalent metal salts, including tetravalent metal salts of zirconium, vanadium, titanium and chromium, such as titanium sulfate, zirconium chloride, vanadyl sulfate, chromic nitrate and organic titanates. Thus, any conventional substantially non-opacifying chemical cross-linked agent for polyvinyl alcohol, capable of forming covalent bonds between itself and the polyvinyl alcohol in a suitable swelling solvent may be used.The use of poly (methyl vinyl ether/maleic anhydride) and/or polyacrylic acid as a cross-linking agent has been reported in US patent number
5,972,375. Similarly PVA in the presence of carboxylic, sulfate, hydroxy and amine functionalized groups may be ionically cross-linked using ions of calcium, magnesium, barium, strontium, boron, beryllium, aluminum, iron, copper, cobalt, lead and silver ions.A major problem with the above mentioned techniques of forming cross-linked PVA is that the cross-linking agents are susceptible to hydrolysis when exposed to alkali or basic conditions.
The present invention relates to the development of a hydrogel based on cross-linked PVA using an
initiator (per-sulphate ion), which has not been reported previously. Monovalent per-sulphates are
widely used in chemical industry particularly for initiating free radical polymerization reactions under
However, its role as a cross-linking agent to prepare films which can be subsequently used as hydrogels
has not been explored earlier. Per-sulphates are very cheap as compared to other agents required for
preparing hydrogels, thereby decreasing the cost enormously. There are two other advantages in this
The use of radiation for cross-linking can be avoided, and the final hydrogel is not affected by the
action of acids and bases. They maintain their strength in both alkaline and acidic medium.
OBJECTS OF THE INVENTION
The primary object of the present invention is to provide a process of forming a hydrogel film. Another object of the invention is to provide a process of forming a hydrogel film useful for wound healing applications. Yet another object of the invention is to provide a process for the preparation of hydrogel involving minimum number of steps. A further object of the invention is to provide a process for forming a hydrogel film with large water absorption capacity. Still further object of the invention is to provide a process for forming a hydrogel film with high gel content. Yet another object of the invention is to provide a process for forming a hydrogel film that is stable under both alkaline and acidic conditions. Another object of the invention is to provide a process for forming a hydrogel film that exhibits good mechanical properties.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a process for preparation of cross-linked PVA hydrogels useful for the wound healing applications, the said process comprising the steps of:
mixing an aqueous solution of a water soluble polymer with the cross-linking ion and optionally,
adding an additive to the reaction mixture; reacting the components mixed at a temperature ranging
from 50 to 100 degree C for a time period of 10 to 400 min; pouring the solution as obtained on an inert
surface; drying this solution by evaporating the solvent and finally peeling - off the dried film and
immersing it in water for about 20 minute to obtain the desired hydrogel.
BRIEF DESCRIPTION OF DRAWINGS
Figure 1 shows the relationship of intrinsic viscosity of the reaction medium containing various
amounts of potassium persulphate as a function of reaction time.
Figure 2 shows the increase in gel content with increase in reaction time.
Figure 3 and figure 4 indicate the TG/DTG traces and DSC traces for neat PVA and H-5X.
Figure 5 shows the variation of Tensile strength due to cross-linking.
Figure 6 shows the variation of Elongation due to cross-linking.
Figure 7 shows the relationship between water absorption (%) and immersion time (min).
Figure 8 shows the BSA release from PVA hydrogels.
Figure 9 shows the linear fits of the hydrogel release profiles at Mt/ Mo DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a process for forming the PVA hydrogel film, which is useful for wound healing applications. The major component for making this film is a conventional water soluble polymer like Polyvinyl alcohol. Typically PVA is prepared from polyvinyl acetate by saponification process. Depending on the initial polyvinyl acetate and hydrolysis conditions, PVA can be prepared having varying degree of hydrolysis and molecular weight.The other component for making the film is per-sulphate ion which can be associated with any monovalent ion like sodium, potassium, ammonium and the like. Both the components, i.e. water soluble polymer and per-sulphate are dissolved in water and reacted for extended time periods. These two essential components are employed in proportions such that the water-soluble polymer will constitute at least about 1% (w/v) of the total weight of composition. The content of PVA should preferably be in the range of 5 - 12 % w/v although the film can have a higher content as well. The cross-linking ion i.e. Per-sulphate will be employed in an amount constituting about 0.001 - 20 % (w/v) and most preferably 0.01 - 10 % (w/v) of the total weight of the film composition. The molecular weight of the water soluble polymer used in making film can also vary between 2000 to
3 lakhs, but preferably be in the range of 10,000 to 2,00,000.
The reaction time is in the range of 10 to 400 min when the reaction temperature is kept between 60 to
80 degree C. Both the reaction temperature and time can be varied to tailor make films of different
product specifications. The reaction time is preferably in the range of 20 to 120 min. The reaction
temperature can be varied from 50 to 100 degree C and best results are obtained between 60 to 80
Subsequently films are cast on a glass plate and the solvent is allowed to evaporate. On drying, the
films are separated from the glass trays. These dried films are then immersed in water to prepare
The novel cross-linked films can also contain other additives. By the term "additives" is meant a drug,
protein for wound healing applications, polymers containing anionic/ cationic chelating groups for ion
exchanging membranes, dyes for contact lens applications.
At -80 degree C, potassium per-sulphate leads to the generation of free radicals (SO4~), which further
react with PVA to generate tertiary radicals on the polymer chain. The films obtained are completely
transparent, however, the colors of the films become yellowish with increase in the concentration of
The reaction leads to the conversion of secondary hydroxyl groups of PVA to C=O, which can further
undergo tautomerism to form -C(OH)=C-. Regular repetition of this chromophoric group results in the
slight yellowish coloration. The insolubility of the final polymer is basically due to the reaction
between the two macro-radicals as shown in the cross-linking step.
The hydrogels based on Polyvinyl alcohol, which are prepared by chemical reaction of alcoholic groups
present in PVA with di-functional acids, anhydrides and the like lead to the formation of certain
functional groups like esters etc, in the final cross-linked structure. These ester and/or similar groups
are not resistant to acids and alkalies, as these groups are susceptible to both hydrolysis in acidic/alkali
medium. The hydrogels prepared by the present invention are obtained from the reaction of potassium
per-sulphate and PVA. The functional groups present in the final structure are carbonyl and they are not
affected by the action of acids/bases.
The mechanism for reaction of persulphate with PVA is shown:
In a preferred embodiment of the invention, the said water soluble polymer is polyvinyl alcohol, with molecular weight in the range of 10,000 to 2,00,000.
In another embodiment of the invention, the said cross-linking ion is persulphate ion, selected from the group of sodium persulphate, potassium persulphate, ammonium persulphate and any other monovalent
In another embodiment of the invention, the preferred temperature for reaction is in the range of 60 to
80 degree C.
In a further embodiment of the invention, the preferred time period for reaction is in the range of 20 to
In another embodiment of the invention, the content of said polymer is at least 1 percent (weight by
volume) and the content of said cross-linking ion is in the range of 0.001 to 20 percent (weight by
volume) of the reaction mixture.
In still another embodiment of the invention, said additive is either a therapeutic additive, a polymer
containing cationic/anionic chelating groups or a dye.
In yet another embodiment of the invention, said hydrogel is having a tensile strength in the range of 4.0
Kg/cm2 to 10.8 Kg/cm2 and percent elongation in the range of 1000 to 4500.
In another embodiment of the invention is a hydrogel, obtained by the said process.
The working examples below serve to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices, and/or methods claimed herein are made and evaluated, and therefore should not be construed to limit the scope of the invention. In the examples, unless expressly stated otherwise, amounts and percentages are by weight, temperature is in degree Celsius, or is at ambient temperature, and pressure is at or near atmospheric.
PVA (CDH, India) with a molecular weight of 14,000 was used without further purification for the preparation of hydrogels. Potassium persulphate ('AR', CDH, India) was used as a cross-linking agent. A 10% w/v aqueous solution of PVA was prepared by dissolving 10 g of PVA in 100ml water at 95 degree C for 2 hours in a rotary evaporator (Heidolph, Laborata-4003). Varying amounts of Potassium persulphate (0.1 - 0.25% w/v) were added to this solution. The reaction was allowed to proceed at 80 degree C and samples were removed at regular intervals for analysis. After 75 minutes of reaction, 20 ml of the solution was poured in petri-dishes (diameter ~ 10 cm) on a leveled platform for casting films (thickness - 1.0 mm). This was allowed to evaporate at room temperature (~ 30 degree C) for ~ 48 hours. Post drying, the films were peeled off and used for various studies after vacuum drying at 30
degree C. The details of PVA hydrogels prepared along with their sample designations have been listed
For preparation of 2% and 4% w/v Bovine Serum Albumin (BSA) loaded hydrogels, requisite amounts
of BSA (400 mg and 800 mg) was added to 20 ml of the reaction mixture after cooling it to room
temperature. The mixture was allowed to homogenize and subsequently poured into petri-dish for
Table I- Details of sample prepared along with sample of designation
(Table 1 Removed)
A 10 percent w/v aqueous solution of PVA was prepared by dissolving 10 g of PVA (Molecular weight of 14,000, degree of hydrolysis 98.5-100 percent and viscosity of 4-6 CP at 20 degree C for 4 percent aqueous solution) in 100ml of double distilled water at 95 degree C for 2 hours. Potassium persulphate was added to this solution and the reaction was allowed to proceed at 80 degree C for 75 min. The solution was poured on a glass plate for casting films (thickness ~1 mm). This was allowed to evaporate at room temperature (-30 degree C) for -48 hours. Once the film had dried, it started to separate off from the glass surface. At this stage, the film was peeled off and used for studies after vacuum drying at 30 degree C. The film was immersed in water for - 20 min and the properties were evaluated. The hydrogels had a tensile strength of 7.4 + 0.3 kg/cm2, percent elongation of 4209 + 10. The equilibrium water content was found to be 280 percent and a gel content of 100 percent.
A 10 percent w/v aqueous solution of PVA was prepared by dissolving 10 g of PVA (Molecular weight of 1,25,000) in 100ml of double distilled water at 95 degree C for 2 hours. Potassium persulphate was added to this solution and the reaction was allowed to proceed at 80 degree C for 75 minutes. The solution was poured on a glass plate for casting films (thickness ~ 1 mm). This was allowed to evaporate at room temperature (-30 degree C) for -48 hours. Once the film had dried, it started to separate off from the glass surface. At this stage, the film was peeled off and used for studies after vacuum drying at 30 degree C. The film was immersed in water for - 20 min and the properties were evaluated. The hydrogels had a tensile strength of 10.3 + 0.4 kg/cm2, percent elongation of 4000 ± 10. The equilibrium water content was found to be 300 percent and a gel content of 100 percent.
Example 4 Characterization of PVA hydrogels
The progress of cross-linking reaction was monitored by viscometry. 5 ml of the reaction mixture was removed at regular time intervals and transferred to a Ubbelohde suspension level viscometer maintained at 30 degree C for intrinsic viscosity  measurements. The data was used for Mv (viscosity average molecular weight) calculations using Mark Houwink equation.
 = 4.2 X 10-2 Mv0.64
The results as shown in figure 1, indicate the relationship of intrinsic viscosity of the reaction medium containing varying amounts of potassium persulphate as a function of reaction time. The initial  of PVA and all other formulations was 42.6 ml/g, corresponding to Mv of 48.3 x 103. It was observed that neat PVA did not exhibit any change in the intrinsic viscosity during the reaction period, while formulations containing potassium persulphate exhibited an increase which was dependent on the reaction time. Increase in the intrinsic viscosity reflects on the higher molecular weight of the polymer obtained as a result of cross-linking.
Gel content is a measure of the insolubility of the polymer and was determined by soxhlet extraction of the hydrogel with water. The cross-linked films were allowed to swell in excess water for 20 min. The swollen hydrogels were extracted with water in a soxhlet apparatus for 24 hours and then dried to a
constant weight under vacuum at 30 degree C.
The percent gel content (Gel %) was calculated gravimetrically using the following formula:
Gel % = (Wg / W0) X 100 percent
where Wg and W0 refer to weight of sample after and before extraction respectively.
The results are shown in figure 2. The gel content for formulations containing lower concentration of persulphate reached ~ 60 percent after which it leveled off, while at persulphate concentration > 0.5 percent w/v, -100 percent gel content was obtained within 60 min of reaction.
The FTIR spectra of the polymer films were recorded in the wavelength range 400 to 4000 cm"1 on a
BIORAD (HTS-40) spectrophotometer.
The FTIR spectra of PVA showed absorption bands at 3340 cm-1 and 1446 cm-1 due to O-H stretching
and O-H bonding. The reaction of PVA with persulphate did not lead to any major changes in the FTIR
spectra. There was slight increase in the absorption band at 1713 cm-1, which was due to the conversion
of hydroxyl functionalities to C=O functionalities.
The thermal behavior was investigated using Perkin Elmer Diamond STG-DTA-DSC in N2 atmosphere
(flow rate = 200 ml/min) in the temperature range of 50 to 600 degree C at a heating rate of 10 degree
C per min. A sample mass of 3 ± 0.5 mg was used in each experiment.
The TG/DTG traces and DSC traces for neat PVA and H-5X are presented in figure 3 and 4. Neat PVA
is a semi-crystalline polymer exhibiting a melting point at 229 degree C. This is immediately followed
by a decomposition step at initial decomposition temperature (IDT) of 240 degree C. On the other hand,
all the other cross-linked formulations decomposed below they reached the melting point and exhibit
double step decomposition. Moreover, the IDT was found to decrease with increase in the level of
cross-linking (150 degree C for H-1X and 143 degree C for H-25 X).
The mechanical properties of hydrogels i.e. tensile strength and elongation at break, were measured
using a tensile strength testing machine (Jragrau Instruments, JRI-TT25). Test specimens with a gauge length of 50 mm and width of 10 mm were cut from the hydrogel samples and subjected to a cross-head speed of 50 mm/min.
Both the mechanical properties tested were found to be dependent upon the degree of cross-linking. As expected, cross-linking led to an improvement in the tensile strength and decrease in elongation (figure 5 and 6). At persulphate concentrations > 1.25 percent w/v, the hydrogels became brittle and broke during handling. Optimum properties were obtained with 0.5 percent cross-linking. Hence, H-5X films were chosen for protein release studies and in-vivo studies.
Equilibrium water content
For equilibrium water content measurements, the vacuum dried films were immersed in excess water at
room temperature. The samples were removed at various intervals and weighted after removal of
surface water with filter paper. The swollen gel was then slowly dried to constant weight.
The equilibrium water content (EWC) was calculated as follows
EWC % = [(W, -Wd)/Ws] X 100 percent
where Ws and Wd refer to weight of the swollen state and dried state respectively. All the formulations absorbed water rapidly during the initial period and gained equilibrium within 20 to 30 min of immersion. Neat PVA films dissolved partially and their EWC could not be determined. However, for other samples, the water absorption was found to be dependent on the degree of cross-linking. H-1X samples absorb up to ~ 580 percent water, while H25X samples could absorb only ~ 73 percent of water (Figure 7).
Water vapor transmission rate
The water vapor transmission rate (WVTR) was determined as per the procedure reported in the
literature. The weight loss of a hydrogel capped flask containing 25ml of water was measured and the
WVTR was calculated by using the following formula:
WVTR = [(Wi -Wf) / (A X 24)] X 106 g/m2/h
where 'WVTR' is expressed in g/m2/h, 'A' is the area of bottle mouth (mm2), Wi and Wf are the weight
of bottle before and after being placed in oven for 24 hour respectively.
The WVTR values of cross-linked PVA was in the range of 170 to 180 g/m2/h. This value seems to be in
an ideal range for wound dressing. A higher value of WVTR will cause a faster drying off the wound. Though there is not an exact ideal value of WVTR for wound dressing, the value must not be so high because it will cause a dry condition in the wound areas. On the other hand, if the WVTR value is too low, it will make the accumulation of exudates, which opens up the risk for bacterial infection. Hydrogel protein release
To characterize the release of a model protein from the hydrogel, two different formulations containing BSA (2 percent and 4 percent w/v) were prepared as described earlier. Hydrogel samples of 8mm diameter were cut out from the films and carefully transferred to empty polypropylene tubes containing 15ml PBS. At specified sample collection intervals, 0.5 ml of this solution was removed and transferred to a sample vial and the test solution was replenished with 0.5 ml fresh PBS. Duplicate hydrogel test samples were analyzed in each experiment. The concentration of BSA released was determined by procedure reported elsewhere. The mass released at time i (MO was calculated from the equation:
Mi=CiV + EQ.1V! (1)
where Q is the concentration of protein in the release solution at time i, V is the total volume of release
solution and Vs is the sample volume (1 ml).
Using the Bovine Serum Albumin (BSA) release data, the Effective Diffusion Coefficient (Dc) of BSA
in PBS was analyzed according to the established methods.
For short time release [(Mi/Moo) Mi/M ~ 2[Det / 2]1/2
where Moo is the mass released at time infinity, and Mi/Moo is the fractional mass of released BSA. The fraction of protein released should be proportional to the square root of release time. The concentration of released BSA at time i and at the end of the experiment (approximation of infinite time) were used to calculate Mi/Moo, which in turn was used to calculate De using the simplified equation. For hydrogels containing BSA (2 percent and 4 percent w/v), the Mi/Moo values were plotted as a function of the square root of release time (tw) and are presented in figure 8. It can be seen that majority of the BSA was released within 5 hour. For calculation of De, the equation was applied only for the region Mi/Moo
1. A process for preparation of cross-linked PVA hydrogels, useful for the wound
healing applications, the said process comprising the steps of:
a) mixing an aqueous solution of a polyvinyl alcohol with the persulphate ion and
optionally, adding an additive;
b) reacting the components mixed in step (a) at a temperature ranging from 50 to 100
degree C for a time period of 10 to 400 min;
c) pouring the solution as obtained in step (b) on an inert surface;
d) drying the above solution by evaporating the solvant;
e) peeling - off the dried film and immersing it in water for 20-30 minute to obtain
the desired hydrogel.
2. A process for preparation of cross-linked PVA hydrogels as claimed in claim 1,
wherein polyvinyl alcohol has molecular weight in the range of 10,000 to 2,00,000.
3. A process for preparation of cross-linked PVA hydrogels as claimed in claim 1,
wherein the persulphate ion is selected from the group of sodium persulphate,
potassium persulphate, ammonium persulphate and any other monovalent persulphate
4. A process for preparation of cross-linked PVA hydrogels as claimed in claim 1,
wherein the temperature for reaction in step (b) is in the range of 60 to 80 degree C.
5. A process for preparation of cross-linked PVA hydrogels as claimed in claim 1,
wherein the time period for reaction in step (b) is in the range of 20 to 120 minute.
6. A process for preparation of cross-linked PVA hydrogels as claimed in claim 1,
wherein the said polymer in step (a) is in the range of 1-10 percent (weight by
volume) and the said cross-linking ion in step (a) is in the range of 0.001 to 20
percent (weight by volume) of the reaction mixture.
7. A process for preparation of cross-linked PVA hydrogels as claimed in claim 1,
wherein said additive is either a therapeutic additive, a polymer containing
cationic/anionic dictating groups or a dye.
8. A process for preparation of cross-linked PVA hydrogels as claimed in claim 1,
wherein said hydrogel is having a tensile strength in the range of 4.0 kglcm2 to 10.5
kglcm2 and percent elongation in the range of 1000 to 4500.
9. A hydrogel, useful for the wound healing applications, obtained by the process as
claimed in claim 1.
|Indian Patent Application Number||1281/DEL/2007|
|PG Journal Number||52/2013|
|Date of Filing||14-Jun-2007|
|Name of Patentee||THE DIRECTOR GENERAL, DEFENCE RESEARCH & DEVELOPMENT ORGANISATION|
|Applicant Address||MINISTRY OF DEFENCE, GOVERNMENT OF INDIA,AN INDIAN GOVERNMENT ORGANISATION, DRDO BHAWAN, NEW DELHI-110011|
|PCT International Classification Number||B29D11/00|
|PCT International Application Number||N/A|
|PCT International Filing date|