WO2013113086A1

WO2013113086A1 - Water-soluble agar polymer film and method for the production thereof

Info

Publication number: WO2013113086A1
Application number: PCT/BR2013/000043
Authority: WO
Inventors: Ricardo YARA.; Cláudia SAMPAIO DE ANDRADE LIMA; Beate SAEGESSER SOS SANTOS; Júlio César BEZERRA PEREIRA
Original assignee: Universidade Federal De Pernambuco
Priority date: 2012-02-02
Filing date: 2013-02-08
Publication date: 2013-08-08

Abstract

The present invention describes a polymer film that is totally water-soluble, hot or cold, which is produced from agar, a natural hydrocolloid polysaccharide widely used in the food industry. The agar has been modified by a hot reaction in acid medium. The change increased the dissolution capacity of the agar in aqueous medium without affecting the property thereof to form films in the presence of a plasticizing agent, since, in the original form thereof, the agar exhibits low solubility in water at ambient temperature and no other film exhibits rapid dissolution for use as a food-product vehicle system. The film produced will serve as support for the incorporation of natural, artificial and/or functional foodstuffs. It may be used, furthermore, in the pharmaceutical industry as a vehicle for active principles. The advantages of using the present film include, notably, the atoxicity and rapid elimination thereof, without metabolization by the organism, in addition to the simple production technology.

Description

Polymeric film of water soluble agar and its obtaining process.

Field of the Invention

The present invention is applicable to the food industry and may also be applied to the pharmaceutical industry for the delivery of products for human or veterinary use.

summary

The present invention relates to a fully water-soluble hot or cold polymeric film produced from Agar, a natural hydrocolloid polysaccharide widely used in the food industry. The film produced will serve as support for the incorporation of natural, artificial and / or functional foods. Can be used in the pharmaceutical industry for the delivery of active ingredients.

Background: State of the Art

The composition and technology of obtaining polymeric films for food applications is already widespread in the scientific literature. Specifically, such films are produced with a view to forming coating films to prevent the rapid deterioration of some perishable foods such as fruits, vegetables, meats and dairy products. These films are packaging that maintains mechanical integrity, improves appearance and promotes food maturation. Moreover, these biofilms are edible as they do not offer any harm to consumer health. Natural polymers, such as proteins and polysaccharides, form the basis of these films. All have the important feature of being completely biodegradable within a considerably short period of time.

An example of an edible packaging film is U.S. Patent Glucomannan / polyhydric Alcohol. Composition and Film Prepared Therefrom "(US Pat. No. 4,851,394, July 25, 1989), by Masao Kubodera, which describes glucomannan-based water resistant films, whether or not added to other polysaccharides, including agar.

Brazilian Patent "Starch and / or Starch Biodegradable Film Containing Natural Antimicrobial Ingredients and Their Uses" (Patent No. PI0704589-1, 13 Apr. 2007), by Carmen Tadini et al., Describes films made with the addition of antimicrobial natural extracts, intended for use as active and / or intelligent packaging for perishable products and / or in the preparation of products for decorative purposes.

The Brazilian patent entitled "Flexible, edible and biodegradable starch and gelatin based bioplastic obtained by thermoplastic extrusion followed by blowing" (Patent No.: PI0901408-0A2, Dec. 14, 2010), by Fakhouri et al., Describes the industrial scale production of flexible films by conventional extrusion without the use of any solvent from natural polymers (starch and gelatin), whether or not containing fatty acids.

Biofilm formation involves the addition of a plasticizer to the polymer. The most commonly used substances in this function are polyalcohols, such as glycerol, triacetin, sorbitol, xylitol, maltitol and mannitol. Plasticizers reduce intermolecular forces and increase the mobility of polymer chains, reducing possible discontinuities and brittle zones. They favor the transition of the material from a vitreous state to a rubbery or gummy state, with greater molecular mobility and, consequently, greater flexibility. In addition to plasticizers, other technological aids may be incorporated into the biofilm composition, such as antimicrobials, antioxidants, emulsifiers, anti-humectants, flavors and dyes. These adjuvants allow the films to be adapted to the demand and industrial interests by maintaining and improving the physicochemical and microbiological qualities of foods.

To biofilms, it is also possible to add, depending on the proposed objective, some nutrients and chemicals pharmacologically active. As has been reported in several scientific articles and international patents, the use of polymeric films already has several applications for the pharmaceutical sciences. Some products consisting of rapidly disintegrating oral or sublingual drug delivery films are sold commercially in many developed countries, such as the United States, Japan, and Italy. Such films have the shape, size and thickness of postage stamps and contain unit doses of mainly OTC-type commercially available drugs.

Pululan biopolymer is the major filmogenic compound used in the production of commercial pharmaceutical films. The first

15 A product containing pullulan to be successful in the US market was Listerine PocketPacks, registered and marketed by Warner-Lambert Company, a Pfizer Inc. personal care branch. Listerine PocketPaks are thin films, quickly solubilized by salivary secretion, used for 0 Carry active ingredients that eliminate the bacteria that causes bad breath and promote a feeling of freshness in the oral cavity. The patent entitled "Fast dissolving orally consumable film" (US Patent No. 7,025,983, April 11, 2006) to Leung et al. Is the document on which this product is based.

5th

In addition to pullulan as a polymeric base, other substances may be used or added in the production of fast dissolving films, such as polysaccharides, preservatives, salivation stimulants, flavorants, sweeteners and pharmacologically active substances. The following patents are cited as references: "Toshio Miyake" Shaped Matters of Tobaccos and Process for Producing the Same (US Pat. No. 4,018,233, April 19, 1977); "Pullulan Binder and Its Uses" (US Pat No. 5,411,945, May 2, 1995) and "High Pullulan Content Product, and Its Preparation and Uses" (US5 Pat No. 5,518,902, May 21, 1996), by Yoshihide Ozaki et al .;

Tobacco Compositions (WO Pat No. 2005/046363, May 26, 2005), US Smokeless Tobacco Company. "Water Soluble Film for Oral Administration with Instant Wettability" (US Pat. No. 6,709,671, Mar 23, 2004), by Horst Georg Zerbe et al., Discloses the invention of water soluble films for instant oral administration. wettability. These are compositions containing therapeutic agents and breath freshening agents produced by the coating technique. The invention relates to the use of water soluble polymeric agents as film formers, the water soluble cellulose-derived polysaccharides being described as ideal for the composition.

The US patent "Fast dissolving films and coatings for controlled release of flavors, active pharmaceutical ingredients, food substances, and nicotine" (US Pat No. 2009/0253754 Al, Dec 04, 2008), by Francesca Selmin et al., Describes a film fast dissolving material to be used as a support for the release of materials into the oral cavity and the processes for producing it. The film composition comprises a cellulose derivative film forming agent such as hydroxypropyl methyl cellulose (HPMC) preferably. A plasticizer is also added; and a rapidly dissolving water-soluble compound, such as the synthetic polyethylene glycol-polyvinyl alcohol copolymer (Kollicoat IR) or sodium alginate. The components are mixed in an emulsifying process without heating, forming the film by drying at room temperature.

Self-Supporting Films For Pharmaceutical And Food Use (WO Pat No. 2005/039543, Oct. 27, 2004), by Cilurzo et al., Uses maltodextrin as a filmogenic agent. The dextrose content in the maltodextrin used is between 11 and 40 molecular units. Its concentration in the composition varies between 40 and 80% of the total mass of the film. Also used is a plasticizer in a concentration of 15 to 55% and active ingredients for food and pharmaceutical use in amounts of 0.05 to 30% by mass. To improve the preservation of films, the patent describes the need for the use of some technological aids, such as the following anti-wetting agents: microcrystalline cellulose, colloidal silica and talc. The formation of fast dissolving films by the use of modified starches is also described in the European patent "Quick water-dissolving film containing cosmetic, aromatic, pharmaceutical or food substances and process for making the same" (No. EP1417895, 12 May 2004), by Marco Pinna and Fausto Pinna. The invention uses oxidized starch associated with a type of soluble cellulose and various other polymers, such as polyvinyl alcohol (PVA), added plasticizers and some adjuvants. The patent claims films for use as foodstuffs in the delivery of food bacteria and probiotic, prebiotic and symbiotic type products. The production process is simple and fast.

European patent "Quick water-dissolving edible anti-hunger film containing fibers that swell in the presence of water" (EP 1738656 BI, Jan 04, 2007), also by inventors Marco Pinna and Fausto Pinna, describes partially soluble edible films in water or in contact with human saliva. The films described in this patent are similar to the previous patent, but differ in composition with respect to the addition of at least one natural food fiber, such as chitosan, glucomann and inulin, which are water insoluble and have the property of swelling, promoting a feeling of satiety to the consumer. Brazilian Patent "Pharmaceutical Form for Oral Administration of Veterinary Medicinal Products" (Patent No.: PI0802711-0A2, July 22, 2008), by Katia Sardinha Bisnoto, describes an edible cellulose film containing doses of a suitable active ingredient as well as It is a gelling element that acts as an adherent and dissolubilizer by the animal's saliva, as well as components necessary for the structural composition of the pharmaceutical form and attractive elements.

U.S. Patent entitled "Oral pharmaceutical formulations containing non-steroidal anti-inflammatory drugs and acid inhibitors" (No. 2007/0154542 Al, Dec. 15, 2006), by James B. Tananbaum et al., Reports pharmaceutical compositions containing one or more more non-steroidal anti-inflammatory or acid inhibitors in the form of orally dissolvable films. The invention claims within limitations, the use of surfactants and plasticizers, type polyalcohols.

Rapidly disintegrating sheet-like presentations of multiple dosage units (US Pat No. 5,629,003, 13 May 1997), to Michael Horstmann et al., Discloses a rapidly dissolving film in the form of slides in unit presentations. multi-dose. The product is characterized by having a film former, specifically acetylated starch, in the proportion of 20-60% by mass, 2-40% of a gel former, 0.1-35% of active ingredients and above 40%. % inert filler excipients further describes the use of 40% polar solvent and includes processing to form a homogeneous, spreadable extrudable mass.

The present invention utilizes as the base raw material in film production the polysaccharide known as agar, also simply called agar. According to literature data, the agar is a phycocolloid, a seaweed-based gel-forming substance that has the oldest and best-researched industrial application in the world, and was the first product to be used in the field. food as a gelling agent. The agar gel can be obtained in very dilute solutions containing a fraction of 0.5% to 1.0% of the raw material. Agar in industry is a technological aid, with the following main functions: gelling, thickening, texturizing and stabilizing. Another popular application of agar is as the main solid culture medium used in microbiological studies and research.

The medicinal use of agar is also cited because of its classification as a soluble dietary fiber. The definition of dietary fiber, according to the report of the Board of Directors Committee of the American Association of Cereal Chemists (AACC Report. The Definition of Dietary Fiber. Cereal Foods World. Vol. 46, No. 3, Mar. 2001), Freely translated as: "Food fibers are the edible parts of vegetables or similar carbohydrates that are resistant to digestion and absorption in the human small intestine, having full or partial fermentation in the large intestine. Dietary supplements include polysaccharides, oligosaccharides, lignin and associated plant substances. Dietary fibers promote beneficial biological effects, including laxation, and / or attenuation of plasma cholesterol and / or glucose levels. "Agar has the ability to increase volume and promote fecal bolus hydration, aiding in the regulation of intestinal transit, with mechanical and peristaltic reflex reflex excitation of the intestinal contractions When ingested, the agar has a digestibility of only 10% and a calorie content close to zero.These characteristics make it ideal as a raw material of food and drink for diabetics and people on diets. It is known that agar causes delayed gastric emptying, which may prolong the feeling of satiety after a meal. [8] The 2004 study by Maeda et al evaluated the effectiveness of a diet based on agar in combination with a conventional diet (traditional Japanese food) in obese patients with impaired glucose tolerance and c with type 2 diabetes. Agar diet resulted in remarkable weight loss due to the maintenance of reduced calorie intake and promoted a significant improvement in the general conditions of the metabolic syndrome, with reduction in the values of the following physiological parameters: systolic and diastolic blood pressure; hemoglobin-bound glucose and plasma cholesterol.

The general characteristics of the agar are: non-toxic to most microorganisms and humans; melting point between 95 and 100 ° C and gelling at about 45 ° C; remain stable even under sterilization temperatures (120 ° C); It is physiologically inert since a small number of bacteria produce enzymes capable of promoting their hydrolysis.

Agar agar is a hydrocolloid embedded in the crystallized cellulose fibers of the cell walls of red agarophyte seaweed (Rhodophyceae family). Agar basically consists of a heterogeneous mixture of two reserve polysaccharides: agarose and agaropectin. Agarose is the gelling portion of agar and represents on average 70% of total matter. Chemically, agarose is a neutral linear polymer made up of repeated agarobiose units, which in turn consists of a β-D-galactopyranose molecule bound 1 → 4 to an α-agarose molecule. 3,6-anhydro-L-galactose. These repeated units are linked 1 → 3 to form agarose. Agaropectin, a non-gelling fraction, is a sulfated polysaccharide (3% to 10% sulfate) composed of agarose and varying percentages of sulfate ester, D-glucuronic acid and small amounts of pyruvic acid.

The agar is insoluble in cold water, but it expands considerably and absorbs about 20 times its own weight. The average molecular weight of agar varies from 8,000 to over 100,000D. Dissolving in hot water is relatively rapid, promoting firm gel formation even at low concentrations. This gel is thermo-reversible and is formed because agarose molecules have a double helix structure which aggregates to form a three-dimensional structure that holds water molecules in their interstices. The strength of the gel is influenced by the following factors: concentration, time, pH and sugar content. The decrease in pH causes a noticeable reduction in gel strength. Agar solutions exposed to high temperatures for prolonged periods may degrade, resulting in decreased gel strength.

There are some types of modified agar on the market that have the property of dissolving completely in water at a lower temperature and time than conventional. Examples include the following products:

(1) "Grand Agar", by the Spanish company Hispanagar. It has the characteristic of dissolving in water at a concentration of 1% at a temperature of 87.5 ° C;

(2) "Speed Agar-80", by the Japanese company Taito. At a concentration of 1%, it solubilizes completely at 75.6 ° C.

(3) Quick Soluble Agar (QSA), a registered product of Setexam Company of Morocco and patented in March 1996 by the document entitled "Production Process of Quick Soluble" (US Pat No. 5,496,936, Mar. 5, 1996), by Thami. et al. QSA is produced by an extrusion technique that modifies the agar making it able to fully solubilize within 5 minutes by heating to 75 ° C.

(4) "Low gel strength agar" produced by Ina Food Industry Co., Ltd., described in the "Low gel strength agar-agar" patent (US Patent No. 5,502,181, Mar. 26, 1996), Kojima et al. This agar was produced by controlled acid partial hydrolysis modification of the feedstock, followed by neutralization and drying. The purpose of the process is to obtain a product with a gel strength of 10 to 250 g / cm2, at a concentration of 1.5%, to be used as a thickening and soft gel forming agent (without syneresis) in cosmetic and food products.

(5) "Takara Agaoligo" is a powder product, registered by the Japanese company Takara Shuzo Co., Ltd. The creators claim, based on various published scientific studies, that the product has pharmacological properties. Agaoligo is formed from agar as a raw material for obtaining, by controlled partial acid hydrolysis, oligo polysaccharides called "agarooligosaccharides" (AOS). The hydrolysis can be performed using acid ion exchange resins as described in Tatsuji Enoki et al., "Agarobiose-containing composition" patent (US Pat. No. 7217817, 15 May 2007) to obtain a product containing 5 to 10 60% (w / w) agarobiose and 40 to 95% (w / w) of at least one other agaroligosaccharide. Under weak and high temperature acid conditions, the α-1,3 bonds between anhydrogalactose and agarose galactose are hydrolyzed to produce their lower polymerization derivatives. OSA is composed mainly of agarobiose, agarotetraose, agaroexaose and agarooctaose, all containing anhydrogalactose at the reducing terminals. Takara Agaoligo is a mixture of these AOS.

OSA has been shown to halt the production of Prostaglandin E2 and pro-inflammatory cytokines such as Tumor Necrosis Factor α (TNF-α), which is considered the cause of rheumatism. In 2004, the study by WANG et al. found that OSA exhibits antioxidant activity in eliminating hydroxyl free radicals and superoxide anion radicals and inhibiting peroxidation lipid. The same researchers confirmed, in vivo and in vitro, the antitumor, antioxidative and immune enhancement activities of OSA produced by enzymatic hydrolysis. In 2007, CHEN et al. found that OSA has anti-angiogenic effects, which are associated with induction of endothelial cell apoptosis.

According to reports dated 2001 and published by the Food and Drug Administration (FDA), under the heading of "Premarket Notification of New Dietary Ingredients. Agaroligosaccharides", acute oral toxicity studies confirm that OSA has no effect. mutagenic or carcinogenic or any significant adverse effect. The OSA LD50 has been shown to be greater than 2,000mg / kg.

15

Prior Art Problems and Limitations

Among the film-forming biopolymers, starch stands out, which is of low cost and high availability in the market, has widespread application in the food industry.

However, starch-based films and derivatives, as previously described in WO Pat. Nos. 2005039543, EP1417895 and EP 1738656, are quite unstable to changes in humidity and temperature due to the hydrophilic and semicrystalline nature of these biopolymers. Such characteristics make storage, technology for obtaining and short-term commercial application of starch films very difficult. In addition, the use of additional ingredients is necessary to preserve their characteristics under different storage conditions.

0

The pullulan polymer is also of natural origin, but it is a high cost material and difficult to obtain. Cellulose-derived polymers, on the other hand, are of semi-synthetic origin and need, in the vast majority of cases reported in the literature 5 (see US Pat No. 5,948,430 and US Pat No. 2009/0253754 Al), to be associated with other water-soluble materials. to obtain products with adequate characteristics of mechanical resistance and stability to environmental changes. All previously patented works utilize water-soluble polymers in the formation of fast dissolving films. However, none of them describe agar as an alternative raw material because it in its original form has low solubility in water at room temperature.

No previously described patent discloses the application of fast dissolving films for use as a food and beverage delivery system for hot and cold water and beverage preparation for extemporaneous consumption. Films are therefore an alternative to common commercial food powders and granules, conveying fixed quantities of certain products. Objectives of the Invention

The aim of the present invention is to present a new product and manufacturing process for polymeric films using modified agar as the main component, and to solve the following problems presented in the state of the art: difficulty in handling, storage and portability of some food and pharmaceutical products. in the form of powders and granules; low solubility of agar in cold water; difficulty in obtaining some raw materials for the production of commercially available films, such as pullulan; the high energy value of starch based films and derivatives.

Solution

The technique described in the present invention promotes modification of the agar molecule using a low pH acid reaction medium (0 - 3). In this reaction, partial hydrolysis of the agar chains occurs forming derivatives with various chain sizes. The change increased the ability of the agar to dissolve in aqueous medium without affecting its film-forming property in the presence of a plasticizer.

The invention described herein demonstrates by simple technique and using low cost equipment and inputs, the transformation of agar into a highly water soluble compound at any temperature.

The product of this invention, as it has a low metabolism index during digestion, can additionally be used as a vehicle for extemporaneous use in low calorie diets and as a vehicle for medicinal products for human or veterinary use, including diabetes patients.

Benefits

The use of fast dissolving agar films makes the preparation of food drinks much more practical, especially for children, the elderly, people with neurodegenerative diseases and people with physical and cognitive disabilities, as it facilitates their handling without causing waste for losses. Each agar film will be presented as an individual slide containing a standardized amount of product, which will be packaged per unit or in multi-dose. The preservation of the films, when kept in proper packaging, is superior to conventional commercial powders and granules. The intrinsic characteristics of the agar predict that the films based on this material are less susceptible to microbiological and morphological changes due to ambient humidity and temperature elevation than powders and granules in general, making the product of this invention even safer in terms. preservation of the products conveyed by this film. The invention relates to the production of agar-based polymeric films having the following characteristics: short-term dissolution (up to 3 minutes) in water at any temperature; good mechanical properties of strength and flexibility; pleasant organoleptic aspects after dissolution in water, with adequate palatability and which do not add to the possible products conveyed no significant change in appearance; wide stability to the ambient variations of temperature and humidity, conserving in the long term its intrinsic characteristics; economically viable production chain with low environmental impact.

The simplest biofilm production technique, applied on a laboratory scale, is called "casting". This is the technique used in forming the agar biofilms described herein, in which a filmogenic solution with water is prepared and then applied to an inert support and dried for solvent evaporation. It is an inexpensive technique because it demands less equipment and resources compared to other production techniques. The film may be made or cut to the size, shape or thickness desired for its intended purpose. Agar also has the advantages of being a 100% natural product, free of toxicity and practically unabsorbed by the gastrointestinal system. Both agar and other components of this formulation are readily available from the market without the risk of supply problems.

The agar-based film is a great business opportunity in view of its technological and commercial appeal, as it is a differentiated product. Rapidly dissolving films are part of a still growing market worldwide and are little explored in Brazil. Research by Technology Catalysts predicts that the estimated $ 500 million soluble film pharmaceutical market in 2007 could reach $ 2 billion in 2012. [9] Based on the growth trend of the last decade, this market can reach revenues of up to $ 13 billion by 2015.

Agar film may also serve as a support for the delivery of pharmacological active ingredients. The thin films of Rapid dissolution is therefore a modern and innovative pharmaceutical form for drug delivery. Pharmaceutical use of agar films may be direct or indirect. Direct use refers to the administration of medicines through mucous tissues of the human body, such as buccal, ocular, vaginal, urethral and rectal mucosa. With the advantage over traditional forms (tablets, capsules, gels, eye drops, suppositories and eggs) of more practical and intuitive administration, they can be used more easily in pediatric, geriatric, physically and / or cognitively disabled patients and patients. with neurodegenerative disorders (parkinsonism, Alzheimer's syndrome and schizophrenia, for example). The biofilms can be placed directly in the buccal region, over or below the tongue, so that salivary secretion can promptly promote its dissolution, without requiring the obligatory consumption of water. This form of administration facilitates use by people with impaired swallowing (dysphagia). Administration of the films through these routes allows the absorption of the drug directly into the bloodstream, without affecting the digestive enzymes or first pass effect on the liver. Thus, films are faster, safer, and more effective forms than traditional pharmaceutical forms because, in comparison, they reduce the dose required for the effect of the drug. Another advantage of oral application of agar films is that, due to its virtually absent enzymatic digestion by bacteria, it can be considered a non-cariogenic product, reinforcing its applicability as a pediatric product. Thus, fast dissolving films represent an association of the efficiency of a liquid pharmaceutical form with the practicality of a solid form.

The patent also claims the use of agar films as a pharmaceutical form for indirect use. Biofilms can serve as a support for principle active delivery, which would require prior dissolution in hot or cold water, in order to promote the reconstitution of the oral drug in solution or suspension forms for extemporaneous use. Agar films are more stable, better conservable and faster dissolving than reconstituting powders and granules conventional. They are also products capable of delivering precise doses of one drug per slide unit, when production uniformity is guaranteed. Agar films would allow information and images to be printed on their surface using edible inks. Such information may be, for example: company logo, quantity or dose per unit, net weight, composition, warnings and warnings, various symbols and drawings.

The application of films for food products, as described for pharmacists, can be for direct, oral or indirect consumption, being pre-solubilized in cold or hot water or placed on food, and may even go through any process. cooking. In addition to serving as food support, the films can be applied and used for decorative purposes, according to the creative process of the user.

The novelty and the technical effect achieved

In summary, the novelty of the present invention is the use of the modified agar as a fast dissolving polymeric film based raw material and the process for its production. Agar modification by acid ensures the production of flexible and resistant films that are easily soluble in water at any temperature.

Detailed Description Like any polysaccharide, agar is described by the scientific community as a product that can undergo a hydrolysis reaction resulting in a decrease in its molecular weight and hence its gelatinizing power. Partial and controlled agar hydrolysis may be performed by the following methodologies or combinations thereof: (1) acid hydrolysis, (2) alkaline hydrolysis and (3) enzymatic hydrolysis. The acid hydrolysis production process uses steps already established in the literature [1, 2, 3]. In this patent, we apply some methodological variations that give the final product the following presentation: films (films, strips) with good strength and flexibility mechanical properties, based on agar, having a short time dissolving capacity in water at any temperature. For the production of modified acid partial hydrolysis agar films, the inventors generally proceeded as follows:

1) In an inert, high temperature resistant container, the agar was dispersed in a ratio of 0.5 to 2g per 100 ml of water under constant agitation. It was then heated to boiling for total solubilization of the material, with a reduction of 50 to 70% of the initial volume. The gel formed was named phase A. 2) In another inert, high-temperature-resistant container, the acid was stirred and heated in the same proportion as phase A. Hot acid can be named phase B. The technique allows variation of the amount of the amount of phase A in the ratio of 3 parts to each part of acid (phase B).

3) The hot (phase A) gel was slowly dripped into the acid (phase B). The obtained mixture was continuously stirred and evaporated to 50 to 90% reduction of the total volume. Throughout the hydrolysis process, the reaction medium was kept in a pH range between 0 and 3.

4) The same volume of water was added to the solution resulting from step 3, followed by evaporation to 40 to 60% by volume. This process was repeated 3 to 5 times or until the soluble polymer chain was obtained. The end point of the reaction can be determined by sampling to verify the solubility of the agar in cold water.

5) Then, to promote precipitation of the compounds, isopropyl alcohol was added in a ratio of 0.7 to 0.9 volumes for each volume of the solution described in item 4, or alternatively, ethyl alcohol in the ratio of two to four volumes for each volume of the solution described in item 4. The mixture was cooled to a temperature between -30 ° C and + 8 ° C until total precipitation of the material.

6) The precipitated material is a dense, slightly yellowish white solid, which was isolated by centrifugation between 380 and 10,000 g (Rcf) for a period of 5 to 30 minutes, depending on the amount. The supernatant was gently discarded to avoid product loss. Alcohol was added for resuspension of the material which was centrifuged again as often as necessary until elimination of residual acid.

7) The acid-free product, called modified agar, may be dried to reserve for later use or a glycerol solution may be added thereto, in the ratio of 0.05g to 0.20g for each gram ( g) modified agar or even another plasticizing agent for obtaining the film. The mixture was brought to the circulating and renewed oven at a constant temperature of 38 to 45 ° C for a period of 16 to 24 hours.

As a particular form of the modified agar film formation process: 1) In a 250.0 ml beaker, 1.0 g of agar (Bacteriological Agar) was dispersed in 100.0 ml of distilled water. A magnetic bar was placed inside the container. Then, with the aid of a heated stirrer plate (18cm xllcm), heating was performed at a temperature around 100 ° C, and vigorous stirring until the material was completely solubilized (approximately 30 minutes). The gel formed was named with the letter A.

2) Thus, in another 250.0 ml beaker, named with the letter B, 30.0 ml glacial acetic acid PA was placed under stirring and heating inside a chemical fume hood. The still-hot agar gel (A) was slowly dripped into the acid (B). The mixture was evaporated until the volume reached a value of approximately 25.0 mL, which yielded a warm-up time of about 20 minutes.

3) To the resulting solution from the previous step, 40.0 ml of distilled water was added and evaporation was awaited to about

25.0 mL (approximately 20 minutes of heating). This step (addition of water and evaporation) was repeated two more times, resulting in a total heating time of the mixture of approximately 80 minutes. Heating the agar solution to very low pH (approximately 1) at a temperature around 100 ° C led to the generation of compounds with different chain sizes.

4) The solution containing a volume of about 25.0 mL was removed from the hot plate and allowed to fully return to room temperature. Then, P.A. isopropyl alcohol was added in the ratio 0.9: 1, ie the amount of approximately 22.0 mL. The mixture was placed in the freezer and the material produced was expected to precipitate for at least 24 hours.

5) The freezer container was removed and found to have formed a slightly dense, slightly yellowish white bottom body. Light agitation was performed with the aid of a glass rod and the entire product was transferred to a 50.0 ml Falcon centrifuge tube. The material was centrifuged at 1920 g for 20 minutes at 8 ° C in a centrifuge (Universal 320R, Heltich Zentrifugen). At the end of the process, the supernatant was gently discarded to avoid product loss. About 10.0 mL of P.A isopropyl alcohol was added to the centrifuged material. The material was agitated on an HP56 tube shaker (Phoenix), promoting full dispersion and centrifugation again. Washing of the product with isopropyl alcohol was repeated at least once more to ensure elimination of all acetic acid residue in the sample.

6) In the Falcon tube itself, 20.0 mL of distilled water was added to the product. With the aid of the tube shaker, the sample was stirred until the material was completely solubilized. The formed solution was taken to a 100.0mL beaker, a magnetic bar was added and Stirring was performed using a plate. Then 0.75mL of glycerol solution (Bidistilled glycerin) was dripped at a concentration of 20% (w / v). The mixture was poured into a 6.0 cm diameter x 1.0 cm high mold and brought to the circulating and renewing oven (TE-394/3, Tecnal) at a constant temperature of 45 ° C. ° C for a maximum of 20 hours. Drying time may vary from 1 hour upwards or downwards. Some polymer hydrolysis processes and film formation processes are cited and recognized in the literature, such as: use of wet heat from pressurized water vapor (autoclaving); microwave heating; condensation reflux system; heating by immersion technique (water bath); acid catalysis by cationic ion exchange resins, fibers or membranes; application or association of hydrolysis in alkaline medium; application or association of hydrolysis by enzymatic action; application of ultrasonic vibration (ultrasound); application of electromagnetic waves; application of unbalanced plasma; electrochemical processes; simple or complex coacervation; roller, drum or spray-dryer extrusion and processing system.

The present invention applies the direct heating process in acid reaction medium to promote partial agar hydrolysis and the casting technique to induce film formation. These are the most economical processes and technologies that are most easily adaptable to industry.

The state of the art of this invention dictates that the agar, to be subjected to the partial acid hydrolysis process, must be fully solubilized in the aqueous medium and without any color change upon heating. These factors are preponderant to the proper progress of the process. It was decided that the acid required for the hydrolysis reaction should be selected from those that have application in the food or medicine industry, for example: hydrochloric acid; sulfuric acid; nitric acid; phosphoric acid; Acetic Acid; trifluoroacetic acid; Citric acid; fumaric acid; malic acid; acid formic; Tartaric acid; lactic acid; Ascorbic acid. The acids may be used at any concentration to obtain an initial reactive solution with a pH between 0 and 3, preferably less than 1. To obtain the product developed in this invention, the best result was obtained when using glacial acetic acid PA

After the desired hydrolysis period, residual acidity should be eliminated using a volatile solvent. The following solvents may be used but the technique is not limited to them: ethyl alcohol, acetone and isopropyl alcohol. The latter being the most suitable for the process. The solvent precipitates the modified agar and extracts the acid from the reaction medium after its application in successive washes of the material. The solvent used may be recovered and reused for the same purpose.

To facilitate and expedite the filmmaking process described in this invention, the modified and purified agar can be oven temperature controlled drying with air circulation and renewal of 38 ° C to 45 ° C for 8 to 12 hours as a step optional process. It can then be crushed (pulverized) using appropriate instruments and stored in a moisture free environment protected from light and high temperatures. The stored powder will serve as raw material for subsequent resolubilization in water and addition of the plasticizing agent.

The agar used as the base raw material for film production can be obtained from species recognized as biopolymer producers, mainly from the botanical genera Gelidium and Gracilaria, according to the traditional techniques of industrial or master production, observed in the literature [4 ].

In addition, one or more water-soluble or water-dispersible polymers in any proportion may be included in the modified agar film composition in order to promote adjustments in their physicochemical characteristics. Examples of polymers suitable for this purpose but not limited to: starches and derivatives (modified and pregelatinized; dextrins; celluloses and derivatives (e.g. hydroxypropyl methyl cellulose, hydropropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose); pectin; proteins and derivatives (eg gelatin, casein, collagen, zein); polyvinyl pyrrolidone; polyvinyl alcohol; alginic acid and derivatives; natural gums (e.g., guar gum, xanthan gum); polyethylene glycol; polyethylene oxide; carrageenan; glucomannan; chitosan; pullulan; fucoidan.

One or more agar film forming agents may optionally be added, preferably from those in the class of polyhydric alcohols and derivatives, which include: glycerol; sorbitol; mannitol; propylene glycol; xylitol, maltitol; galactitol; isomaltate; glycerol triacetate; glycerol tricaprylate; monoacetin; diacetin; triacetin.

In accordance with the intended applications of the film described in this invention, other non-toxic, chemically and physically compatible technological aids may be added to the composition, with no limitation as to the materials employed, their concentrations and associations. For this purpose, emulsifying agents (surfactants, surfactants, disintegrants) are mentioned; flavoring agents; coloring agents (dyes); sweeteners; anti bacteria nos; antifungal agents; antioxidants; fillers; antiumectants; sensory stimulating agent. 5 Several formulations containing agar as a filmogenic agent were produced in triplicate (ANNEX 1, 2 and 3), varying glycerol concentrations and reaction time. The physical and sensory aspects of the films produced were visually evaluated. The following water dissolution test was also performed on the agar films: In a glass beaker containing 50.0mL of cold water (2 to 8 ° C), it was individually stirred with the aid of a magnetic bar and agitator plate means a piece of film obtained approximately 2 cm2 in area. The time required for its total dissolution was timed. In other individual containers containing 50.0mL of hot water (80 to 100 ° C), another same piece of film was placed. Agitation was performed until complete dissolution of the material, whose time was timed and recorded. ANNEX 1

WITH PO NE FORMULA FORMULA IA FORMULA 1B FORMULA 1C FORMULA 1D NTE Standard

Negative

AGAR 1.0g 1.0g 1.0g 1.0g 1.0g

GLYCEROL 0 lOOpL 200 pL 400 pL 800 pL

ACID 30.0mL 30.0mL 30.0mL 30.0mL 30.0mL ACETIC

TIME 20 20 minutes 20 minutes 20 minutes 20 minutes REACTION of minutes

HYDROLYSIS

ANNEX 2

COMPONE FORMULA FORMULA 2A FORMULA 2B FORMULA 2C 2D FORMULA NTE Standard

Negative

AGAR 1.0g 1.0g 1.0g 1.0g - 1.0g

GLYCEROL 0 50pL 100 pL 150 pL 200 pL

ACID 30.0mL 30.0ml_ 30.0mL 30.0mL 30.0mL ACETIC

TIME 20 20 minutes 20 minutes 20 minutes 20 minutes REACTION of minutes

HYDROLYSIS

ANNEX 3

COMPONE FORMULA FORMULA FORMULA 3A FORMULA 3B FORMULA 3C NTE Standard Standard

Negative positive

AGAR 1.0g 1.0g 1.0g 1.0g 1.0g

GLYCEROL 0 150pL 150pL 150 pL 150 pL

ACID 30.0mL 30.0mL 30.0ml_ 30.0mL 30.0mL ACETIC

TIME 20 20 minutes 40 minutes 60 minutes 80 minutes REACTION minutes

HYDROLIE ANNEX 1: The Negative Pattern (no glycerol added) has formed translucent and brittle films that are difficult to remove from the plastic container. Formula IA was the only one that made films, but they were also brittle. The other films (1B, 1C and 1D) formed a viscous gel difficult to extract from the container. Standard and Al films were fully solubilized in hot water in less than 1 minute, but were not fully solubilized in ice water. The film completely disintegrated within 4 minutes on average, but there was still residual, fibrous, unsubstituted appearance. ANNEX 2: The films of the Negative Standard formulas 2A and 2B were translucent and brittle. 2C films showed good flexibility and good sensory appearance, exhibiting low touch viscosity. Dissolution in hot water was rapid in less than 1:00 minute, but dissolution in ice water resulted in the formation of small fibrous-looking residues. The 4D formula did not form film. ANNEX 3: Dissolution in ice water of Positive Standard, 3A and 3B films continued without complete occurrence, although all had good macroscopic appearance, with adequate conditions of flexibility and strength. There was total disintegration of the films in the average times, respectively, 4:00; 3:30 and 2:40 minutes of agitation, but there is still fibrous residue formation in all these samples. It was noted that the amount of insoluble residue was smaller, in a relationship inversely proportional to the reaction time. The 3C films looked great, were translucent and flexible, and had good manual tensile strength. Dissolution in hot water occurred in less than 30 seconds, while dissolution in ice water occurred in less than 2:00 minutes.

Claims

Water soluble agar polymeric film, characterized in that it is obtained by the modification of the agar molecule by hydrolysis in an acidic reaction medium.

Water soluble agar polymeric film according to Claim 1, characterized in that the acidic reaction medium has a pH between 0 and 3.

Water soluble agar polymeric film according to Claim 1 or 2, characterized in that the acid reaction medium is obtained with hydrochloric acid or sulfuric acid or nitric acid or phosphoric acid or acetic acid or trifluoroacetic acid or citric acid or fumaric acid or acid. malic acid or formic acid or tartaric acid or lactic acid or ascorbic acid.

Water soluble agar polymeric film according to Claim 1 or 2, characterized in that the acid used is glacial acetic acid P.A.

Water soluble agar polymeric film according to Claim 1, characterized in that other water soluble or dispersible polymers are added to its composition.

Water soluble agar polymeric film according to Claim 5, characterized in that the additional polymers are modified or pregelatinized starches or derivatives; dextrins, celluloses or derivatives; pectin, proteins or derivatives; polyvinyl pyrrolindone, polyvinyl alcohol, alginic acid or derivatives; natural gums, polyethylene glycol, polyethylene oxide, carrageenan, glucomannan, chitosan, pululan or fucoidan.

Water-soluble polymeric agar film according to Claim 1, characterized in that one or more plasticizing agents for agar film formation are added.

Water-soluble agar polymeric film according to claim 7, characterized in that the plasticizing agents are of the class of polyhydric alcohols or derivatives, including or alone: glycerol, sorbitol, mannitol, propylene glycol, xylitol, maltitol, galactitol, isomaltate, glycerol triacetate glycerol tricaprylate, monoacetin, diacetin or triacetin.

Water-soluble agar polymeric film according to Claim 1, characterized in that the product is compatible with non-toxic technological adjuvants.

Water-soluble agar polymeric film according to Claim 9, characterized in that the adjuvants are emulsifying, flavoring, coloring agents, sweeteners, antibacterials, antifungals, antioxidants, fillers, antiumectants or sensory stimulants.

Process for obtaining the water-soluble agar polymeric film according to Claim 1, characterized in that the agar is placed in a high temperature-resistant inert container in a ratio of 0.5 to 2 g per 100 ml of water under constant agitation. , and then be heated to boiling and complete solubilization of the material, forming a gel.

Process for obtaining the water soluble agar polymeric film according to claim 11, characterized in that the gel formed and acetic acid are placed in another container, varying the amount of gel between 1 and 3 parts, including their limits, for each part of under stirring and heating, slowly dripping the still-warm gel into the acid followed by reduction by evaporation of the total volume of the mixture from 50% to 90%.

Process for obtaining the water-soluble agar polymeric film according to claim 12, characterized in that water in the same volume of solution is added to the solution, followed by evaporation to 40% to 60% by volume and this process is repeated 3 to 5 times. or until the soluble polymer chain is obtained.

Process for obtaining the water-soluble agar polymeric film according to claim 13, characterized in that 0.7 to 0.9 volumes of isopropyl alcohol per solution volume are added or, alternatively, 2 to 2 ethyl alcohol. 4 volumes for each volume of the solution, followed by cooling of the mixture to -30 ° C to + 8 ° C.

Process for obtaining the water-soluble agar polymeric film according to claim 14, characterized in that the material is isolated by centrifugation of between 380 and 10000 g (Rcf) for a period of 5 to 30 minutes and the supernatant is discarded, followed by the addition of alcohol and centrifuged again until residual acid is removed.

Process for obtaining the water-soluble agar polymeric film according to claim 15, characterized in that, to the acid-free product (modified agar), a glycerol solution is added in the ratio 0.05g to 0.20g for each gram ( (g) modified agar or other plasticizing agent, the mixture being oven-circulated and circulating at a constant temperature of 38 to 45 ° C for a period of 16 to 24 hours.

Process for obtaining the water soluble agar polymeric film according to claim 1, characterized in that the film is produced in a 250.0 ml beaker in which 1.0 g of agar (Bacteriological Agar) is dispersed in 100.0 ml of distilled water. Place a magnetic bar inside the container and then, using a heated stirrer plate (18cm x liem), heat at 90 to 110 degrees Celsius and stir the compound until complete solubilization of the material (25 to 35 minutes) forming an agar gel.

Process for obtaining the water-soluble agar polymeric film according to claim 17, characterized in that the film is produced in another 250.0 mL beaker by placing 30.0 mL of PA glacial acetic acid under stirring and heating on the inside a chemical fume hood and slowly dripping the agar gel obtained in claim 17, still warm, into the acid and evaporating the mixture to a volume of 25.0 mL with a heating time of 20 ° C. minutes

Process for obtaining the water-soluble agar polymeric film according to claim 18, characterized in that 40.0 ml of distilled water is added to the solution and evaporation to 25.0 ml (20 minutes of heating) and addition of water and evaporation is repeated twice more, resulting in a total heating time of the mixture of 80 minutes and heating of the agar solution to pH 1 under temperature around 100 ° C.

Process for obtaining the water-soluble agar polymeric film according to claim 19, characterized in that the final solution of acid-hydrolysis-modified agar is removed from the heating plate and expected to fully return to room temperature, followed by the addition of PA isopropyl alcohol in proportion. 0.9: 1, ie the amount of 22.0 ml, and placing the mixture in the freezer, allowing the material to precipitate completely for 24 hours.

Method for obtaining the water-soluble agar polymeric film according to claim 20, characterized in that it is removed from the freezer container, followed by gentle stirring with the aid of a glass rod and transferred to a Falcon-type centrifuge tube. 50.0 mL.

Process for obtaining the water-soluble agar polymeric film according to claim 21, characterized in that the material is centrifuged at 1920 g (Rcf) for 20 minutes at 8 ° C in a centrifuge (Universal 320R, Heltich Zentrifugen) and at the end of process, the supernatant is discarded.

Process for obtaining the water-soluble agar polymeric film according to claim 22, characterized in that about 10.0 ml of isopropyl alcohol PA is added to the centrifuged material, followed by stirring in a fully dispersed HP56 (Phoenix) tube shaker; and further centrifugation, repeating the washing step of the product with isopropyl alcohol once more.

Process for obtaining the water-soluble agar polymeric film according to claim 23, characterized by the addition of 20.0 mL of distilled water to the centrifuged product present in the Falcon tube and stirring of the sample until complete solubilization of the material, leading to the solution formed. to a 100.0mL beaker by adding a magnetic bar and stirring using a plate and then dropping 0.75mL of glycerol solution (Bidistilled Glycerin) at a concentration of 20% (m / v) and pouring the mixture into a mold with dimensions of 6.0 cm diameter x 1.0 cm high, brought to the circulating and renewing oven (TE-394/3, Tecnal) at a constant temperature of 45 ° C for a period of 20 hours, the drying time being 40 minutes to 1 hour and 30 minutes.