SYSTEMS AND METHODS FOR PREPARATION AND ADMINISTRATION OF GELS.
Patent Information
- Application Number
- MX2021000352
- Authority / Receiving Office
- MX · MX
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2018-07-10
- Filing Date
- 2021-01-08
- Publication Date
- 2026-02-25
- Estimated Expiration
- 2039-07-10
AI Technical Summary
Existing gel-based applications face challenges in uniform mixing of active ingredients due to high viscosity, which complicates delivery methods such as spraying, and high-pressure requirements, especially in high-throughput animal production facilities like hatcheries, where vaccines need to be evenly mixed and administered.
A two-component gel system comprising low-viscosity aqueous solutions that form a gel upon mixing, allowing for easy mixing and low-pressure administration, including a binder/crosslinking agent and a gelling component, which can encapsulate oocysts or sporocysts to prevent dehydration.
The system facilitates uniform mixing and low-pressure delivery of vaccines, maintaining the integrity of oocysts or sporocysts, enhancing vaccine efficacy by prolonging their viability and ensuring consistent administration in high-throughput settings.
Abstract
Description
SYSTEMS AND METHODS FOR PREPARATION AND ADMINISTRATION OF GELS CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application 62 / 696,261 filed on July 10, 2018, Hutchins et al., which is incorporated herein in its entirety by reference. This application is related to pending PCT application No. PCT / US19 / 41178, filed on July 10, 2019, James Hutchins et al. This co-pending PCT application is incorporated herein in its entirety by reference. FIELD OF INVENTION This description provides systems and methods for forming a gel on a surface. In one embodiment, the system may have a first container with a first low-viscosity aqueous solution comprising a binder / crosslinking agent; and a second container with a second low-viscosity aqueous solution comprising a gelling component. The first and second separate solutions are sprayed or otherwise applied onto a surface where the solutions mix to form a gel. In addition to the systems, methods are also provided. In one embodiment, at least one of the low-viscosity aqueous solutions contains an administerable product of interest, such as a vaccine. BACKGROUND OF THE INVENTION Introduction The "background" description provided herein is intended to present the general context of the description. The work of the inventors currently named, to the extent described in this background section, as well as aspects of the description that otherwise cannot qualify as prior art at the time of filing, are not admitted either expressly or implicitly as prior art against the present description. Gels offer the benefit of formulations that adhere to a surface and remain where applied. A gel will keep a product of interest localized to a particular area. Therefore, many medications, preventive treatments, and therapies are formulated as gels. For example, a gel for the topical administration of an anesthetic, such as lidocaine, will keep the active ingredient localized to a desired area of interest and away from other areas. Water-soluble gels also have the advantage of hydrating products that can degrade if they dry out. Typically, biological products and vaccines will become inactivated or ineffective when they dry out. It can be difficult to mix an active ingredient uniformly into a gel. Most gel-based applications are manufactured as a gel at production facilities to final concentrations, using automated mixing equipment to ensure uniform dispersion of the active ingredients within the gel. Alternatively, some gels can become less viscous when heated, which aids mixing, but many products are not compatible with higher temperatures. Furthermore, administering gels can be challenging due to their high viscosity, which complicates some delivery methods such as spraying and requires high pressures. Therefore, improved methods are needed for administering gels or gel formulations containing active ingredients. In animal production facilities, such as hatcheries, high-throughput requirements necessitate the processing of hundreds of thousands, a million, or more subjects each day. These processes may include vaccination. In poultry production facilities, these vaccines are concentrates that require dilution before use. Vaccines are typically prepared in 5- to 10-liter batches. Several batches are needed throughout the day. For some vaccines, gel dilution is preferred for administration. Effectively mixing small vials of concentrated vaccine uniformly into large volumes of viscous gel is challenging. It is easier to mix vaccine vials in a low-viscosity aqueous solution. High-viscosity solutions are also difficult to dispense uniformly due to the high pressures required. Vaccines, Apicomplexa, Eimeria and Coccidiosis Vaccines are an important component in protecting humans and animals from pathogenic microorganisms, including viruses, bacteria, and parasites. In short, a vaccine stimulates the immune system to recognize a specific pathogen, thus creating a defense system that protects against future encounters with that microorganism in nature. Vaccines can be divided into several main classes, specifically: inactivated or killed vaccines, subunit vaccines, wild-type vaccines, and live-attenuated or modified live vaccines. Wild-type and live-attenuated vaccines give the recipient animal a mild infection. This mild infection often produces an immune response that prevents a more severe, and potentially fatal, infection from occurring in the future. Apicomplexa is a phylum of single-celled, spore-forming parasites with a complex life cycle. Well-known human diseases caused by apicomplexans include babesiosis (Babesia), cryptosporidiosis (Cryptosporidium parvum), malaria (Plasmodium), and toxoplasmosis (Toxoplasma gondii). Apicomplexan diseases also affect animals and livestock. Some, such as Cryptosporidium parvum and Toxoplasma gondii, affect both humans and animals. Other apicomplexans, such as Eimeria and Theileria, affect only animals. The apicomplexan life cycle is complicated because it has both sexual and asexual reproductive stages. The life cycle often consists of a stage in which the parasite is excreted into the environment and other stages that occur within the host animal. For many apicomplexans, some life cycle stages take place in one host species and other stages take place in another host species. On the other hand, the apicomplexan parasite Eimeria is generally host-specific and monoxenous, meaning its life cycle is specific to a single host species. Sporocysts, a vital stage of Eimeria contained within oocysts, can be released prior to administration to enhance vaccine infectivity. Eimeria causes coccidiosis in wild and domesticated vertebrates, such as cattle, chickens, fish, goats, pigs, rabbits, reptiles, sheep, and turkeys. Different Eimeria species have a preferred section of the gastrointestinal tract (G1) where they reproduce and damage the epithelium of the G1 tract. Coccidiosis is a common disease in poultry. Control of coccidiosis has typically been achieved using ionophores or chemicals in feed. Alternative control measures are currently being sought due to the costs of ionophores and chemicals, consumer demand, and the risk of developing resistant organisms, such as coccidia and others. Coccidiosis vaccines have the potential to drastically reduce or eliminate the need for ionophores or chemicals in feed for coccidiosis control. However, vaccines are not widely used, partly due to a lack of uniformity in mass vaccination. As currently administered, Eimeria vaccines in poultry result in ineffective first-round infectivity and immunity, and generally produce a large population with no prior exposure that is susceptible to the disease.The population without prior exposure subsequently relies on recycling within the rearing farms to induce immunity. The production of infected birds in the first round results in a massive infection of the population with no residual prior exposure. Resolution of the lack of exposure leads to high oocyst production in the period following the first-round infection, resulting in susceptibility to secondary bacterial infections, such as necrotic enteritis, which require antibiotics for resolution. Effective vaccination of all birds on the day of hatching would prevent the morbidity, mortality, and lack of weight gain associated with Eimeria infection. See PCT publication WO 2017 / 083663AI, Karimpour. Currently, the global impact of coccidiosis due to poor performance, morbidity, and mortality is estimated at $300 million. In addition, approximately $90 million is spent in the US.and $3 billion globally for coccidiosis control annually (5m Editor, 2013, High Cost of Coccidiosis in Broilers, The Poultry Site, https: / / thepou|tr / sjtg.corn / news / 2Q1^. BRIEF DESCRIPTION OF THE INVENTION Instead of mixing active ingredients into a preformed gel, a two-component gel system is proposed. This system consists of two low-viscosity aqueous solutions that form a gel upon combination. The advantages of this system are ease of mixing, low-pressure administration, and prevention of dehydration during administration. One embodiment is directed to a system for administering a product of interest. The system includes a first container holding the product of interest in a first solution, a second container holding a second solution, a delivery device in fluid communication with the first and second containers, and an outlet from the delivery device. The first solution moves from the first container to the outlet of the first delivery device to create a first spray. The second solution moves from the second container to the outlet of the second delivery device to create a second spray. Upon administration, the first and second solutions mix to form a gel containing the product of interest. A second embodiment is directed to a system for administering a vaccine solution, containing oocysts, to an animal.The system includes a first container holding intact oocysts in a first solution, a second container holding a second solution, a delivery device in fluid communication with the first and second containers, and an outlet from the delivery device. The first solution flows from the first container to the outlet of the first delivery device to create a first spray. The second solution flows from the second container to the outlet of the second delivery device to create a second spray. Upon delivery, the first and second solutions react to form a gel containing the oocyst solution. Another embodiment targets a system for rupturing the outer membrane of an oocyst, releasing at least some intact sporocysts, and subsequently delivering the resulting mixture to an animal. See pending PCT application No. PCT / US19 / 41178, filed July 10, 2019, by James Hutchins et al. The system includes a first container holding intact oocysts in a first solution, a processing chamber, and a first delivery device having a first delivery outlet. The system also includes a second container holding a second solution and a second delivery device having a second delivery outlet. The first solution moves from the first container to the processing chamber, where at least some of the oocyst membranes rupture, creating a first solution that is a mixture of oocysts and sporocysts.The first solution is transferred to the first delivery outlet to create a first spray, and the second solution is transferred from the second container to the second delivery outlet to create a second spray. The first and second solutions mix after administration to form a gel containing oocysts and sporocysts. Formulations used for administering oocyst-based vaccines can be aqueous solutions or more complex solutions, including gels. Simple aqueous solutions generally do not provide components to prevent oocysts from drying out after spray application. Gel formulations can prevent oocysts from drying out; however, it is difficult to uniformly mix a vaccine into a high-viscosity gel, and similarly, it can be difficult to dispense the high-viscosity product into containers. Processing oocysts to release sporocysts can improve vaccine efficacy; however, since the sporocysts are no longer encapsulated within their natural protective carrier, the oocyst wall, it is important to provide a protective environment to ensure viability.To form a protective gel for the sporocysts, a two-component spray system can be used, where both components are low-viscosity aqueous solutions as described below. When combined, the components form a protective gel that surrounds the sporocysts. This solution avoids the difficulties associated with mixing the vaccine in a viscous solution or dispensing / spraying a premixed vaccine in a high-viscosity solution (e.g., a gel). A preferred commercial bird to be vaccinated using the method of the invention is a chicken. A preferred composition for administration to a chicken comprises sporocysts, or a mixture of sporocysts and oocysts, of one or more Eimeria species selected from the group consisting of E. tenella, E. acervulina, E. maxima, E. necatrix, E. mitis, E. praecox, E. hagani, E. mivati, and E. brunetti. Another commercially available bird preferred for vaccination using the method of the invention is a turkey. A preferred composition for administration to a turkey comprises sporocysts, or a mixture of sporocysts and oocysts, of one or more Eimeria species selected from the group consisting of E. meleagrimitis, E. adenoeides, E. gallopavonis, E. dispersa, E. meleagridis, E. innocua, and E. subrotunda. BRIEF DESCRIPTION OF THE DRAWINGS Having thus described several modalities of the present description in general terms, reference will now be made to the attached drawings, which are not drawn to scale and do not include all the components of the system. Figure 1 is a schematic drawing of the gel modality (1). Figure 2A is a graphical representation of the life cycle of Eimeria oocysts and vaccines. Figure 2B is a graphical representation of the life cycle of Eimeria oocysts in a chicken. Figure 3 is a schematic drawing of the gel modality (2). Figure 4 is a schematic drawing of the gel modality (3). zccnnn / lz / iz / e / yi DETAILED DESCRIPTION OF THE INVENTION Several aspects of this description will be described more fully below with reference to the accompanying drawings, which illustrate some, but not all, of the aspects described. In fact, this description can be incorporated in many different ways and should not be interpreted as limited to the aspects set forth herein. These variations are provided to make this description comprehensive and complete, and to fully convey the scope of the invention to those skilled in the art. Equal numbers refer to identical elements throughout. In figures, the thickness of certain lines, layers, components, elements, or features may be exaggerated for clarity. All publications, patent applications, patents, and other references mentioned herein are incorporated herein by reference in their entirety. Definitions The terminology used herein is intended to describe only particular modalities and is not intended to limit the scope of the invention. As used herein, the term Eimeria means and includes species of Eimeria that infect chickens, consisting of E. maxima, E. mitis, E. tenella, E. acervulina, E. brunetti, E. necatrix, E. praecox, E. hagani, E. mivati, and any combination thereof. Eimeria includes species that infect turkeys, such as E. meleagrimitis, E. adenoeides, E. gallopavonis, E. dispersa, E. innocua, E. meleagridis, and E. subrotunda, and any combination thereof. Eimeria also includes species that infect cattle, such as E. zuernii, E. bovis, E. ellipsoidalis, and any combination thereof. Eimeria also includes E. ahsata, E. bakuensis, E. crandallis, E. faurei, E. granulosa, E. intricata, E. marsica, E. ovinoidalis, E. pallida, E. parva, E. weybridgensis, and any combination thereof. Additionally, the term Eimeria includes E. intestinalis, E. vejdovskyi, E. piriformis, E. coecicola, E. irresidua, E. flavescens, E. exigua, E. magna, E.perforans, E. media, E. stiedae, and any combination thereof. The terms “animal” and “animal subjects” include, but are not limited to, mammalian and / or avian subjects. Suitable mammalian subjects include, but are not limited to, primate subjects (e.g., human subjects and non-human primate subjects such as apes), porcine subjects, bovine subjects (e.g., cattle), caprine subjects, equine subjects, feline subjects, ovine subjects, canine subjects, murine subjects (e.g., mouse, rat), and lagomorph subjects. As used herein, the terms “birds” and “avian subjects” (i.e., “subjects that are birds”) are intended to include males and females of any avian species, but are primarily intended to encompass poultry that are commercially reared for eggs or meat, or as pets. Accordingly, the terms “bird” and “avian subject” are intended particularly to include, but are not limited to, chickens, turkeys, ducks, geese, quail, pheasant, budgerigars, parrots, cockatoos, cockatiels, ostriches, emus, and the like. In particular instances, the avian subject is a chicken or a turkey. As used herein, the term “low viscosity” is defined as approximately 1 centipoise at 20 degrees Celsius. As used herein, the term “grooming” is defined as the act of a chicken or other animal ingesting oocysts or other materials by grooming itself or another animal, and subsequently consuming the groomed material to initiate infection. As used herein, the term “acceptance”, “acceptance percentage”, or “% acceptance”, in the context of vaccine infectivity, is defined as the subject who has been shown to be positive for an apicomplexan infection, including, but not limited to, Eimeria, after vaccination. As used herein, the singular forms “a,” “an,” “the,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It shall also be understood that the terms “comprises” and / or “comprising,” when used herein, specify the presence of the stated features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more additional features, steps, operations, elements, components, and / or groups thereof. This description may conveniently “comprises,” “consists of,” or “consists essentially of” the steps, elements, and / or reagents described in the claims. It is further noted that claims may be drafted to exclude any optional elements. Thus, this statement is intended to serve as a precedent for the use of exclusive terminology such as “only,” “just,” and the like in connection with the recitation of elements in accordance with the claim, or the use of a “negative” limitation. As used herein, the term “and / or” includes any and all combinations of one or more of the associated enumerated elements. As used herein, phrases such as “between X and Y” and “between approximately X and Y” should be interpreted to include X and Y. As used herein, phrases such as “between approximately X and Y” mean “between approximately X and about Y.” As used herein, phrases such as “from approximately X to Y” mean “from approximately X to approximately Y.” Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by a person skilled in the art to which this invention pertains. Terms, such as those defined in commonly used dictionaries, are to be interpreted as having a meaning consistent with their meaning in the context of the specification and the relevant art, and are not to be interpreted in an idealized or overly formal manner unless expressly defined herein. Known functions or constructions may not be described in detail for the sake of brevity and / or clarity. The sequence of operations (or steps) is not limited to the order presented in the claims or figures unless specifically stated otherwise. Throughout this descriptive report, the terms “around” and / or “approximately” may be used in conjunction with numerical values and / or ranges. The term “approximately” is understood to mean values close to a given value. For example, “approximately 40 [units]” may mean within ±25% of 40 (e.g., 30 to 50), within ±20%, ±15%, ±10%, ±9%, ±8%, ±7%, ±6%, ±5%, ±4%, ±3%, ±2%, ±1%, less than ±1%, or any other value or range of values at or below that value or range. Alternatively, depending on the context, the term “approximately” may mean ± half a standard deviation, ± one standard deviation, or ± two standard deviations. Furthermore, the phrases “less than approximately [a value]” or “greater than approximately [a value]” should be understood in light of the definition of the term “approximately” provided herein. The terms “around” and “approximately” may be used interchangeably. Throughout this specification, numerical ranges are provided for certain quantities. It should be understood that these ranges encompass all their subranges. Therefore, the range “50 to 80” includes all possible subranges within it (e.g., 51–79, 52–78, 53–77, 54–76, 55–75, 60–70, etc.). Furthermore, all values within a given range can be endpoints of that range (e.g., the range 50–80 includes ranges with endpoints such as 55–80, 50–75, etc.). Unless otherwise defined, all technical and scientific terms used herein have the same meanings commonly understood by a person skilled in the art to which this description pertains. Preferred methods, devices, and materials are described, although any method and material similar to or equivalent to those described herein may be used in the practice or testing of this description. All references cited herein are incorporated in full by way of reference. Two-component gel modalities The embodiments described below are directed to a two-part gel system. One embodiment utilizes a two-component system in which neither component is initially a gel, but when combined, they form a gel. In a first gel embodiment, a system may consist of a first component comprising a gelling agent in a low-viscosity aqueous solution, such as a sodium alginate solution, and a second component that is a low-viscosity aqueous solution containing a binder / crosslinker, such as a liquid calcium chloride solution. Each spray component is a relatively low-viscosity aqueous solution compared to a gel, facilitating mixing and spraying. When the low-viscosity aqueous solutions are sprayed, or otherwise applied, onto a surface of interest and allowed to combine, a gel is formed.The newly formed gel can protect the substance from the environment, increasing the time the gel remains on the surface it was sprayed onto. It is understood that the two-component gel system can have many applications, including, but not limited to, the food, agricultural, military, aerospace, chemical, biochemical, pharmaceutical, nutraceutical, cosmetic, printing and manufacturing industries, and any other application where a gel coating or gel application can be used. Examples of uses for a two-part gel system include herbicide and pesticide applications, paint, and other coating applications. Another anticipated application is a dermatological pharmaceutical preparation applied in a two-stage process, where a first solution contains a first active ingredient and a second solution contains a second active ingredient. The first solution is applied to the skin, followed by the second solution. When mixed, the first and second solutions form a gel, but they also form a complete dermatological preparation when the first and second active ingredients are combined. First type of gel The first embodiment of gel 100, shown in Figure 1, includes a first reservoir 12 containing a binding / crosslinking agent in solution 102, which may be a calcium chloride solution, and an outlet 18. The first embodiment of gel 100 also includes a pump (not shown). The first embodiment of gel 100 also includes a first delivery device 46 in the form of a sprayer having a first nozzle 50. The first embodiment of gel 100 further includes a second reservoir 86 containing a gelling agent solution 90. In one embodiment, this may be a sodium alginate solution. The first embodiment of gel 100 also includes a second delivery device 47 in the form of a sprayer having a second nozzle 51. The second reservoir 86 is connected to the second delivery device 47 by means of a second reservoir outlet 88. In use, the binding / crosslinking agent in solution 102 is pumped from the first reservoir 12 to the first nozzle 50. The gelling component solution 90 is pumped from the second reservoir 86 to the second nozzle 51. Both solutions 102 and 90 are dispensed from the first and second nozzles 50 and 51 onto a surface 61. In this way, the binding / crosslinking solution 102 mixes after dispensing with the gelling component solution 90 on the solid surface 61 to form a gel. The two sprays can be dispensed sequentially or simultaneously. A person skilled in the technique would recognize that in an alternative embodiment, the first reservoir 12 can contain the gelling component solution and the second reservoir 86 can contain the binder / crosslinking solution. In this alternative embodiment, when both solutions are sprayed onto a surface 61, they will form a gel at a common location. As can be understood, this first modality 100 is applicable anywhere an aqueous coating is used. As mentioned previously, this includes applications in the food, agricultural, manufacturing, chemical, biochemical, military, aerospace, nutraceutical, cosmetic, printing, and pharmaceutical industries. It is anticipated that the two-part solution described herein may have advantages where one or more of the solution's ingredients may be reactive with another ingredient. By applying the gel in a two-part solution, any reactivity can be avoided until the solution has been mixed into a gel. Second type of gel Parts of the life cycle of an Eimeria oocyst, whether wild-type or attenuated, are illustrated in Figure 2A and Figure 2B. Figure 2A shows an overview of the external process that occurs with the uptake of Eimeria oocysts in chickens. The day-of-hatch chick is first inoculated with a vaccine containing sporulated oocysts (A). The sporulated oocyst is then processed within the chicken's digestive tract. This process is shown in more detail in Figure 2B. Infection continues through multiple life stages, eventually causing the formation of unsporulated oocysts that are excreted in the chicken's feces (B). After excretion by the bird, the unsporulated oocysts are exposed to the heat, moisture, and oxygen of the environment and sporulate over the course of several days (C). The oocysts are not infectious until they sporulate. These sporulated oocysts are then ingested by the chicken and the cycle repeats. Figure 2B shows a magnified view of the internal processes that occur with the uptake of Eimeria oocysts in chickens. The inset region shows a simplified description of the oocyst's reproductive life cycle, in which the membrane of the sporulated oocyst, containing four sporocysts, ruptures, releasing sporocysts (D). Within each sporocyst are two sporozoites. Enzymatic reactions within the avian intestines digest the end of the sporocyst wall (not shown), releasing the sporozoites. The motile sporozoites then seek out and infect intestinal cells (E) in different regions of the intestine in a species-specific manner. For example, in chickens, E. acervulina infects the upper intestine, E. maxima infects the small intestine, and E. tenella infects the cecum. zccnnn / ίζηζ / Β / γι After intestinal cells are infected by sporozoites, the parasite's life cycle continues through several stages of asexual reproduction. These cycles consist of multiple rounds of reproduction and amplification, resulting in a massive increase in the presence of Eimeria within its selected regions of the intestinal tract. Following the amplification caused by the asexual reproduction stages, sexual reproduction occurs, resulting in the production of oocysts, which are then shed in the feces of one chicken and consumed by another, as shown in Figure 2A. The entire process takes approximately 7 days, with exact timeframes varying depending on the Eimeria species. Excystation and subsequent invasion of a host cell occur between day 0 and day 3. Asexual reproduction occurs between day 3 and day 5. Sexual reproduction and subsequent oocyst shedding in feces occur between day 5 and day 7. In commercial poultry operations, mass vaccination may not optimize vaccination frequency, as many birds are either not vaccinated or only partially vaccinated. Mass vaccination is commonly used due to the need for high throughput and the lack of alternative vaccination methods. A novel, high-throughput, individual vaccination method administered directly to a target area can dramatically improve vaccination rates. See PCT publication WO 2017 / 083663AI, Karimpour. When oocysts or sporocysts are sprayed directly into an orifice leading to the digestive tract, such as the eyes, mouth, or nostrils, they are likely to be ingested and processed to the infectious sporozoite life stage.Oocysts or sporocysts sprayed onto feathers may have a limited viability period because live oocysts and sporocysts will dehydrate and die quickly if not kept in an aqueous environment. Viability can be extended if the oocysts and / or sporocysts are encased in a gel to limit dehydration. However, spraying a gel is problematic due to its high viscosity, as is mixing a vaccine evenly into a gel. The second embodiment of gel 110, shown in Figure 3, includes a first reservoir 12 containing an oocyst vaccine solution 82 containing oocysts suspended in a calcium chloride solution. The second embodiment of gel 110 also includes a pump (not shown). The second embodiment of gel 110 also includes a first delivery device 46 in the form of a sprayer having a first nozzle 50. The first reservoir 12 is connected to the first delivery device 46 by means of a first outlet 18 of the reservoir. The second gel modality 110 further includes a second reservoir 86 containing a sodium alginate solution 90 and a second delivery device 47 in the form of a sprayer having a second nozzle 51. The second reservoir 86 is connected to the second delivery device 47 by means of a second reservoir outlet 88. In use, the calcium chloride solution 82 containing oocysts is pumped from the first reservoir 12 to the first nozzle 50. The sodium alginate solution 90 is pumped from the second reservoir 86 to the second nozzle 51. Both solutions 82, 90 are administered simultaneously from the first and second nozzles 50, 51 to the facial mucosa of a day-old pup for direct ingestion, or to another region of the body for grooming. In this way, the oocyst calcium chloride solution 82 mixes after administration with the sodium alginate solution 90 to form a gel 62. The gel 62 is ingested by the pup after the administration of solutions 82, 90 onto the animal's surface or during grooming. The oocysts suspended in the gel 62 prevent dehydration for a longer period of time, giving the brood more opportunities to ingest the gel and thus the oocysts while grooming. It is understood that the calcium chloride or sodium alginate solution can be mixed with the oocyst-based vaccine. Furthermore, solutions 82 and 90 can be sprayed independently, in any order, or simultaneously to achieve the same result, i.e., to form a gel-based mixture. Additionally, the first reservoir 12 can contain the sodium alginate solution, and the second reservoir 86 can contain the calcium chloride solution. The oocysts can be present in either of the two components of the gel-forming system. A preferred formulation includes 2% sodium alginate with calcium chloride at between 3 and 4%, more preferably between 3.5 and 3.8%, to ensure rapid gel formation with sufficient viscosity to maintain encapsulation of oocysts or sporocysts during grooming. Propylene glycol alginate (PGA) can be used as a substitute for sodium alginate. Another alternative formulation to sodium alginate and calcium chloride involves forming a calcium pectate gel by combining a calcium lactate or calcium gluconate solution with an appropriate pectin-containing solution, such as low-methoxyl pectin (LM) or amidated low-methoxyl pectin (LMA). Third type of gel A third gel modality 120, shown in Figure 4, involves the two-component solution described above for the first gel modality 100 and the second gel modality 110. However, the third gel modality 120 incorporates the use of a processing system 24 to rupture at least some of the oocyst membranes, thereby releasing at least some of the sporocysts into one of the two solutions and subsequently administering the solutions as sprays that form a gel when the two solutions are combined. The third gel modality 120 includes a first reservoir 12 containing an oocyst vaccine solution 82 containing oocysts suspended in calcium chloride. The third gel modality 120 also includes a pump 20. A pump outlet 22 is attached between the pump 20 and a processing system 24. The third modality of gel 120 includes a processing system 24 comprising a homogenizer 32. A first nozzle 50 is connected to the processing system 24. The third modality of gel 120 further includes a third reservoir 86 containing a sodium alginate solution 90. The third modality of gel 120 also includes a second delivery device 47, which is a sprayer having a second nozzle 51. The second nozzle 51 is connected to the third reservoir 86. Both the first and second delivery devices 46, 47 are connected to a pressurized air source, not shown. The inlet for homogenizer 32 is seamlessly connected to the first outlet of tank 18. The outlet of homogenizer 32 is seamlessly connected to a second tank 40, which leads to the first delivery device 46. The outlet of the third tank 86 is seamlessly connected to the second delivery device 47. In use, the oocyst solution 82 is pumped by pump 20 from the first tank 12 through the processing system 24. The homogenizer includes a high-pressure source 26, controlled by a pressure valve 28. The high-pressure homogenizer 32 moves the oocysts in the solution 82 through inlet 36 into vessel 30. The homogenizer 32 moves the solution 82 through the small orifice (not shown), causing at least some of the oocyst membranes to rupture and thus releasing at least some of the sporocysts. The solution moves through outlet 38 via inlet 42 to the second vessel 40. The oocysts, ruptured membranes, and sporocysts in solution with calcium chloride result in a modified solution 85. The modified solution 85 moves directly to the first nozzle 50. In an alternative arrangement, the high-pressure homogenizer 32 can be connected directly to the delivery device 46. In this way, the solution produced by the homogenizer 32 is delivered directly instead of being temporarily stored in the second tank 40. When an animal, particularly a day-old chick, is to be sprayed, the first and second nozzles 50, 51 are opened. The pressurized air in both the first and second nozzles 50, 51 creates respective spray profiles of both solutions 85, 90, which combine on the chick's surface and form a gel. When both solutions 85, 90 mix on the chick, they form a gel 87 containing released oocysts and sporocysts. This gel decreases the rate of dehydration and increases the likelihood of ingestion by the animal through additional grooming. Preferably, solutions 85, 90 are sprayed onto one or more mucosal areas of the chick, specifically the eyes and / or beak. As previously indicated with regard to the second 110 or third 120 gel modality, it is noted that the calcium chloride or sodium alginate solution can be mixed with the oocyst-based vaccine before being pumped through the administration devices. Furthermore, solutions 85 and 90 can be sprayed independently in any order or simultaneously to achieve the same result, namely, to form a gel-based mixture on the surface of the animal subject that has been sprayed. It is further understood that although the third gel modality 120 has been described with the homogenizer 32 as processing system 24, it is anticipated that other processing systems may be substituted to obtain the modified solution 85 from the third gel modality 120. It is also understood that while the third gel modality 120 described above implied that solutions 85 and 90 were moved directly from processing system 24 and the third reservoir 86 respectively, it is understood that one or both solutions 85 and 90 could first be moved to a temporary holding tank prior to administration, as shown and described in Figure 4. See PCT Application No. PCT / US19 / 41178, filed July 10, 2019, by James Hutchins et al., for additional processing systems. It should also be noted that all the methods described herein can be applied to an individual animal or to a group of animals. It is understood that the methods described herein can be applied to a large group of young animals or other animals, contained in a box or other container and subject to the administration of a gel-form solution, as described in the gel method (1), (2), or (3). The systems and methods described herein can be adapted for use in aquaculture. Gel beads containing nutrients, medications, or vaccines can be produced on-site and introduced into fish tanks or open water containing farmed fish. Examples of Eimeria species that infect fish include, but are not limited to, E. aurati, E. baueri, E. lepidosirenis, E. leucisci, E. rutili, and E. vanas. Shearing processes can be applied to these species, where applicable, to facilitate the release of more infectious life stages for vaccination purposes. A vaccine against Eimeria that infects fish can be administered via the gel-forming process using gel beads distributed in tanks or open water containing fish. Applications of the two-component gel method The formation of protective gel coatings in situ by combining two low-viscosity components can benefit various applications, such as frost protection for plants or wound dressings for humans or animals. Drones can incorporate vision systems with on-the-fly, two-component gel delivery, specifically and efficiently targeting entire plants or trees, or even individual flowers in an orchard, or injured or wounded animals in a herd. The low viscosity of the individual liquid components would facilitate low-pressure delivery, compared to the high-pressure systems required for direct gel application. The gel system could be used as a frost protection system for plants, administered via small-scale spray bottles or commercially by drones. The system could also be used to deliver medication to individual animals in herds. Vaccines or medications can be administered to herds of livestock species, such as cattle or horses, using drones. The system could potentially be used to deliver medication to humans. Applications could include the treatment of wounds or burns. One advantage of administering a two-component gel for wound or burn treatment would be minimizing contact with and / or abrasion of sensitive tissues. For burn treatment, the two aqueous solutions, each containing an antibiotic or a local anesthetic, are sprayed and form a gel in situ without requiring direct contact with the burn. The following examples further illustrate the description and are not intended to limit its scope. It should be understood that this description is not limited to the particular modalities described, as these may, of course, vary. It should also be understood that the terminology used herein is intended to describe only particular modalities and is not intended to be limiting, as the scope of this description is limited only by the appended claims. EXAMPLES Preliminary investigations on two-component gel While investigating different nozzles for applying the oocyst vaccine to day-old chicks, a method was sought to visualize the spray patterns produced by the nozzles. Initially, water-sensitive paper cards (Syngenta) were used, but the resulting patterns were found to be prone to bouncing, especially near the center of the spray. As an alternative, a method was developed in which a Petri dish was loaded with a 2 ml mixture of 2% sodium alginate. The spray solution incorporated approximately 3% calcium chloride, red food coloring, and, in some cases, an oocyst vaccine. The spray was delivered from the nozzle onto the sodium alginate pool, where a red gel formed upon contact between the two solutions.By analyzing the resulting gel patterns, and especially after visualizing the oocysts contained within the gel under a microscope, the option of using this two-component gel system to administer the vaccine to the bird was developed. The gel forms a protective barrier around the oocysts, potentially allowing them to be available for grooming for a longer period. Both components of the formulation are low-viscosity, which is an advantage over the high-viscosity gel formulations currently used for oocyst vaccine administration. Low-viscosity aqueous solutions offer advantages over current high-viscosity gels, including ease and uniformity of dispersion, and ease of dispensing.In addition to protecting the vaccine components, the gel formulation is expected to reduce rebound and help retain the vaccine or administered substance in the vaccinated subject. Initial experiments administering the vaccine to chicks using the two-component gel method employed 3% calcium chloride and 2% sodium alginate. In some cases, the gel was observed to lose stability after a few minutes on the chicks' feathers. Increasing the calcium chloride concentration from 3% to 5% produced a thicker gel that maintained its structure more uniformly and likely formed a more protective environment for the oocysts or sporocysts. Alginate was dispensed into a Petri dish, and 3%, 4%, or 5% calcium chloride solutions were applied to the alginate drop. The gels formed immediately. However, when the dish was tilted upward, the gel from the 3% calcium chloride combination ran down the dish, while the 4% and 5% calcium chloride gels remained in place. Calcium chloride concentrations of approximately 3.5 to 3.8% are now used. Gel administration of a vaccine Day-of-hat broiler chickens were administered a 1X dose of a coccidiosis vaccine via eye drops (positive control) or ophthalmic spray. The ophthalmic spray was administered using birds held in a static position between two nozzles. The nozzles used an atomizing air configuration. The sprays were directed toward the chicken's eyes. Treatments included a mixture of released sporocysts with residual oocysts, produced by manual agitation with glass beads. For further details, see PCT application No. PCT / US19 / 41178, filed July 10, 2019, by James Hutchins et al. For one treatment, two sets of nozzles were used, with the first set administering a 2% sodium alginate solution and the second set administering the vaccine in a 3.5% calcium chloride solution.The vaccine administered by spray was given in a total volume of 100 µL (50 µL per eye). The vaccine administered by eye drops was given in a total volume of 50 µL (25 µL per eye). An untreated group was also included. After vaccine administration, the birds were placed in cages and reared under standard conditions until day 7. The birds were euthanized, and the intestinal contents of each bird were collected on day 7. Oocysts in the feces were enumerated using the McMaster flotation chamber technique. Infectivity rates are tabulated below. zccnnn / Lznz / Em Table 1. Infectivity rates by species for chickens vaccinated with ophthalmic spray Ophthalmic Spray Treatment Response Frequency (Infected Birds / Vaccinated Birds) Response Amplitude (Average Oocyst Production per Bird) E. maxima E. tenella E. acervulina E. maxima E. tenella E. acervulina No Gel 11 / 14 (79%) 11 / 14 (79%) 12 / 14 (86%) 2.83 x 10⁵ 2.70 x 10⁵ 1.04 x 10⁵ Gel 14 / 15 (93%) 12 / 15 (80%) 15 / 15 (100%) 3.37 x 10⁵ 3.38 x 10⁴ 2.61 x 10⁵ Improvement 14% 1% 14% 1.2 times none 2.5 times zccnnn / Lznz / Em The results indicate improved infectivity with gel treatment, especially for E. maxima and E. acervulina. The results of the positive and negative controls were as expected. Administration of a gel vaccine containing sporocysts In another experiment, the differences between vaccination with sporocysts versus oocysts can be observed. In this experiment, sporocyst release was achieved by hand-agitating a suspension of multi-species oocysts with 4 mm glass beads. This residual sporocyst / oocyst solution and an oocyst-only solution were administered one day after hatching, directed at the facial mucosa. Two sets of nozzles were used, with the first set delivering a 2% sodium alginate solution and the second set delivering the vaccine in a 3.0% calcium chloride solution. When these two solutions come into contact with the bird's surface, a gel forms. It is hypothesized that gel formation keeps the oocyst / sporocyst vaccine hydrated for longer compared to a typical aqueous spray, thus extending the birds' potential preening time.The results of this experiment can be seen in the following table. Table 2: Frequency and amplitude of response for birds subjected to spraying with oocysts or sporocysts with residual oocysts in a gel Gel spray treatment Response frequency (Infected birds / Vaccinated birds) Response amplitude (Average oocyst production per bird) E. maxima E. tenella E. acervulina E. maxima E. tenella E. acervulina Oocysts 6 / 15 (40%) 7 / 15 (47%) 13 / 15 (87%) 7.67 x 10⁴ 1.26 x 10⁵ 8.46 x 10⁴ Sporocysts 15 / 15 (100%) 15 / 15 (100%) 15 / 15 (100%) 2.51 x 10⁵ 4.83 x 10⁵ 1.90 x 10⁵ Improvement 60% 53% 13% 3.3 times 3.8 times 2.24 times No oocysts were observed in the intestinal contents of untreated control birds, and the positive controls, inoculated via eye drops, produced higher infectivity frequencies and amplitudes than the experimental spray treatment groups. These results indicate that the gel-formulated sporocyst outperformed the oocyst only in response frequency and amplitude. GENERALIZED STATEMENTS OF THE DESCRIPTION The following numbered statements provide a general description of the description and are not intended to limit the appended claims. Declaration 1: A system for administering a gel to a surface comprising: a first container containing a binding / crosslinking agent in a first solution; a second container containing a gelling component in a second solution; and a delivery device in fluid communication with the first and second containers, the delivery device having an outlet. Statement 2: The system of statement 1, whereby when the first solution is moved from the first container to the outlet of the delivery device to create a first spray at a fixed location, and the second solution is moved from the second container to the outlet of the delivery device to create a second spray at the fixed location, the first and second solutions react to form a gel at the fixed location. Declaration 3: The system of any of the declarations 1-2, wherein the gelling component is sodium alginate and the binding / crosslinking agent is calcium chloride. Statement 4: The system of any of statements 1-3, wherein the first solution or the second solution further comprises a product of interest such as a solution or suspension. Declaration 5: The system of declaration 4, where the product of interest has application in at least one of a group of industries consisting of: food, agricultural, manufacturing, chemical, biochemical, military, aerospace, pharmaceutical, nutraceutical, cosmetic, printing or a combination thereof. Declaration 6: The system of declaration 4, where the product of interest is an edible, herbicide, pesticide, drug, biological product, cosmetic, nutraceutical, pharmaceutical product, coating, ink, paint or a combination thereof. Declaration 7: The system of declaration 4, where the product of interest is a vaccine. zccnnn / ίζηζ / E / γι Declaration 8: The system of declaration 7, wherein the vaccine comprises oocysts. Declaration 9: The system of any of declarations 7-8, wherein the vaccine comprises sporocysts. Declaration 10: The system of declaration 3, wherein calcium chloride is present in a concentration of approximately 1% to approximately 5%. Declaration 11: The system of declaration 3, wherein sodium alginate is present in a concentration of approximately 0.5% to approximately 5%. Declaration 12: The system of any of declarations 1 to 11, wherein the delivery device is a sprayer. Declaration 13: A method for administering a gel to a surface comprising the following steps: providing a first container containing a binding / crosslinking agent in a first solution; providing a second container containing a gelling component in a second solution; providing a delivery device in fluid communication with the first and second containers; moving the first solution from the first container through the outlet of the delivery device and onto a surface at a fixed location; and moving the second solution from the second container through the outlet of the delivery device and onto the surface at the fixed location to form a gel. Statement 14: The method of statement 13, wherein the first solution or the second solution further comprises a product of interest such as a solution or suspension. Declaration 15: The method of declaration 14, wherein the product of interest has application in at least one of a group of industries consisting of: food, agricultural, manufacturing, chemical, biochemical, military, aerospace, pharmaceutical, cosmetic, nutraceutical, printing or a combination thereof. Declaration 16: The method of declaration 14, wherein the product of interest is an edible, herbicide, pesticide, drug, biological product, cosmetic, nutraceutical, pharmaceutical product, coating, ink, paint, dye, or a combination thereof. Statement 17: The method of statement 14, where the product of interest is a vaccine. Declaration 18: The method of declaration 17, wherein the vaccine comprises oocysts. Declaration 19: The method of any of declarations 17-18, wherein the vaccine comprises sporocysts. Declaration 20: An in situ formed gel solution wherein the gel is formed by a first solution containing a binding / crosslinking agent applied to a surface in a fixed location and a second solution containing a gelling component applied to the surface in a fixed location. zccnnn / Lznz / Em It should be understood that the preceding description is only representative of modalities and illustrative examples. For the reader's convenience, the above description has focused on a limited number of representative examples of all possible modalities, examples that teach the principles of the description. The description has not attempted to exhaustively enumerate all possible variations or even combinations of the variations described. The fact that alternative modalities have not been presented for a specific part of the description, or that other undescribed alternative modalities may be available for a part, should not be considered a foregone conclusion regarding those alternative modalities. A person skilled in the art will understand that many of these undescribed modalities involve differences in technology and materials rather than differences in the application of the principles of the description.Therefore, the description is not intended to be limited to less than the scope set forth in the following claims and equivalents. INCORPORATION FOR REFERENCE PURPOSES All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, the mention of any reference, article, publication, patent, patent publication, or patent application cited herein is not, and should not be taken as, an acknowledgment or any form of suggestion that they constitute a valid prior art or form part of the common knowledge in any country of the world. It should be understood that, although the descriptive specification has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate, and not limit, its scope. Other aspects, advantages, and modifications are within the scope of the claims set forth below.All publications, patents, and patent applications cited in this descriptive memorandum are incorporated herein by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. zccnnn / ίζηζ / Β / γι NOVELTY OF THE INVENTION
Claims
Having described the present invention as above, the following claims are considered novel and therefore claimed as property: CLAIMS 1. A system for administering a gel to a surface, characterized in that it comprises: a first container containing a binding / crosslinking agent in a first solution; a second container containing a gelling component in a second solution; and an administration device in fluid communication with the first and second containers, the administration device having an outlet.
2. The system according to claim 1, characterized in that when the first solution is moved from the first container to the outlet of the delivery device to create a first spray at a fixed location, and the second solution is moved from the second container to the outlet of the delivery device to create a second spray at the fixed location, the first and second solutions react to form a gel at the fixed location.
3. The system according to claim 1, characterized in that the gelling component is sodium alginate, and the binding / crosslinking agent is calcium chloride.
4. The system according to claim 1, characterized in that the first solution or the second solution further comprises a product of interest such as a solution or suspension.
5. The system according to claim 4, characterized in that the product of interest has application in at least one of a group of industries consisting of: food, agricultural, manufacturing, chemical, biochemical, military, aerospace, pharmaceutical, nutraceutical, cosmetic, printing or a combination thereof.
6. The system according to claim 4, characterized in that the product of interest is an edible, a herbicide, a pesticide, a drug, a biological product, a cosmetic, a nutraceutical, a pharmaceutical product, a coating, an ink, a paint, or a combination thereof.
7. The system according to claim 4, characterized in that the product of interest is a vaccine.
8. The system according to claim 7, characterized in that the vaccine comprises oocysts. zccnnn / Lznz / B / Yi 9. The system according to claim 7, characterized in that the vaccine comprises sporocysts.
10. The system according to claim 3, characterized in that calcium chloride is present in a concentration of approximately 1% to approximately 5%.
11. The system according to claim 3, characterized in that the sodium alginate is present in a concentration of approximately 0.5% to approximately 5%.
12. The system according to claim 1, characterized in that the administration device is a sprayer.
13. A method for administering a gel to a surface, characterized in that it comprises the following steps: providing a first container containing a binding / crosslinking agent in a first solution; providing a second container containing a gelling component in a second solution; providing a delivery device in fluid communication with the first and second containers; moving the first solution from the first container through the outlet of the delivery device and onto a surface at a fixed location; and moving the second solution from the second container through the outlet of the delivery device and onto the surface at the fixed location to form a gel.
14. The method according to claim 13, characterized in that the first solution or the second solution further comprises a product of interest such as a solution or suspension.
15. The method according to claim 14, characterized in that the product of interest has application in at least one of a group of industries consisting of: food, agricultural, manufacturing, chemical, biochemical, military, aerospace, pharmaceutical, cosmetic, nutraceutical, printing or a combination thereof.
16. The method according to claim 14, characterized in that the product of interest is an edible, a herbicide, a pesticide, a drug, a biological product, a cosmetic, a nutraceutical, a pharmaceutical product, a coating, an ink, a paint, a dye, or a combination thereof.
17. The method according to claim 14, characterized in that the product of interest is a vaccine.
18. The method according to claim 17, characterized in that the vaccine comprises oocysts. zccnnn / ίζηζ / Β / γι 19. The method according to claim 17, characterized in that the vaccine comprises sporocysts.
20. An in situ formed gel solution characterized in that the gel is formed by a first solution containing a binding / crosslinking agent applied to a surface at a fixed location and a second solution containing a gelling component applied to the surface at a fixed location.