The present invention relates to the use of peptides which are derived from zona pellucida proteins and are used for contraception, and pharmaceutical formulations which contain the peptides without the peptides having an immunogenic effect.

This invention relates to the use of peptides that are derived from zona pellucida proteins for contraception and for pharmaceutical formulations that contain these peptides, without these peptides having an immunizing action.
With the increase in world population, the need for efficient methods of contraception is also growing. In addition to oral contraceptives and spermicides, mechanical contraceptives are also available here, such as, for example, IUDs (intrauterine devices), vaginal rings, and condoms. Another approach is based on preventing fertilization by blocking the egg-sperm interaction. The sperm must penetrate the zona pellucida, an extracellular matrix that consists of glycoproteins and that surrounds the female gametes (the growing oocytes and the ovulated egg). This interaction takes place via a complex interplay of ligands, as well as sperm receptors on the part of the ovocyte or the sperm surface. The zona pellucida of the various mammalian species consists of three to four glycoproteins, which are normally referred to as ZP1, 2, and 3 or ZPA, B and C [Harris, J. et al.: Cloning and Characterization of Zona Pellucida Genes and cDNA""s from Variety of Mammalian Species: The ZPA, ZPB and ZPC Gene Families. DNA Sequence: 4, 361-393, (1994)]. In mice, it has been described that the sperm bond first to ZP3 via O-bonded oligosaccharide chains, and the additional bond is probably mediated by ZP2. ZP3 seems to mediate not only the initial bond of the sperm to the zona pellucida, but also another decisive process for fertilization, the acrosome reaction [Dean, J.: Biology of Mammalian Fertilization. J. Clin. Invest.: 89, 1055-1059 (1992); Wassermann, P. M.: Regulation of Fertilization by Zona Pellucida Glycoproteins. J. Reprod. Suppl.: 42, 79-87, (1990)].
In view of the fact that the zona pellucida glycoproteins are unique in the ovary, exhibit antigenic properties, and are accessible to circulating antibodies during the intraovarian growth phase, the research has focused on the development of contraceptive vaccines on the basis of zona pellucida proteins [Naz, R. K. et al.: Development of Contraceptive Vaccines for Humans Using Antigen Derived from Gametes (Spermatozoa and Zona Pellucida) and Hormones (Human Chorionic Gonadotropin): Current Status. Human Reprod. Update: 1, 1-18, (1995); Millar, S. E. et al.: Vaccination with Zona Pellucida Peptides Produces Long-Term Contraception in Female Mice. Science: 246, 935-938, (1989)]. A phenomenon that was noted in almost all animals in the case of immunization with zona pellucida proteins is the induction of an oophoritis. Previously it was not possible to completely explain the reason for the occurrence of an oophoritis. In any case, the formation of an oophoritis makes the longer-term use of zona pellucida proteins or of peptides that are derived from these proteins appear problematical for contraceptive immunization.
There is therefore an urgent need for a new contraceptive that actively prevents fertilization by blocking egg-sperm interaction, without having an immunizing action.
It has now been found that the egg-sperm interaction is prevented by peptides that are derived from zona pellucida proteins.
This invention relates to the use of peptides that are derived from zona pellucida proteins for contraception, without these peptides having an immunizing action.
In another embodiment, this invention relates to the use of peptides that are derived from zona pellucida proteins, for the production of pharmaceutical formulations.
In another preferred embodiment, the peptides are derived from mouse protein or human ZP1, 2, or 3 protein.
In an especially preferred embodiment, peptides are derived from mouse protein or human ZP3 proteins.
In another especially preferred embodiment, the peptides are
-RYPRQGNVSS-xe2x80x83xe2x80x83(SEQ ID NO:1)
-TPSPLPDPNSSPY-xe2x80x83xe2x80x83(SEQ ID NO:2)
-SRNRRHVTDEADVT-xe2x80x83xe2x80x83(SEQ ID NO:3)
-CSNSSSSQFQIHGPR-xe2x80x83xe2x80x83(SEQ ID NO:4)
-TRKCHSSSYLVSLPQ-xe2x80x83xe2x80x83(SEQ ID NO:5)
-SQFQIHGPRQ-xe2x80x83xe2x80x83(SEQ ID NO:6)
-TPT..PDQNASPY-xe2x80x83xe2x80x83(SEQ ID NO:7)
-CGTPSHSRRQPHVMS-xe2x80x83xe2x80x83(SEQ ID NO:8)
-SRNRRHVTEEADVT-xe2x80x83xe2x80x83(SEQ ID NO:9)
-TRRCRTASHPVSASE-xe2x80x83xe2x80x83(SEQ ID NO:10)
xe2x80x83-SRRQPHVMSQ-xe2x80x83xe2x80x83(SEQ ID NO:11)
In another especially preferred embodiment, the peptides are
-RYPRQGNVSS-xe2x80x83xe2x80x83(SEQ ID NO:1)
-TPT..PDQNASPY-xe2x80x83xe2x80x83(SEQ ID NO:7)
-SRNRRHVTDEADVT-xe2x80x83xe2x80x83(SEQ ID NO:3)
-TRRCRTASHPVSASE-xe2x80x83xe2x80x83(SEQ ID NO:10)
-SQFQIHGPRQ-xe2x80x83xe2x80x83(SEQ ID NO:6)
The synthesis of peptides was carried out according to Fmoc strategy [Carpino, L. A. and Han, G. Y. (1970) J. Amer. Chem. Soc. 92:5748-5749; Carpino, L. A. and Han, G. Y. (1972) J. Org. Chem. 37:3404-3409] on solid vehicles [Merrifield, R. B., (1963) J. Am. Chem. Soc. 85, 2149] on an automatic peptide synthesizer. Should the peptides carry a free C-terminus (COOH), HMP-resin [Wang, S. -W. (1973) J. Am. Chem. Soc. 95, 1328] would be used for the synthesis. Should the C-terminus be amidated (CONH2), Rink amide resin [Rink, H., (1987) Tetrahedron Lett. 28, 3787] would be used. Should the peptides N-terminally carry a free amino group (H2N-), the Fmoc protective group would be cleaved in the last synthesis cycle. Should the N-terminus be acetylated (Ac-), however, the amino group of the N-terminal amino acid could be reacted with acetic anhydride after Fmoc cleavage.
The cleavage of the protective groups was carried out for 0.1-1.5 g of peptide resin with:
0.75 g of phenol,
0.25 ml of ethanedithiol,
0.5 thioanisole
0.5 ml of H2O
10 ml of trifluoroacetic acid
and three hours of incubation while being stirred at 37xc2x0 C. in a water bath.
Peptide isolation was carried out either by precipitation with tert-butylmethyl ether cold (ice bath) and subsequent centrifuging, or after spinning-in in a vacuum by precipitation with ether and subsequent filtering. After drying, the peptides were purified via HPLC as needed.
I. In Vitro Fertilization
In vitro fertilization represents a test system that makes possible a first review of a contraceptive effect of substances. In this case, the possibility exists of studying whether the contraceptive effect can be attributed primarily to an inhibition of the sperm function(s) or to an inhibiting effect on the oocytes, or to the two above-mentioned effects.
I.1. Animal Material
Fertile female mice (CB6F1 strain) about 12 weeks of age; fertile male mice (CB6F1 strain) at least 14 weeks of age.
I.2. Preparation and Execution
Pyrex and bulb bottles are autoclaved.
The medium according to Brinster, Whitten and Wittingham
The medium is then set at pH 7.4 with 0.5 M NaOH.
Sterile bulb bottles are exposed to gas with carbogen for 5 minutes, and the medium is then filtered into the latter (with a shelf life of no more than one week at 4xc2x0 C.). To equilibrate the oil, 100 ml of paraffin oil (uvasol) is heated for 2 hours at 100xc2x0 C. and finally cooled. After cooling, 20 ml of BWW/0.3% BSA is added and exposed to gas for 20 minutes with carbogen.
All instruments that are to be used are sterilized overnight at 140xc2x0 C. The incubator is set at 37xc2x0 C., 5% CO2, and 95% O2.
The small Petri dishes:
a) are filled with paraffin oil that is exposed to carbon gas and kept warm at 37xc2x0 C. to produce oocytes.
b) are pipetted onto the bottom of the small dish with 0.5 ml of BWW/2% BSA for sperm capacitation (prepared before the removal of the tubes), covered with equilibrated oil, and kept at 37xc2x0 C.
c) 0.1 ml of BWW/0.3% BSA, corresponding to the concentrations that are to be tested, is mixed with or without substance (control) for the fertilization (prepared after removal of the tubes), covered with equilibrated oil, and kept at 37xc2x0 C.
I.2.1. Induction of Superovulation
10 injection units of PMS/0.1 ml are injected intrapericutaneously into the approximately 12-week-old fertile mice, and 54 hours later, 10 injection units of HCG/0.1 ml are administered.
I.2.2. Recovering Sperm
a. In Mice
To recover sperm, a mouse buck is sacrificed, and the two epididymal appendages are removed and transferred into the prepared small Petri dishes [see above under b)]. The tissue parts are cut in the medium, so that the sperm can escape. The sperm are capacitated for one hour in the incubator. After the capacitation time has been completed, the sperm are diluted 1:5 with BWW/0.3 BSA. For counting in the counting chamber, a 1:1 aliquot is diluted with doubly distilled H2O. The desired sperm concentration is 40,000-80,000/0.1 ml.
b. In Humans
For the zona bonding test in humans, the ejaculate of normo-zoospermatocidal donor semen is prepared with use of SpermFertil(R) glass wool columns (Mello Ltd., FRG). The filtrates were washed and resuspended in HFT-HSA (HFT=human tubal fluid medium according to Quinn et al., supplemented with 10 mg/ml of human serum albumin=HSA).
I.2.3. Recovery of Oocytes
a. In Mice
The animals are sacrificed 13 hours after the HCG injection, and the tubes are removed and transferred into the prepared small Petri dishes [see above under a)]. Pending further processing, the small dishes are kept at 37xc2x0 C. on the warming plate. Under the stereomicroscope, the tubes that are in oil are pulled apart. In this case, the cumulus clouds pour out, which then are transferred into the prepared medium drops (two cumulus clouds per drop).
b. In Humans
All human oocytes are obtained from post mortem material. Provision is made at all times to ensure that all legal, ethical and moral guidelines during the entire process are strictly followed.
Unless otherwise indicated, the oocytes are stored in 36.6 mmol of HEPES buffer, pH 7.4, which contains 1.5 M MgCl2 and 0.1% PVP at 4xc2x0 C.
I.2.4. In Vitro Fertilization
0.1 ml of dilute sperma-defined concentration is added to the oocytes that are in the medium drops and is incubated for 24 hours in the incubator at 37xc2x0 C.
I.3 Evaluation
After incubating for 24 hours in the incubator, the following parameters are computed:
a) Number of complete oocytes
b) Number of divided oocytes
c) Number of undivided oocytes
d) Number of degenerated oocytes.
The fertilization rate corresponds to the number of divided oocytes per total number of intact oocytes.
II. Zona Bonding Assay
The sperm and oocytes are obtained as described in in vitro fertilization.
The oocytes that are obtained as under I.2.3. are taken up by a finely drawn Pasteur pipette, whose diameter must be somewhat smaller than the diameter of the oocytes, with a few xcexcl of BWW medium. This process is repeated several times and finally causes the zonae pellucida to burst. The cytoplasmic portion of the ooctyes is released, and the isolated zona pellucida is collected for further tests and covered in 0.1 ml of BWW medium with equilibrated oil and kept at 37xc2x0 C.
II.1 Zona Pellucida Bonding Test
a) In Mice
The capacitated mouse sperm (see I.2.2) are preincubated for 15 minutes either with a solvent or the desired substance, and then 0.1 ml drops are added to the isolated zonae pellucidae, in such a way that the incubation volume is a total of 0.2 ml (under oil). About 20 zonae pellucidae are studied per drop. The sperm concentration per drop is between 10,000 and 30,000 per xcexcl. Sperm and zonae are incubated for 45 minutes in an incubator (see Description under I.2). After the incubation period, the number of bonded sperm per zona is evaluated under an inverse microscope. The upper limit of the sperm, which have yet to be counted exactly, is 20 sperm per zona pellucida under control conditions.
b) In Humans
The experiments consist of three incubation drops that contain 10 xcexcl of a standard HTF-HSA medium (see above) and 40 xcexcl of working medium (see below). A specific number of oocytes (for TEM) or hemizonae for the bonding was added to each drop to ensure bonding. For the bonding experiments, a 10 xcexcl sperm drop (50xc3x97106/ml) was added to each drop, covered with mineral oil, and incubated for 4 hours at 37xc2x0 C. in 5% CO2. The statistical evaluation was done according to the non-parametric Mann-Whitney two-sample test.
Composition of the working medium: 20 xcexcl of 5 mmol NaH2PO4 (adjusted with phosphoric acid), pH 2.5, plus 20 xcexcl of a specially composed doubly-concentrated HTF-HSA medium, mixed at a ratio of 1:1 (vol/vol).
Composition of the doubly-concentrated HTF-HSA medium:
Application
The above-mentioned peptides can be used in different pharmaceutical products.
Peptides can be administered invasively (intravenously, intramuscularly, subcutaneously, subdermally) and non-invasively (topically, orally). To achieve a lasting effect, long-term applications are of special advantage.
a) Formulation of Peptides as Microcapsules
Copolymers of lactic acid and glycolic acid are often used as microencapsulating material. This compound embeds the peptide. The microcapsules themselves are suspended in liquid waxes and oils such as isopropyl myristrate or castor oil.
b) Formulation as Salts
Basic cationic peptides can also form salts with anionic polymers, such as polyester, which are water-insoluble and are therefore suspended in a stable manner in aqueous vehicles.
c) Biodegradable Implants
The materials that are mentioned under a) and b) can also be extruded or pressed. Large shaped bodies are produced, which represent subdermal active ingredient deposits for use for periods of 6 months to 6 years.
d) Liposomes can also be used as vehicles for peptides. The shell is preferably made of phosphatidylcholine and cholescol and optionally other components that are largely impermeable to the active ingredient. Thus, the latter is optimally protected. The liposomally encapsulated peptides can be administered both inversively and topically or orally.
e) TDS are especially suitable for the indication provided. They are used for, e.g., 7 days, and release the active ingredient constantly. As a skin contact adhesive, all commonly used silicone and acrylate adhesives can be used. The addition of a commonly used enhancer to cross the skin barrier may be important. The formulation principle can be used up to a molecular weight of 1000 Dalton and thus is especially suitable for the peptides that are described.
f) Mucous membrane-adhesive systems are suitable especially for transmucosal and transnasal use. As is generally known, this barrier with peptides is easier to cross than the skin. In addition, enhancers can be used here. As forms of administration, powders and solutions (sprays) and ointments of all types are suitable.
g) As already reported under f), peptides find it difficult to pass through the skin, and use as creams, gels or ointments is possible in the uncharged state for smaller molecules. Disposable packages are desirable with a view to safer use.
h) Charged peptides can be administered into the skin using iontophoresis. A corresponding device consists of 2 parts, a donor-gel side with electrodes and a counterpol, where the active ingredient is delivered to the skin with donor voltage applied.
Other pharmaceutical formulations are possible with the commonly used adjuvants and vehicles.

Zona pellucida proteins for contraception


What is disclosed is the preparation and use of synthetic water soluble copolymers useful in modifying the water permeability characteristics of subterranean hydrocarbon producing formations. The copolymers are in the form of dilute, pumpable, homogeneous, aqueous solutions and comprise a crosslinked synthetic copolymerizate with intramolecular and intermolecular crosslinking in a non-gelled state and a molecular size/shape corresponding to a K-value of 220-450.

The invention pertains to the preparation and use of synthetic water soluble copolymers useful in modifying the water permeability characteristics of subterranean hydrocarbon producing formations.
Water and oil or gas often exist in the same or adjacent formations. This water is often co-produced with the desired oil or gas, leading to operational problems. As water is produced and removed from the formation, the hydrostatic pressure within the formation that is exerted on the hydrocarbon content decreases, contributing to a decline in hydrocarbon production rates. Once above ground, the produced water must be separated from the sought-after hydrocarbon. Frequently, the water exists in an emulsion with the hydrocarbon, necessitating efforts to break the emulsion and remove the water fraction. The produced water also requires storage and/or disposal, which is often time consuming and expensive.
Efforts to minimize produced water and its associated problems are addressed conventionally in the art by the use of natural, semi-synthetic, and synthetic crosslinkable polymer solutions or dispersions. Synthetic water soluble or dispersible copolymers have been successfully used for so-called water shut-off purposes as well as in relative permeability modification applications (hereinafter for short, xe2x80x9cRPMxe2x80x9d). These methods involve the reduction in the flow of subterraneous water in the horizons with oil and/or gas near the well-bore. The use of water shut-off polymers thus leads to a stoppage of water feeds to a production well-bore, but usually also leads to a stoppage or significant reduction in hydrocarbon production in the treated zone. The present invention is directed mainly to RPM, wherein the permeability of water in the formation is minimized without causing a significant decline in oil and/or gas permeability.
In the conventional methods, crosslinkable polymers in aqueous solutions or dispersions are pumped into underground formations and undergo swelling and crosslinking reactions to develop desired gelation characteristics. The polymer adsorbs onto the porous solids, and the gel holds water within the gel structure to alter the migration behavior and reduce the amount of produced water. Conventionally, an aqueous solution containing a crosslinkable polymer is pumped into water and hydrocarbon producing formations so that they enter water zones within and adjacent to the formations. Crosslinking materials may is either be injected along with the crosslinkable polymer solution, or injected after the polymer has been injected.
The art includes various techniques and chemistries for achieving the desired subterranean swelled, crosslinked gels of the polymer solutions, generally leading to the formation of substrate-adhered gels which reduce or stop, as the intended result, the flow of water through the natural fractures and high permeability streaks in the formations.
Early examples of synthetic polymers are the partially hydrolyzed polyacrylamides possessing pendant carboxylate groups reactive with external crosslinking agents. Thermally stable, crosslinkable, carboxylate-containing polymers of acrylamide; copolymers of N-vinyl-2-pyrrolidone and acrylamide; terpolymers of sodium-2-acrylamido-2-methyl-propanesulfonate, acrylamide, and N-vinyl-2-pyrrolidone; and copolymers of sodium-2-acrylamido-2-methyl-propanesulfonate, acrylamide, and vinylacylamide have been suggested for use with an external crosslinking system to treat subterranean formations with high salinity and at elevated temperatures.
In the conventional method of altering the permeability of water in underground formations, the crosslinkable polymers are injected into a formation simultaneously with a selected crosslinking system, each typically in the form of aqueous solutions. The solutions permeate into the regions having the highest water permeability, crosslinking reactions proceed over the course of hours, resulting in an aqueous, (swelled) gel. Thermosetting phenol-aldehyde polymers are exemplary crosslinking systems used in combination with water-soluble crosslinkable polymer. Other crosslinking agents include multivalent metal compounds reactive with carboxyl-containing copolymers, for example, complexed chromium, zirconium, or titanium compounds. Complexing ligands are sometimes also utilized and are effective in delaying the onset of gelation.
Use is often made of polymers that are introduced in a solution into the porous formations, absorbed at the solid surfaces and penetrate into the pores so that they are suitable for reducing the water influx by friction.
U.S. Pat. No. 4,095,651 discloses the use of hydrolyzed polyacrylamides. It has been found, however, that this polymer type is mainly effective for water with a low salt content and breaks down in water with a higher salt content. In the presence of polyvalent ions these polymers have a tendency at high temperatures to form precipitates that can clog the pores of the rock formations.
U.S. Pat. No. 4,507,440 discloses water soluble polymers for enhanced petroleum recovery which are crosslinkable on addition of acid, resulting in crosslinks of the xe2x80x94NRxe2x80x94CHxe2x95x90Nxe2x80x94COxe2x80x94 type. These polymers are employed in acidizing-stimulation of underground oil and gas formations. The polymers contain copolymerized acrylamide and formyl-amido-type comonomers. Thus, in-situ (underground) crosslinking in the well bore-hole occurred by co-injection of aqueous 15 wt. % HCl containing a mixture of water soluble copolymers, one being a copolymer of 2-acrylamido-2-methylpropanesulfonic acid-acrylamide-N-vinyl-N-methylacetamide and the other being acrylic acid-vinyl formamide-vinyl pyrrolidone copolymer. The crosslinked polymer gels are stable for days at 20-30xc2x0 C. in acid media, but are easily hydrolyzed at 80-90xc2x0 C.
U.S. Pat. No. 4,718,491 discloses the use of polysaccharides. These compounds, which are difficult to inject into the pore space, do effect a retardation or reduction of the water influx, but they allow only incomplete exploitation of the hydrocarbon deposits. They have been known to lose their effect at high temperatures.
U.S. Pat. No. 4,842,971 discloses the use of non-hydrolyzed acrylamide polymers or copolymers which are hydrolyzed by the subsequent introduction of an aqueous basic solution. This process has some drawbacks in terms of additional work for introducing a further solution in the well-bore and difficulties attendant in reaching the injected polymer solution by subsequent application of the basic solution. Corrosion of equipment from basic solutions are known. In addition, the efficacy of the polymer solution is contingent upon the extent of hydrolytic conversion by the basic solution.
Other examples of conventional methods and materials include those disclosed in U.S. Pat. No. 5,547,025. Therein, carboxylate-containing, water swellable polymers capable of gelling in the presence of crosslinking agent such as, for example, a multivalent metallic compound are exemplified.
U.S. Pat. No. 5,379,841 discloses methods for reducing or stopping water inflow from a deposit with the use of a copolymer comprising 2-acrylamido-2-methylpropane sulfonate and vinylacylamide, with optional anionic or cationic comonomers. The molecular weight of the copolymers can range from 50 thousand to 20 million. Optional anionic or cationiccomonomers are suggested for desired increased adhesion to different substrates. For formations in which pore diameters are smaller, molecular weights of the copolymer are suggested to be in the range of 50,000 to 3 million, and for formations having relatively larger diameter pore sizes, a molecular weight in the range of 3 to 20 million is suggested.
U.S. Pat. No. 5,701,956 teaches the use of a graft copolymer of a hydrophilic polymer and a phosphonate as a crosslinkable aqueous polymer in brine. The latent crosslinking function is selective to the water phase and not the oil phase. Polymer compositions for which phosphonate functional compounds are grafted thereto include polyacrylamide, copolymers containing acrylamide, partially hydrolyzed polyacrylamide and related copolymers, hydroxyalkylcelluloses, guar gum and derivatives thereof and other similar hydrophilic polymers. The latent or post-crosslinking function comprises a phosphonate salt or phosphonic acid monomer. The phosphonate in the graft copolymer crosslinks with the divalent metals in alkaline formation materials at pH levels above 7.
WO 98/06929 discloses compositions and RPM methods wherein a dispersion of (sub)micron-sized, water-swellable, cross-linked polymer particles is used to form a treatment fluid. The treatment fluid containing the water-swellable particles is injected into the subterranean formation. The excessive size constraint of the particles is overcome by using invert polymer emulsion or microemulsion processes to provide particles that are smaller in size than so-called super absorber particles, and smaller than that of the formation pore structures. Upon injection of a saline dispersion of the particles, optionally along with an inverting surfactant, the particles become trapped in the formation, and upon flow back of water, the particles swell in size and absorb into the formation. Thus a dispersion of small particles of a copolymer made from the emulsion polymerization of acrylamide, acrylic acid, methylene bisacrylamide, and dimethyldiallyl ammonium chloride are injected into subterranean formations where swelling takes place, restricting further water flow.
While crosslinkable and crosslinked, water-swellable copolymers, such as the above, are adapted in the state of the art for water permeability modification of subterranean formations, varying degrees of success are achieved due mainly to variable subterranean conditions, the physico-chemical response of the copolymers to these conditions, and the particle size of the dispersed copolymers. The conventional approach employs dispersed particles of copolymers containing selected monomers providing water swelling and/or crosslinking sites which activate when injected underground. The time-rate and extent of development of ultimately useful properties of copolymers after introduction underground is not exact. On interaction with the underground conditions, the development of useful properties such as substrate adhesion, water swelling, and gelation properties, and the effect of these developed properties on reducing water production and the extent of avoiding blockage of oil or gas flow, and other significant performance parameters, can be a matter of trial and error. A particular copolymer, or a particular form of a given copolymer, found useful for certain subterraneous formations may not develop the same properties or be as useful in other formations.
The insertion in the formation of an impenetrable barrier between the water and the well-bore or between the water and the oil or gas can block just as much oil or gas as water. The blockage components can be: cement, resins, suspensions of solid particles, paraffins or water-soluble polymers which become cross-linked in the subterranean formations. Prior to injection of such water shut-off treatments, it is often necessary to determine the location of the regions in the formation that are producing the undesired water. The water shut-off treatment must then be specifically placed in the targeted zones via zonal isolation techniques to avoid the unintentional placement of the water shut-off material in zones that produce substantial quantities of hydrocarbon.
A gelled solution of copolymer has a relatively extensive intermolecular network of crosslinking and is not useful for infusion into most porous subterranean formations, as the polymer fails to yield to the stress applied by conventional pumping pressures to adequately flow through the throats of the pore passageways. On the other hand, aqueous dispersions of micro-particles which are injected in an unswelled state, must be inverted on-site and injected in order to provide adequate penetration into subterranean pores which are only greater in diameter, and obviously, incomplete penetration is possible due to variations in the distribution of polymer particle size, salinity, changes in particle size over time, as well as the distribution of pore sizes in any given formation.
Solutions of crosslinkable polymers of relatively low molecular weight can be completely distributed throughout the porous formations, but lack sufficient permeability modifying properties unless further steps such as providing in-situ crosslinking are provided. Therefore a continuing need exists for improved material compositions and methods capable of selectively reducing the relative rate of water production from subterranean zones and oil and/or gas formations of varying degrees of porosity and pore sizes, and it would be of industrial importance to achieve RPM results with or without the need for insitu crosslinking.
In one aspect of the present invention there is provided a dilute, pumpable, homogeneous, non-gelled aqueous solution of a relative permeability modifying copolymer comprising a crosslinked synthetic copolymerizate, which has a balance of intramolecular and intermolecular crosslinking, that is readily injectable into the pores of subterranean formations under pumping pressures (injectivity) and that is characterized by having a molecular size/shape corresponding to a K-value of 220-450. The term xe2x80x9ccrosslinkedxe2x80x9d is used herein to describe a copolymer that is randomly, and uniformly crosslinked prior to injection into the well-bore. The term xe2x80x9cinsitu crosslinkingxe2x80x9d refers to the optional further crosslinking of some embodiments of the crosslinked copolymer of the present invention, such further crosslinking taking place after injection into the subterranean formation.
In another aspect there is provided the process for modifying the permeability of subterranean water-producing formations comprising the injection of dilute homogeneous aqueous solutions of a crosslinked, anionic copolymerizate comprising a major amount ( greater than 50% by weight) of copolymerized acrylic amide and sulfonated vinyl comonomer and a particular amount of nonionic crosslinking monomer to provide a copolymerizate which forms a homogeneous aqueous solution and a K-value as specified above.
In another and preferred aspect, there is provided an anionic, crosslinked, water-soluble, synthetic copolymer which forms a homogeneous, aqueous readily flowable solution under reasonably achieved pumping pressures, the copolymer comprising greater than 50% by weight of three copolymerized comonomer components: sulfonated vinyl monomer, N-substituted xcex1,xcex2-unsaturated carboxylic amide, and an effective amount of polyethylenic unsaturated copolymerizable comonomer (XL), such amount of XL selected to provide a random and uniformly crosslinked copolymer characterized by having a K-value in the range of from 220-450.
In another aspect, there is provided an aqueous, dilute, agitated solution polymerization method for making anionic, crosslinked, water-soluble, synthetic copolymerizates resulting in a readily pumpable and injectable, homogeneous, aqueous solution, said copolymer having a K-value, measured according to the test specified hereinbelow in the range of from 220-450, and preferably a K-value of from about 230 to about 300, and most preferably K-value of 240 to 290.
In yet a further aspect there is provided an amphoteric copolymer comprising either of the above anionic copolymers including further, a minor amount ( less than 50% by weight) of a cationic comonomer.
In one aspect, the crosslinked, water-soluble anionic copolymer which forms a non-gelled, homogeneous aqueous solution, according to the invention, comprises the following incorporated randomly as a copolymerizate:
(A) 1% to 90%, preferably 20% to 75%, more preferably, 30% to 65%, by weight of comonomer units (1) having the copolymerizable structure represented by (1):
wherein Rxe2x80x2 is hydrogen or methyl, ethyl, propyl or butyl, and Rxe2x80x3 and Rxe2x80x2xe2x80x3 are independently hydrogen, methyl, ethyl, propyl or butyl,
(B) comonomer units (2) are incorporated at 1% to 75% by weight, preferably 10% to 60% by weight,
xe2x80x83more preferably 20% to 50% by weight having the copolymerizable structure represented by (2):
wherein R1 is hydrogen or methyl and R2 is a sulfo, sulfophenyl, sulfoalkyl, sulfoalkyl amido, (collectively, xe2x80x9csulfo groupsxe2x80x9d), or phosphonic acid (xe2x80x94PO3 2xe2x88x92) (phosphono) group, including sodium, potassium, ammonium, calcium, magnesium and partial salts or mixed salts. Alternatively (2) can be comprised of a mixture of two or more different monomers containing sulfo and/or phosphono groups. The R2 alkylene units contain C2-C10 groups, or alkyl benzyl groups containing C7-C16 carbon atoms, including mixtures thereof;
(C) from 0.01% by weight to 2% by weight on total weight of comonomers of a copolymerizable crosslinker either as a copolymerized comonomer, or crosslinked during and/or after copolymerization.
Optional, but preferred comonomers include vinylacylamides having the structure
wherein R3 is hydrogen, methyl, or ethyl, R4 is hydrogen, methyl or ethyl, R5 is hydrogen, methyl, or ethyl; and optionally R4 and R5 form a cyclic amide. Comonomer (3) is incorporated at a level generally of from 1% to 50%, more particularly, from 2% to 40%, and more preferably, from 5% to 30% by weight on total comonomer weight.
The vinylacylamide comonomers suggestive of (3) include, but are not limited to N-vinyl acetamide, N-vinyl-N-methyl acetamide, N,N-dimethyl acetamide, N-vinyl-2-pyrrolidone, N-vinyl formamide (VF), and N-ethenyl-N-alkyl acetamide, and mixtures of two or more of such comonomers.
The comonomer according to (1) is the recognized class of N-substituted xcex1,xcex2-unsaturated carboxylic amides including any two or more thereof.
Representative preferred comonomer units according to (1) incorporated into the crosslinked copolymer, in amounts of from 1 to 90% by weight, preferably 20 to 75%, most preferably 30 to 65% by weight of the copolymer, are represented by
wherein R7 is selected from the group consisting of hydrogen and alkyl groups containing from 1 to 4 carbon atoms, acrylamide (AM) being the most preferred comonomer according to (1xe2x80x2). Other comonomers representative of (1) or (1xe2x80x2) include N-t-butyl acrylamide, N-cyclohexyl acrylamide, higher alkyl amides, where the alkyl group on the nitrogen contains from 8 to 32 carbon atoms. Acrylic amides include N-alkylol amides of alpha, beta-olefinically unsaturated carboxylic acids and having N-alkyl groups of from 4 to 10 carbon atoms such as N-methylol acrylamide, N-propylol acrylamide, N-methylol methacrylamide, N-methylol maleimide, N-methylol maleamic acid esters, N-methylol-p-vinyl benzamide, and the like.
The class of monomers representative of (2) are sulfonated and phosphono vinyl monomers. Representative of this class are vinyl sulfonate acid and salt (e.g., xcex1-olefin sulfonate), 2-acrylamido-alkyl sulfonic acid, including salts, vinyl sulfonic acid, salts of vinyl sulfonic acid, vinyl benzene sulfonic acid, salts of vinyl benzene sulfonic acid, allyl sulfonic acid, salts of allyl sulfonic acid, methallyl sulfonic acid, salts of methallyl sulfonic acid, 3-methacrylamido-2-hydroxypropyl sulfonic acid, salts of 3-methacrylamido-2-hydroxypropyl sulfonic acid, and vinyl phosphonic acid, and combinations of two or more thereof; wherein said salts are salts of a cation selected from the group consisting of sodium, potassium, ammonium, calcium and magnesium.
Preferred comonomers according to (2) are the acrylamido alkyl C2-C10-alkylene, preferably C2-C6-alkylene, more preferably C4-alkylene sulfonates.
The most preferred representative of (2) is 2-acrylamido-2-methylpropane sulfonate (AMPS) which has the structure (2xe2x80x2)
In the preferred copolymerizate, there is a mixture of the sulfonic acid and ammonium salt, in a relatively neutral pH from about 6 to 8, preferably around 7.
The most preferred optional comonomer incorporated randomly during polymerization at a level of from 10 to 30% by weight of the resulting crosslinked copolymer is a vinylacylamide monomer of the formula (3xe2x80x2)
wherein R1 is hydrogen and R2 is hydrogen, methyl or ethyl.
The copolymers optionally can have randomly incorporated carboxylic acid comonomer, such as the olefinically-unsaturated carboxylic acids containing at least one activated carbon-to-carbon olefinic double bond, and at least one carboxyl group; that is, a carboxylic acid or another functional group that is readily converted to a carboxylic acid and containing an olefinic double bond reactive in polymerization because of its presence in the monomer molecule, either in the alpha-beta position with respect to a carboxyl group, xe2x80x94Cxe2x95x90Cxe2x80x94COOH; or as part of a terminal methylene grouping, H2Cxe2x95x90C less than .
Olefinically-unsaturated acids of this class include such materials as the acrylic acids, e.g., acrylic acid itself, alpha-cyano acrylic acid, beta methylacrylic acid (crotonic acid), alpha-phenyl acrylic acid, beta-acryloxy propionic acid, cinnamic acid, p-chloro cinnamic acid, 1-carboxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaric acid, and tricarboxy ethylene, and the like. As used herein, the term xe2x80x9ccarboxylic acidxe2x80x9d includes the polycarboxylic acids and those acid anhydrides, such as maleic anhydride, wherein the anhydride group is formed by the elimination of one molecule of water from two carboxyl groups located on the same carboxylic acid molecule. Maleic anhydride and other acid anhydrides useful herein have the general structure wherein R and Rxe2x80x2 are selected from the group consisting of hydrogen, halogen and cyanogen (xe2x80x94Cxe2x89xa1N) groups and alkyl, aryl, alkylaryl, arylalkyl, and cycloalkyl groups such as methyl, ethyl, propyl, octyl, decyl, phenyl, tolyl, xylyl, benzyl, cyclohexyl, and the like.
The preferred optional carboxylic acid comonomers are the monoolefinic acrylic acids having the general structure
wherein R2 is a substituent selected from the class consisting of hydrogen, halogen, and the cyanogen (xe2x80x94Cxe2x89xa1N) groups, monovalent alkyl radicals, e.g., methyl, ethyl, etc., monovalent aryl radicals, monovalent aryl substituted alkyl radicals, monovalent alkyl substituted aryl radicals, and monovalent cycloaliphatic radicals. Of this class, acrylic (AA) and/or methacrylic acid are most preferred.
The copolymers can optionally be phosphonated by way of a copolymerizable phosphonic acid-containing monomer, such as vinyl phosphonic acid, methylvinyl phosphonic acid, polyvinylphosphonic acid, and their salts (referred to as phosphonates) or by reaction of the copolymer with a phosphonating agent such as phosphorus trichloride.
The copolymers contain comonomers that provide reactive sites for further optional external crosslinking of the copolymer insitu such as with the use of condensation resins, and multivalent metal salts (e.g. Al3+, Cr3+, Fe3+, Zr4+, and Sn4+) including complexed types. Phosphonate groups can provide, in addition to reactive sites, additional adhesive forces at the interface between the copolymer and the solid surfaces. Phosphonate/phosphonic acid comonomer can be incorporated in the copolymer in an advantageous range of from 0.5% to 40% by weight, and preferably from 1% to 10% by weight.
The copolymers can optionally have incorporated therein a minor amount from 0.5% to 20% of a cationic functional comonomer. Typical cationic monomers contain a quaternary ammonium group. Preferred cationic comonomers are di-C1-C4 alkyl diallyl ammonium chloride, such as diallyl dimethyl ammonium chloride (DADMAC).
In one preferred embodiment a crosslinked copolymer contains incorporated randomly (A)-(E):
(A) from 20% to 75% by weight of comonomer units represented by (1):
wherein Rxe2x80x2 is hydrogen or methyl, ethyl, propyl or butyl, and Rxe2x80x3 and Rxe2x80x2xe2x80x3 are independently hydrogen, methyl, ethyl or propyl;
(B) 20% to 50% by weight of the comonomer represented by (2):
wherein R1 is hydrogen or methyl and R2 is a partial ammonium salt of a sulfo, sulfophenyl, or sulfoalkyl group, wherein said sulfoalkyl group contains a C2-C10 alkylene group or an alkyl benzyl groups containing C7-C16 carbon atoms,
(C) from 0.01 to 2% by weight of a copolymerized ethylenic unsaturated multifunctional comonomer;
(D) from 2 to 40% by weight of a comonomer having the structure (3)
wherein R3 is hydrogen, methyl, or ethyl, R4 is hydrogen, methyl or ethyl, R5 is hydrogen, methyl, or ethyl; and optionally R4 and R5 form a cyclic amide; and
(E) from 0.5 to 40%, more preferably 1 to 40%, by weight of a comonomer according to (4)
wherein X is hydrogen or a monovalent or divalent cation, or mixture of cations selected from the group consisting of Na+, K+, NH4 +, Mg2+, and Ca2+.
The crosslinked copolymers according to the invention are advantageously produced in a (1) dilute, agitated, aqueous solution polymerization (see Example 1). Other polymerization techniques that are well known to those skilled in the art that can be used with some pre- and post-polymerization adaptation are (2) suspension, (3) W/O emulsion, (4) precipitation and (5) gel polymerization methods. Adaptations in the relative amounts and types of initiator and crosslinking comonomer can be made to arrive at the crosslinked copolymers having the specified K-value according to the invention.
Aqueous agitated solution polymerization is illustrated hereinbelow.
The precipitation polymerization method (4) provides copolymerization in organic solvents that can be mixed with water. In this case, the copolymer is directly produced in solid form and can be isolated by removing the solvent and drying. Water-soluble (lower) alkanols, that is, those with 1 to 4 carbon atoms, such as methanol, ethanol, propanol, isopropanol, n-, sec- and iso-butanol, but preferably tert-butanol, can be considered as water-miscible organic solvents that are suitable solvents.
The water content of the lower alkanols used as solvents here should not exceed 5% by weight, otherwise clumping can occur during polymerization. The water content will preferably be not more than 3% by weight. The amount of solvent to use will be governed to a certain extent by the nature of the comonomers used. Generally 200 to 2000 g of solvent will be used per 100 g of total monomers. Aqueous non-gelled solutions containing the copolymer within the specified K-value range can be prepared by dissolving the copolymer in water, optionally warm and/or saline, agitating the solution until a homogeneous and continuous, pumpable solution is obtained. Typical aqueous copolymer weight percent concentrations range from 0.01% to 20%.
Polymerization by way of W/O emulsion (3) provides a water-in-oil emulsion in which aqueous monomer solution is emulsified in an organic solvent that is not miscible with water, such as cyclohexane, toluene, xylene, heptane, or high-boiling gasoline fractions with the addition of 0.5 to 8% by weight, preferably 1 to 4% by weight, of known W/O type emulsifying agents and then polymerized with conventional radical-forming initiators listed below. In this process, water-soluble monomer mixture and internal crosslinking comonomer are copolymerized in the hot state into copolymers having the specified K-value by first emulsifying the monomers or aqueous solutions thereof; water-in-oil emulsifiers being added in an organic solvent not miscible with water that forms the continuous phase, and this emulsion is heated in the presence of radical initiators. The comonomers to be used can be emulsified as such in the organic, water immiscible solvent, or they can be used in the form of an aqueous solution containing between 95 and 5% by weight of comonomers and up to 95% by weight of water, the composition of the aqueous solution depending on the solubility of the comonomers in water and the polymerization temperature to be used. The ratio between water and the monomer phase can be varied within a wide range and is generally 70:30 to 30:70.
To emulsify the monomer phase in the water immiscible organic solvent into a water-in-oil emulsion, 0.10 to 10% by weight (relative to the oil phase) of a water-in-oil emulsifier is added to the mixtures. Preference will be given to emulsifiers having a relatively low hydrophilic-lipophilic balance value. In principle, any inert, water insoluble liquid, that is, any hydrophobic organic solvent, can be used as the oil phase. Generally, use is made of hydrocarbons having a boiling point between 120 and 350xc2x0 C. These hydrocarbons can be saturated, linear or branched paraffin hydrocarbons, or aromatic hydrocarbons such as toluene or xlyene.
Copolymers according to the invention can be obtained by carrying out the polymerization in the so-called xe2x80x9cgel polymerization processxe2x80x9d (6), with adaptations to provide the homogeneous, continuous aqueous solution at the desired concentration levels. This typically involves polymerization of 10% to 60% monomer active aqueous solutions of the comonomers with suitable conventional catalysts without mechanical mixing (agitation), making use of the Trommsdorf-Norrisch effect. Copolymerizable comonomer can be batch- charged along with the principal comonomers, yielding a uniform, random crosslinked copolymer structure, or a post-polymerization crosslinking method can be used in which crosslinking monomer is applied to a mass of copolymer in a carrier medium.
It is critical that crosslinking comonomers utilized in the preparation of the crosslinked water-soluble copolymer according to the invention are monomers which are uniformly and randomly copolymerized, or uniformly graft-linkable into the copolymer, Crosslinking comonomers react with a radical or abstractable hydrogen at more than one site in or between polymer chains. Bonding sites can be intramolecular (branching) and intermolecular, linking chains together by covalent bonds or crosslink at the incorporation point. There is a low degree of intermolecular networking, below the level recognizable by the skilled person in light of this description, which gives rise to a poorly pumpable gel. The crosslinked copolymers herein forming a stable, non-gelled solution as a result of obtaining a molecular size or weight, as characterized by the herein mentioned K-value test, of from 220 to 450. Below and above this range, less than desired developed solution RPM properties and lack of substrate perfusion, respectively, are typically experienced.
Examples of useful multifunctional crosslinking monomers include multifunctional acrylamides, and (meth)acrylates containing unsaturation at preferably 2, and optionally 3 or more sites on each copolymerizable comonomer molecule. In one embodiment, the multifunctional crosslinking monomers are selected from the group consisting of monomeric polyesters of acrylic or methacrylic acids and polyhydric alcohols; and monomeric polyalkenyl polyethers of polyhydric alcohols containing from 2 to about 6 polymerizable alkenyl ether groups per polyether molecule. Another exemplary crosslinking monomer is a monomeric polyester of an acrylic or methacrylic acid and a polyhydric alcohol containing from 2 to about 6 polymerizable xcex1,xcex2-unsaturated acrylic groups per polyester molecule. Other copolymerizable crosslinking monomers include divinyl ether, ethylene glycol dimethacrylate, (m)ethylene-bisacrylamide, allylpentaerythritol, and the like. The preferred crosslinking comonomers are somewhat water soluble and monomer soluble.
Specific examples of other crosslinking monomers include trimethylol propane triacrylate (TMPTA), trimethylol propane trimethacrylate (TMPTMA); diethylene glycol diacrylate (DEGDA), diethylene glycol dimethacrylate (DEGDMA), trimethylene glycol diacrylate, butylene glycol diacrylate, methylene-bis-acrylamide, pentamethylene glycol diacrylate, octylene glycol diacrylate, glyceryl diacrylate, glyceryl triacrylate, neopentyl glycol diacrylate, the tetraacrylate ester of pentaerythritol, etc.
It is understood that certain monounsaturated monomers may act in varying degrees to crosslink or branch the water soluble copolymer of the invention. For example, acrylate monomers with abstractable hydrogens, which can function as radical reactive sites, can in some embodiments of this invention, form a more branched or crosslinked polymer, thus affecting the preferred levels of the polyethylenic unsaturated crosslinking comonomers. An example of a monounsaturated monomer with an abstractable hydrogen is 2-ethylhexyl acrylate.
Optional heat-reactive, latent carboxy- or hydroxy-reactive internal crosslinking system can be provided by the incorporation of carboxylic-group containing comonomers, and N-alkylol amides, for example, N-methylol acrylamide, N-propylol acrylamide, N-methylol methacrylamide, N-methylol maleimide, N-methylol maleamic acid esters, N-methylol-p-vinyl benzamide, and the like.
Known methods for optional post-polymerization crosslinking of carboxylic acid containing copolymers include U.S. Pat. No. 4,666,983 (crosslinking agent without any carrier solvent), using e.g. polyhydric alcohols, polyglycidyl ethers, polyfunctional amines and polyfunctional isocyanates. U.S. Pat. No. 4,507,438 and 4,541,871 utilize a difunctional compound in water with inert solvent or mixture of solvents. The difunctional compounds include glycidyl ethers, haloepoxies, aldehydes and isocyanates with ethylene glycol diglycidyl ether crosslinker. The solvents include polyhydric alcohols with ethylene glycol, propylene glycol and glycerine enumerated as preferred polyhydric alcohols. U.S. Pat. No. 5,140,076 teaches a water-solvent-crosslinker mixture. Crosslinkers such as polyhydric alcohol, diglycidyl ether, polyaziridene, urea, amine and ionic crosslinkers are suggested.
The crosslinked, water soluble copolymers are produced in the most preferred manner of a dilute aqueous solution polymerization to yield directly from the polymerization vessel, a non-gelled, dilute, aqueous solution having continuous-flow pumpability in a positive-displacement pump. Alternatively, if the crosslinked copolymer is isolated from the reaction vessel and dried in solid form after elimination of the water in conventional drying processes, it can be redissolved in water after comminution with suitable equipment and then used according to the present invention.
In general, the polymerization reaction is preferably carried out in a temperature range of from 0xc2x0 C. to 150xc2x0 C., preferably 10 xc2x0 C.-125xc2x0 C., more preferably from 20xc2x0, to 110xc2x0 C., and under ambient (standard) or increased pressure. Polymerization is generally carried out in an atmosphere of protective gas, preferably nitrogen. Particular attention to elimination of oxygen is critical.
Polymerization can be initiated by high-energy electromagnetic radiation or conventional chemical initiators. The latter include, but are not limited to, organic peroxides such as benzoperoxide, tert.- butylperoxide, methyl ethyl ketone peroxide, cumene hydroperoxide, azoic compounds, for example, azodiisobutyronitrile or 2,2xe2x80x2-azobis-(2-amidinopropane)-dihydrochloride, as well as inorganic peroxy compounds, for example, (NH4)2S2O8, K2S2O8, or H2O2, perhaps in combination with reducing agents, for example, sodium hydrosulfite and iron-II-sulfate or redox systems, the reducing components being an aliphatic and aromatic sulfinic acid, for example, benzene sulfinic acid and toluene sulfinic acid or derivatives of these acid such as Mannich adducts of sulfinic acid, aldehydes and amino compounds. As a rule, 0.002 to 2 g of the polymerization initiator is used per 100 g of total monomers. If more initiator is used, it may be required to utilize more crosslinker than specified herein above, which will be apparent to skilled practitioners.
It is possible to make an addition to the polymerization recipe, according to the invention, of from about 0.01 to about 2%, on the total weight of the copolymerizable comonomers charged to the reaction zone, so-called moderators which harmonize the course of the reaction in that they flatten the reaction rate-time diagram. They may lead to an improvement in the reproducibility of the reaction and thus make it easier to produce uniform products with reduced K-value variability. Examples of suitable moderators of this type include nitrilo-tris-propionylamide, monoalkylamines, dialkylamines or trialkylamines such as diisbutylamine, for example. Such moderators can also be used to advantage in the production of the copolymers according to the invention, but are not essential in the practice of the invention.
Chain-transfer agents (CTA""s) can also be added to the polymerization recipe before or during polymerization, or in conjunction with the post-polymerization, in-reactor crosslinking. Examples of conventional CTA""s include the alcohols, e.g., methanol, ethanol, propanol, isopropanol, n-butanol, sec. -butanol and amyl alcohols, alkyl mercaptans such as dodecyl mercaptan and amyl alcohols, alkyl mercaptans such as dodecyl mercaptan and tert. dodecyl mercaptan, isooctylthioglycolate and some halogen compounds such as carbon tetrachloride, chloroform and methylene chloride. If chain transfer agent is used, it will be apparent to skilled practitioners to alter the polymerization process by adjusting the initiator type or concentration, temperature of reaction, monomer concentration, and/or amount of crosslinking monomer charged, by routine trial and error to provide a copolymer K-value in the range according to the invention.
The treatment solution of water-soluble, crosslinked copolymer according to the invention can be prepared with tap or deionized water, or proportioned to some extent with salt solution. Optionally at the well-bore site, produced water, which is in the nature of a brine obtained from the drilling site, could be added to the crosslinked copolymer solution. Generally, the treatment solution which is in a form for injecting underground, can be further diluted in water, whether DI, fresh, salt or brine water.

Synthetic crosslinked copolymer solutions and direct injection to subterranean oil and gas formations


An arrangement (1, 1xe2x80x2) for automatically unstacking containers (6, 6xe2x80x2) nested in each other in lying posture, by depositing them on a support, e.g. a conveyor (3a), with the container opening (6a) facing upwards, the arrangement comprising a gripping device (5) for gripping and moving out the respective first container (6) of a lying container stack (2, 2xe2x80x2), the gripping device (5, 5xe2x80x2) being arranged on holding elements (8a, 8b) movable in stacking direction, and further comprising a clamping device (4) for holding back the lying container stack (2, 2xe2x80x2), with the foremost container (6) being left free, wherein the gripping device (5) is provided with lateral pressure-medium cylinders (5a; 46) which have horizontal axes on the same level and which are connected with the holding elements (8a, 8b) extending thereabove.

The invention relates to an arrangement for automatically denesting containers in lying position and nested in each other, the containers being deposited on a support, e.g. a conveyor, with the container opening facing upward, the arrangement comprising gripping means for gripping and moving out a respective first container of a lying container stack, the gripping means being arranged on holding elements movable in the direction of the stack, and further comprising clamping means for holding back the lying container stack, with the foremost container being left free.
Containers which as a rule have frusto-conical shapes, i.e. have oblique walls, are stored in stacks in warehouse stocks or in commissioning systems, e.g., and they must be denested again before use and supplied individually for filling. Denesting should occur rapidly and gently and, in particular, it should be automated since the individual containers are supplied to conveying means in intermittent manner, and manual denesting would be very laborious.
In DE 3 042 903 A, automatic denesting has been described. Here, a lifting mechanism is provided which engages the respective uppermost container of a vertical container stack advanced on a conveyor belt, which lifts this uppermost container and which deposits it on a conveyor belt. What is of disadvantage is that the lifting mechanism is relatively complex in construction, primarily since it must engage containers at ever changing levels; moreover, the vertical container stacks pose problems if they have to be advanced over larger distances since, in case of major stack heights, they have little stability and topple easily if their movement is started or stopped with jerks.
According to U.S. Pat. No. 4,915,578 A, a vertical container stack is top-delivered to a holding device, the lowermost container being left free so that it drops onto a conveyor belt provided therebelow and is moved off by aid of the same. In detail, two oppositely arranged flange rims of the containers lie on projecting tooth ledges of a chain, which tooth ledges guide the containers downwardly in still stacked manner. By means of projections engaging the two oppositely arranged rims of the lowermost container from above, a second chain moving faster and in counter-direction pushes this lowermost container from the stack downwards to below so that it drops to the conveyor belt at last and is transported away. Here, too, it is a disadvantage that the stack is provided vertically, with the risk of tilting, as already described before, primarily in case of major stack heights. Moreover, the devices used must be built high, increasing construction costs. The container stack must not exceed a certain height also because otherwise it would become too heavy and the stack could no longer be carried by the device.
In U.S. Pat. No. 4,983,098 A, an arrangement of the present type is described, for providing cup-shaped conical containers individually before they are filled and closed, the containers being delivered in vertical stacks which are turned over. From the lying container stack, the foremost container is gripped by vertically movable lug members which then are moved horizontally together with the foremost container so as to pull it away from the remaining stack. At the same time, the second container is held back by like, vertically movable lug members. To be put into an upright position, the foremost container moves against a pivotable hook member which grips the upper container rim at its inner side so that the container is decelerated at its upper rim while it is transported on on the conveyor; this results in upright tilting of the container. A disadvantage is that the lug members which engage behind the container rims with one of their legs must be precisely adapted to the containers and that their vertical movement requires a relatively complex driving means which in parts must be mounted laterally of the conveyor.
In U.S. Pat. No. 4,054,212 A, finally, an arrangement for downwardly tilting cup-shaped containers, bottoms first, is described, wherein this denesting should be effected in an automatic drink dispenser. The cups are pushed forwards by pivotable ram arms via arcuate rails until they fall into a holding means on a conveyor. At the same time, the second cup of the stack is kept back by gripping fingers. This construction is provided for denesting cups, and it is hardly suitable for containers of substantially larger mass.
It is an object of the invention to provide an arrangement for denesting, as initially indicated, with which it is possible to denest nested containers in a rapid and reliable manner, by using simple construction measures, as well as with a high flexibility as regards container dimensions.
The arrangement according to the invention of the initially defined kind is characterized in that the gripping means is provided with lateral pressure-medium cylinders which have horizontal axes on the same level and which are connected with the holding elements extending thereabove. Because of the lying posture of the container stack, the structural height of the arrangement can be a low one, and also the containers need not be lifted or need be lifted only slightly. Thus, the xe2x80x9coverheadxe2x80x9d-arrangement of the holding elements does not pose any problems. The use of pressure medium cylinders for the gripping means allows for a simple mode of construction, while nevertheless an easy, reliable and rapid gripping of the foremost container is possible. Since the pressure medium cylinders have horizontal axes on the same level, the foremost container is tightly held between the pressure medium cylinders, with the containers neither tilting nor sliding off-center.
The entire lying or horizontal container stack can be lifted from its support by a lifting mechanism before the foremost container is moved on, the lifting mechanism being capable of reaching between rollers of a roller conveyor provided as support, e.g.; the lifting mechanism may, however, also be built with rails or lifting ledges engaging laterally on the lower side of the container stack, in which case the stack support may also be formed by a conveying belt. Lifting of the container stack reliably prevents frictional sliding of the first container along the support while it is being pulled away from the container stack. Apart from the fact that the containers and the conveyor are carefully treated thereby, in this manner the amount of energy employed is minimized.
The pressure medium cylinders provided according to the invention may engage the respective container frictionally or positively, and suitably they are simply released from the container after the respective container has been moved away from the remaining stack and after it has been pivoted, and thus this container is simply dropped onto its support; the dropping height may be low so that a gentle xe2x80x9cdepositingxe2x80x9d of the containers nevertheless is ensured. The pressure medium cylinders are to be designed such that they are capable of transmitting the respective transverse forces; optionally, also a lever mechanism can be provided. For pivoting of the containers while providing them individually, it is particularly advantageous if the pressure medium cylinders are rotatably arranged on the holding elements.
It is particularly advantageous if the holding elements are mounted to be linearly displaceable in parallel to the container stack. In this manner, the foremost container is linearly moved away from the remaining container stack. The foremost container suitably is gripped at its opening rim or collar facing rearwards, and is pushed from the container stack with its bottom facing forwards, the container bottom of the foremost container at least in the starting phase of pushing from the stack being located at a distance above the support so that the container does not chafe on the support.
The pressure medium cylinders, or their piston rods, respectively, may be oriented coaxially, and may be provided with a rubber head or the like with which they can be pressed softly against the container and safely against slipping aside therefrom. In the case of rotatable pressure medium cylinders, simple pivoting of the foremost container about the horizontal axis of the pressure medium cylinder into a substantially horizontal position is enabled, i.e. with the opening facing upwards, wherein only the pressure medium cylinders carry out a rotational movement and other parts of the gripping means would not have to be rotated.
Moreover, it is advantageous if the holding element, e.g. the legs of a frame, are mounted on a linear guide. In this case, a pressure medium cylinder may press the frame in the direction away from the container stack, and by the frame it is ensured that both sides of the container will be gripped and moved simultaneously, whereby the container will remain exactly straightly aligned and not get stuck by jamming, e.g. because of a slight turning out of this longitudinal alignment on the container stack.
For a simple depositing of the containers, it is particularly advantageous if the support receiving the denested containers is preceded by an edge provided at a higher level relative thereto, for tilting of the individual containers. After the foremost container has been moved out of the container stack as described above, it is moved in lying posture, with the container bottom facing forwards, to the edge, and there it is released for turning by tilting about this edge and for deposit on the support following the edge, e.g. a conveyor. In this case, the container must be pulled away from the next container merely by a short distance, and it can be guided to the edge by means of a conveyor, e.g. a conveyor belt or a roller conveyor. As soon as a sufficiently large part of the container projects beyond this edge, it will tilt, as a consequence of gravity, with the container bottom downwards to the support located at a somewhat lower level, and there it comes to stand upright. From there it will be led away immediately to make room for the next container. The edge will be provided as close to the denesting arrangement proper as possible, so that the individual lying container need not be transported far before it tilts onto the support. In terms of construction it is also possible to make the height difference of these two supports adjustable, e.g. in that the consecutive support is shiftable in terms of height, or in that it is mounted to be pivotable about an axis, wherein, optionally, an ascent or a descent is brought about. In this manner, differently sized containers can be provided individually. To avoid rubbing of the containers along the support, the pressure medium cylinders here preferably are not rotatable, but fixedly mounted on the holding elements, and thus they carry the entire mass of the container.
A further preferred arrangement is characterized by a cam control for the holding elements so as to move the foremost container according to a predetermined, in particular arcuate, movement out of the container stack and deposit it on the support, e.g. the conveyor, by pivoting it into a position with the container opening facing upwards. The amount by which the container is lifted will depend on the depth of the container. In any event, by the pivoting movement, slipping of the container on the support and thus an increased frictional resistance can largely be avoided. The container openings of the containers in the lying container stack may face forwards, whereby pulling out and turning of the respective foremost containers can be realized particularly simply in one single, continuous movement. Yet the containers may also be provided with the container bottom facing forward, in which case pivoting of the container will be caused only after the foremost container has been pulled away from the stack.
As has already been suggested, in the last-mentioned embodiment, it is advantageous for minimizing movement during denesting if the foremost container is moved away from the lying container stack with its opening facing forward. While the foremost container is moved out and upwards, it will tilt automatically into a position with the container opening facing upwards, most simply by the container""s center of gravity being arranged behind or below the point of engagement of the gripping means on the container, whereby the container seeks to assume the lowermost position.
To controlledly pull the foremost container out of the container stack it is also advantageous if the holding elements, e.g. the legs of a frame, are pivotably mounted. In this manner, the various individual movements of the foremost container will be combined and coordinated with each other in a very simple manner: At the same time as the first container is pulled out of the container stack, the axis of the pressure medium cylinders and thus also of the containers is arcuately moved forward and upwards by the pivotal movement of the holding elements, which movement is assisted by the oblique container walls, since in this manner, frictional slipping of the container on the support is prevented; when pivoted further, the container finally assumes its position with the opening facing upwards.
The holding elements may also have an associated connecting-link guide or a four-bar linkage for control of their movement. The movement of the holding elements and, thus, of the containers may be optimized so that merely minimal lifting of each foremost container is effected while it is being pulled away from the stack, without lifting the container for an unnecessary large distance to then lower it immediately thereafter and to put it onto the support.
To efficiently effect the translation or pivotal movement of the holding elements, preferably pressure medium cylinders are provided as drive for the holding elements.
To grip the foremost container particularly tightly, it is advantageous if the gripping means comprises gripping jaws to be pressed against the container, which are attached on pivoting levers engaged by the pressure medium cylinders. The pivoting levers in this case are pivotably mounted, e.g. on brackets fixedly attached on the holding elements. By actuating the pressure medium cylinders, the pivoting levers are pivoted about their pivot axis, and thus the gripping jaws are pressed against the foremost container. Should the foremost container be jammed in the next container, the gripping jaws are further pivoted by the forward movement of the holding elements and pressed more tightly against the foremost container. This increases the pressing effect, and the foremost container will reliably be moved out of the container stack.
To pull the first container out of the container stack, a particularly simple construction becomes possible if the clamping means contains a pressure medium cylinder which presses at least the second container in the stack downwards, preferably in combination with a lifting mechanism which lifts the entire lying container stack.
To ensure a safe positioning and holding back of the container stack, the clamping means may also have an associated stop for the container stack, which stop can be moved out of the way of the containers, e.g. by pivoting. The arriving container stack is stopped by the stop at precisely the correct position for clamping retention. While subsequently the gripping means grips the foremost container, the stop can, quickly be moved out of the way, e.g. by pivoting, so that removal of the foremost container from the container stack will not be impeded thereby. After this container has been removed, the stop can be activated again so as to stop the remaining container stack, which has been moved forward in the correct position regarding the clamping means. It is also possible that one stop is provided on each lontigudinal side of the container stack on the support, e.g. on the conveyor.
Moreover, it is also advantageous if a trigger photoelectric barrier is provided for actuating the pressure medium cylinder and/or the stop. In that case, the trigger photoelectric barrier exactly controls the temporally correct actuation of the pressure medium cylinder and or the stop, respectively, if the container stack is moved forwards in each instance. The trigger photoelectric barrier may, e.g., be provided on the support in the region of the lifting means or laterally on the stand.
It is also advantageous if a monitoring photoelectric barrier is provided for sensing the remaining containers of the stack. With this, the clamping means can be switched off if all the containers of a stack have been provided individually, and/or a further container stack can be requested in time.
Optionally, a vertical container stack may be turned over to the horizontal on a conveyor prior to denesting, so as to provide the container stack in lying posture. In this manner, the containers may previously be stacked to a vertical container stack which, as a rule, is easier than stacking in lying posture. For denesting, suitably already turned, lying container stacks are supplied so that their advancing can be effected without any problems, wherein also several turned container stacks may be slid into one another prior to denesting.
Accordingly, it is suitable if the gripping means is preceded by a pneumatically actuated stack turning device. Thus, stacking of the containers may be effected in vertical state and denesting them in lying state. By the pneumatic actuation, simple control and reliable functioning of the stack turning device is achieved.
A stack turning device of advantageous function is obtained if it comprises a stack sliding support which is vertical in the resting position and is pivotable about a horizontal axle. The vertically upright container stack leans against this sliding support. The sliding support is at least as long as the container stack is high so as to support the latter during the turning movement. The sliding support pivots, e.g. by aid of a pressure medium cylinder, about an upper horizontal axis, the lower end moving the lowermost containers of the container stack out of the upright position so that the stack begins to tilt. For a minimum force to be applied, the axle about which the sliding support tilts is provided in the upper region of the sliding support, whereas the pressure medium cylinder driving it engages as low on the sliding support as possible, whereby the lever action is best utilized. The container stack is supported by the sliding support while being turned to a lying posture, the pivot movement of the sliding support being continued such that both the sliding support and the container stack assume an ever more slanted position, yet with the lowermost container always remaining in xe2x80x9cbottomxe2x80x9d contact (with the conveyor). As soon as a certain minimum inclination has been attained, the container stack will slide down along the sliding support and thus will come to lie. Such sliding is assisted by a guided movement of the lowermost or foremost container, respectively, on the support, e.g. by the support being a driven conveyor, e.g. a conveyor belt. The latter may immediately transport away the lying container stack so as to make room for the next container stack. The next upright container stack is brought to the turning device by a conveyor so that the stack again abuts on the sliding support which meanwhile has been pivoted back into its starting position.
A particularly advantageous construction provides that a roller is provided opposite the sliding support on a stand, which roller forms a stack stop when turning the stack into the horizontal position. This roller may be mounted on a transverse beam of the stand so that the upper stack region abuts on the roller and is held back by the latter while the sliding support carries out its pivotal movement. Also several rollers mounted on the stand in spaced-apart relationship would be conceivable.
A simple, efficient construction is also obtained if the stack turning device comprises angled forked arms mounted so as to be pivotable about their horizontal angle axis. In that instance thexe2x80x94verticalxe2x80x94container stack is pushed onto the one fork arms until it comes to abut on the upright second fork arms provided approximately at right angles to the former. The upright fork arms subsequently are pivoted into the horizontal, thereby acting as support for the stack which simultaneously is held by the other, originally horizontal fork arms, which are tilted up into a vertical position, so that in doing so, the stack is always kept and manipulated under control.
A particularly preferred construction is characterized in that the stack turning device comprises supporting devices for the container stack, which are movable relative to each other and which have associated separate pressure medium cylinders for their independent pivotal movement. These supporting devices may, e.g., be two pairs of fork arms which are pivotable upwards and downwards independently of each other about a mutual horizontal axis or about separate horizontal axes of their own, in the region of the support, i.e. the conveyor.
For a continuous operation of the automatic denesting, a container rotating device for rotating the denested box-type containers from their transverse orientation into a longitudinal orientation is advantageous. In this manner, the containers are automatically moved on in the longitudinal orientation usually desired in commissioning systems, e.g., and this even if the containers are obtained in transverse orientation after denesting, which frequently will be the case since with lying stacks, for reasons of stability the containers will arrive with their larger side face lying on the conveyor.
For use in commissioning systems, it is also advantageous if the container rotating device has an associated control unit for rotating each container with a pre-determined side facing forward. In commissioning systems, in most instances the front walls of the containers carry documents, codes etc. which are important for the controlled movement of the container through the commissioning system and for its filling. In that instance, reading units are provided in the commissioning system for the proper function of which the correct orientation of the containers is important.
A particularly simple construction of the rotating device consists in that it comprises two stops, e.g. cylinders, adjacently arranged on the conveyor provided as the support and selectively projectable across the conveying plane, after which the conveyor preferably narrows. Depending on the direction in which the container is to be rotated, one or the other cylinder lowers so that it no longer projects from the conveying plane. The container which has been advanced is stopped on one of its sides by the one projecting cylinder, while the other side of the container is moved on by the conveyor. This results in a rotation of the container about the protruding cylinder, past which it is guided. The guides on both sides of the conveyor narrow in transporting direction until the distance between them allows only the passage of a longitudinally oriented container. In this narrowed portion, the container which has already been rotated to some extent is forced to a complete longitudinal orientation.
As has already been mentioned, according to the present invention stacks of differently high containers can be denested without any problems. For the differently high containers subsequently being specifically usable for their respective tasks, they have to be distributed according to their heights. Accordingly, preferably a shunting means is provided for distributing the individually provided box-type containers to various conveying paths, e.g. in accordance with their container height. In most instances, two consecutive conveyors will be present, at least one pivotable lever or pivot arm in each case merely leaving the desired consecutive conveyor accessible by which the container is to be conveyed, and blocking access to the other consecutive conveyor.
For a simple recognition of the container height of the container which has just arrived, it is advantageous if the shunting means has a preceding container height sensor, e.g. with photoelectric barriers at different levels. If a container of a certain height is moved past the sensor, the latter senses this and transmits a signal corresponding to the sensed container height, for pivoting the lever or pivot arm into a certain position.