|Title of Invention||
BIOACTIVE COMPOSITIONS OF OIL CONTAINING PARTICLES SMALLER THAN ONE MICRON AND PROCESS OF PREPARATION THEREOF
|Abstract||Bioactive composition of oil containing particles smaller than 1 micron and their process of preparation from a variety solid raw materials are described.|
|Full Text||FORM - 2
THE PATENTS ACT, 1970 (39 OF 1970)
" BIOACTIVE OIL COMPOSITIONS FROM SOLIDS AND METHODS OF PREPARATION THEREOF "
DR. SHANTARAM GOVIND KANE, INDIAN NATIONAL, RESIDING
1, INDRADHANUSHYA APARTMENT , AGARKAR ROAD ,
827 / A, SHIVAJI NAGAR, PUNE 411 004 , MAHARASHTRA , INDIA .
The following specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performed:—
This invention relates to novel oil compositions and a method of preparation for the same. The oil compositions are prepared from solids and their suspensions along with or without the simultaneous presence of biomass in various forms. The final oil compositions are substantially free of large particles but retain particles less than I micron in size including nanoparticles in sub-micron range and are useful as medicinal and bio-regulator substance for use by human beings, animals, birds, plants, and all other living forms.The said oil compositions are extracts in oil phase prepared by combining solids and their suspensions with or without additional biomass with oil and water along with other low boiling medium, if any, and heating or boiling below the smoke point of oil to substantially remove all water and then separating the oil composition as an oil phase by filtration from the residue of solids and biomass. .
BACKGROUND OF THE INVENTION
Methods, Compositions, Uses, Potency, Shelf life, Toxicity
Use of solids of different types for effectively treating a variety of conditions and ailments dates back to ancient times.
In Ayurveda, solids have been used in a variety of ways. As an example, metals and minerals are used as raw materials in the preparation of Bhasma , an important class of therapeutic products for the treatment of human ailments. The methods of preparation of Bhasma are very elaborate and lengthy. General information about a variety of such products and there methods of preparation is given in the Encyclopaedia of Indian Medicine [ Sudarshan, 2005]. The final product is obtained as a powder. A variety of metals and minerals , including heavy metals are used in these Bhasma preparations and even in other Ayurvedic products. Based on the recommended daily oral dose of the medicine, the intake of various toxic elements such as Mercury, Arsenic and Lead can be quite high. As a result, there is a serious concern about the potential toxicity of these preparations
( Saper et al., 2004).
Usefulness of a variety of metals, minerals and other solid products in various forms as important providers of a variety of elements as essential nutrients
and micronutirents for the healthy growth and maintainance of health of all living beings including humans , animals and plants is well known in modern science.
The therapeutic dosage of various elements is quite high. For elements such as Gold, Silver, Copper, Zinc, Iron, the typical dose is in mgs /Day. As an illustration, Gold has been used for a variety of ailments including for the treatment of Rheumatoid Arthritis [Richards et al., 2001]. The conventional oral dose is more than 1 mg/Day in terms of Gold. Colloidal Gold has been used at a much highe dose of 30 mg / Day as it is believed to be non-toxic.
More recently, role of solids in the form of nanoparticles ( particles smaller than 0.3 microns and more commonly smaller than 0.1 micron) is being established as catalysts for the promotion and inhibition of a variety of biological functions in humans, plants and in other unicellular organisms. The processes for the preparation of such solids are also quite complex/These nanoparticle based colloids compositions are are available (Purest Colloids, 2005)as suspensions or dispersions in mainly aqueous medium.
More recent literature on Gold, Silver, Copper and Zinc colloids
describes a wide range of human therapeutic properties for these materials [Purest
Colloids, 2005]. These colloids have metal particles as nanoparticlers. The typical
metal content and minimum suggested adult doses are given below:
Table 1 Dosage of metals for Metal Colloids
Metal Concentration Minimum Minimum
Daily Dose Daily Metal Dose
PPM ml microgm/day
Au 10 15-60 150-600
Ag 20 15 300
Zn 30 60 1800
Even for highly toxic materials such as Mercuric Chloride, Arsenic, and Lead the US EPA allowable Chronic Oral Reference dose is 21, 21 and 4 microgm/Day (Richrds et al., 2002).
Once the bottle is opened, the aqueous colloidal compostions from non-metals such as Zinc, Copper, have a limited shelf life[purest Colloids, 2005] of just a month as the metal nanoparticles get oxidized.
Relatively little is known about the usefulness of colloidal or nanoparticle solids compositions m veterinary applications.
Impact of nanoparticles on plant life is now being investigated [United press international, 2005]. Watt and his colleagues at the New Jersey Institute of Technology, U.S.A., have found that high doses of nanoparticles of Aluminium Oxide can stunt root growth in plants. However, they found Silicon Dioxide nanoparticles to promote root growth. A U.S. Patent application [Choi, 2005] claims that an aqueous liquid composition containing Titanium Dioxide nanoparticles and other adjuvants for plant frowth allows plant yields to be increased by increasing the photosynthetic efficiency of plants.
The present invention provides a novel, and a much simpler general method for the direct production of a wide range of novel new oil compositions containing colloidal and nanoparticulate solids along with or without other oil solubles formed from the starting solids and biomass. The range of oil compositions can be further extended by innovative compounding of such oil compositions with or without the addition of adjuvants, diluents, carriers, absoption and emulsification aids and converting these oils into a variety of ready to use dosage forms as desired. Oil compositions of this invention have a very high potency and therefore require a substantially lower daily dose for human consumption and for applications in agriculture and in other areas of life sciences when compared to available conventional compositions of the same solids and biomaterials. This reduces long term accumulation toxicity concerns considerably. Compositions also extend the practical usefulness range to all life science segments beyond human, veterinary and agriculture and also work as biocatalysts in biotechnology applications.
BRIEF SUMMARY OF THE INVENTION
This invention relates to compositions comprising oil extracts from solids in oils and fats to be used in human, veterinary, agricultural, marine , mycological and microbial applications.
The novel compositions in oil or fat are prepared from solids by taking the solids as such in dry form or their suspensions in water or other low boiling
solvents, with or without additional biomass homogenate, decoction or juice, combining them with oil or fat, adding water, heating or bringing the mixture to boil, maintaining the temperature of the mixture below the smoke point of oil or fat used, stirring the mixture to provide good contact of solids and biomass with all other phases present such as water, other low boiling medium , oil and the rising vapors and bubbles, driving off the water and other low boiling medium substantially to have a mixture of solids and biomass residue in oil phase, cooling the mixture, and filtering the mixture to substantially separate the oil phase from the biomass residue and solids particles > 1 micron in size , to obtain an oil phase referred to as the oil composition and an oily, wet residue of filtered solids and biomass. The filtered oil phase containing particles less than I micron along with other oil solubles from the starting materials and also formed during the heating and boiling process is the desired oil composition .
More novel compositions can be produced by combining in innovative ways a number of such oil compositions together along with known adjuvants, diluents and additioves for promoting ease of absorption and for creating targeted compositionsfor a particular application in a desired dosage form and dose content.
These compositions can be used to treat a wide variety of human, veterinary and crop health and disease aspects, both preventive and curative, encompassing a wide range of resistence, healthy growth, repair, restoration and anti-ageing issues. Thse compositions also have manifold applications in other areas of biotechnology. The dose level, in terms of the solids and biomass content of the oil compositons, required for producing useful effects is exceptionally low compared to conventional compostions from the same substances. These uses will become apparent as the various embodiments of the invention are discussed.
The novel oil composition of the invention is prepared by a method described below. The solids are taken in a container as pieces, crushed, in powder form or as foils, wires, sheets, suspensions/dispersions in water or other low boiling solvents such as alcohol or water/alcohol mixture and mixtures thereof
along with, optionally, a homogenate of biomass or its parts along with , optionally, additional water, or juice or decoction of the biomass. The biomass source can be of a plant or non-plant origin and may contain one or more of the whole biomass or parts thereof, optionally with additional decoction or juice of the said biomass.
When biomass homogenate is to be used, biomass or its part is first reduced in size by soaking, pounding and cutting, and dry or wet grinding by the addition of water as required, to produce a homogenate. The total biomass homogenate i.e. kala is filtered to separate the juice or liquid fraction (J) from the stem/leaf/plant parts or other biomass part residue (LR). The total homogenate (J and LR fractions ) may then be added or the two fractions may be added separately (mixed in any proportion). Optionally, additional juice of the biomass or its decoction may also be added to the homogenate i.e. kalka..
The solids with or without a biomass source as described in the above two paragraphs are then taken in a container and are then combined with water and oil and then heated or brought to boil maintaining temperatures below the smoke point of the oil. The water and any other lower boiling solvent are then substantially removed by boiling or evaporation with or witout the use of vaccum. The initial part of the cooking and boling process is normally carried out at atmospheric pressure. However, super-atmosphric pressure as in a pressure-cooker or a pressure vessel can also be used, if desired. The normal boiling time i.e the boiling time at atmospheric or super-atmospheric pressure is kept to less than 6 hours and normally the substantial removel of water and other low boiling sovents is also done within this 6 hour period. Constraining the time to less than 6 hours is necessary to prevent excessive ixidative and thermal degradation and loss of activity.
However, in another embodiment of the process, after subjecting the solids/water/biomass source mixture to less than 6 hours under normal boiling conditions, high vaccum may be applied to substantially lower the boiling point and the rest of the water/solvent can be removed under these conditions. Optionally, a slow bleed of an inert gas such as nitrogen may also be provided
during boiling to minimize exposure of the contents to oxygen at elevaterd temperatures when oxidative to minimize oxidative degradation.
Stirring is provided throughout to promote good contact between all the phases - solid, biomass, oil, water and other medium, vapors and rising bubbles. At the end of substantial removal of water and any other low boling medium, the entire mass is cooled, and then filtered to separate an oil phase substantially free of particles larger than 1 micron in size from the combined rsidue of solids and biomass.
Thus, the oil phase so separated is an oil composition of solids mainly smaller than 1 micron which remain suspended in the oil medium along with any other oil solubles and extractibles derived from starting solids and biomass. The salient features of this invention is:
- A simple method to directly prepare an oil phase composition from
solids and biomass sources containing particles smaller than 1 micron and other oil
solubles derived from solids and biomass and their reaction products
- The compositions of the invention have a wide range of useful
and unexpectedly useful results, along with high potency, low toxicity, and an
exceptionally long shelf life.
This invention also incorporates a novel feature as an "Extraction Concept." Traditionally, plants are typically extracted in one or more solvents. Use of oil for extraction of plants is described in Sharangdharsamhita for the production of Siddhataila.
However, the concept of using a water/oil medium to extract solids with or witout biomass for producing high activity oil compositions substantially free of > 1 micron particles but containing a suspension of The key features, and the 'Extraction Concept' outlined above are also applicable to making oil compositions simultaneously using one or more solids along with one or more plant or non-plant biomass source materials.
A number of such oil compositions can be combined in a creative manner to make a composition tailored to meet specific use requirement of dosage and delievery.
Potency - Individual Solids Exracts
That these oil compostions containing solids Daily oral dose based on total metal content of the oil compositions below 10 microgram per day [ for Zinc] and as low as 0.1 microgram per day [ for Gold and Silver and Copper] produce significant therapeutic effects in Humans. In case of Gold and Silver, this dose is more than 1000 times lower than the the minimum dose requirement of several hundred micrograms per day of current colloidal nanoparticulate metal products as shown in Table I.
Significant effects at extremely low dose are also found in cell culture experiments.
Crop application doses of solids are also extremely low at Starting with the indiviual novel oil compositions from a single solid , a wide range of high potency combinations can be made in a variety of ways.
Thus, several solids may be used simultaneously to make a combination extract. As an example, gold and silver may be used together to produce an oil composition containing both metals .
An extract of solids along with other biomass can also be made as a combined extract. Thus, Kalanchoe pinnata or Aloe leaves can be extracted
together with Zinc and Silver to create a combination with superior healing and anti-infective properties.
A number of indiviual oil compositions may also be combined along with diluents, adjuvants and other additives in any desired proportion to create novel compositions for specific applications.
Colloidal aqueous products containing Zinc ro Copper have limited shelf life due to the oxidation of the metals. It is recommended ( Pure Colloids, 2006) to consume these colloids within 4 weeks of opening the bottle. However, oil compositions made from Zinc and Copper prepared as per this invention remain stable and active even after 4 months after opening the bottle.
Embodiment A. Human
Oil compositions of this invention can be made from a variety of solids with or without the addition of other biomass. For each solid, at least some of the key biological activities as reported in the literature for its colloidal nanooparticulate product and for its Bhasma as per Ayurveda do get incorporated in the compositions of this invention. Hence, the compostions of this invention have a wide variety of human embodiments.
The daily solids dosages, however, are unexpectedly low- lower at least by a factor of 100 and often by a factor of 1000 or more - compared to the those for traditional products and for other modern colloidal products in similar applications.
Utility of the compositions of this invention are not limited to the embodimens directly taken from Ayurveda or the modern nanoparticle literature. Innumerable other embodiments for a particular human application are possible by combining solids and biomass in preparing the oil compositions and by innovatively combining such oil compositions to tailor make a composition with a desired use. B. Veterinary
Compositions of this invention may also be used to promote the health and productivity of livestock and poultry and other birds and to provide them with protection against infections and prmotion of general health.
Similar applications are also expected in case of marine organisms.
Utility of these compositions extends to all areas of plant kingdom. Beneficial effects are expected on vegetables, ornamentals, flowers, fruit, trees, cereals, legumes, herbs and medicinal plants. Beneficial effects include all aspects of plant life including promotion of resistance to pests and environment, promotion of plant growth, increase in productive plant life, regulation of secondary metabolite production, higher yield of desired produce, improved quality of produce and longer shelf life of produce.
D. Public Health
Utility of these compositions extends to pest control applications of interest to Public Health. Many embodiments are possible for the control of rodents and insects .
Utility of these compositions extends to microbial and mycological applications.
Certain oil compositions by themselves or along with other substances are useful for their anti-biotic activity or as activity enhancers on a variety of single cell organisms including bacteria, fungi, and parasites. Other oil compositions, when added to media in biological reactors and fermentors are useful as biocatalysts for the promotion of the biomass and for the ergulation of the expression of enzymes and other secondary metabolites by the biomass. IT Definitions Extract
Extracts comprise those preparations that involve the use of a solvent. Water , an oil or an organic compound may be solvents. Extracts, in the context of this invention may be made from one or more solids along with or without one or more biomass sources. The process of extraction involves heating and boiling with
vigorous stirring. This may, in general, lead lo both physical changes and chemical reactions. Thus, such a process may bring out some extraclibles which are soluble materials derived from the solids or biomass into the solvent phase. The process of extraction also bring out very finely suspended particles - in the colloidal range and also the even smaller nanoparticle range ( When oils are used as a solvent, generally all oils that are appropriate for the application can be used. Thus, a variety of natural oils and fats from any biomass may be used for the preparation of oil compositons of this invention. This includes any of the vegetable oils such as Coconut, Sesame, Olive , Almond, Orignaum (thyme), Tea Tree, Wheat Germ, Neem (Azadirachta indica), Karanj (Pongamia glabra) and animal (lard, fish, and butterfat from milk from various species), and those produced by the extraction industries (mineral, immersion and halocarbon). Purified oil components (lipids) and synthetic oils (such as fatty acid triglycerides or esters) may also be used. While all combinations of such oils and fats can be used, it is preferred to avoid those oils and oil combinations that polymerize extensively or form gum during the preparation procedure that would interfere with extraction and subsequent filtration and processing.
Both solids and biomass sources are used as inputs in the method of preparing oil compositions of this invention. A "solid" used as an input raw material in the context of this invention are those which are insoluble (e.g. metals) or only sparingly soluble (e.g. minerals, and salts or high polymers) in the final oil phase and are therefore capable of generating extremely small particles which will remain suspended in the final oil composition. Any other starting material of a cellular i.e biological origin will be considered as a biomass source.
An extract of solids may be made from any type of solids including metals, non-metals, semi-conductors, insulators, minerals, gems. Both organic
and inorganic solids may be used. Solids may be in the form of pieces, sheets, foils, wires, powders or may be as a paste, suspension or dispersion in a medium. The medium for dispersion may be water, other sovents ( such as alcohol or others with a boling point lower than water) or mixtures thereof.
Biomass used may be of plant or non-plant origin and may contain any part or the entire biomass. Plant biomass sources include plant parts such as leaves, stems, flowers, inflorescences, shoots, cotyledons, etc. Non-plant biomass parts include milk, organ meat, blood, fruiting bodies, mycelium, hair, horn etc. The various parts may be dehydrated or used fresh.
The term " extract" in the context of the current invention refers to any extract, made from a solid with or without plant or non-plant biomass, that has at least one activity of the solid and the biomass. An extract activity is one that is evident throughout the description of the invention.
III. Using the invention
The following describes the preparation of extract from a variety of solids with or witout the simultaneous addition of bomass. Al: Extracts from Solids:
The following describes the preparation of an extract prepared from Gold. Also see other Examples. It will be apparent to one of skilled in the art that many variations of the following procedure may yield extracts with similar activities. In general, any extract produced from Gold or from any other solid containing Gold as one of the constituents with or without the addition of biomass that has at least one of the activities of the the form of Gold used as raw material (see examples) is contemplated by the inventors.
However, such a procedure can be used to prepare oil compositions from a wide variety of other solids from metals, non-metals, semi-conductors, insulators and mixtures thereof..
A 1 gm piece of 24 carat gold was taken in a container along with 500 ml water and 500 ml sesame oil. The mixture was brought to boil with continuous stirring and boling continued at low heat to drive off water. Continuous
stirring was provided to enable intimate contaxct of the piece with the mixture of water, sesame oil and rising bubbles. When substantially all the water was removed as indicated by the almost complete cessation of bubbling , the heating was turned off. The mixture was allowed to cool. The piece of gold was removed from the oil phase . In this case, there were no other visible solids or turbidity in the oil phase indicating that solids >l micron were substantially removed. The oil phase is the desired oil composiion and is an extract of Gold including gold nanoparticles.
A2: Extraction from solids together with a Biomass.:
The following describes the preparation of an extract prepared from Copper foil as the metal and Aloe as the biomass. It will be apparent to one of skill in the art that many variations of the following procedure may yield extracts with similar activities. .
However, any extract can be similarly prepared from any other solid or mixtures thereof with or without the addition of biomass that has at least one of the activities of raw materials used (see examples) is contemplated by the inventors.
500 gm Aloe leaf is taken in a blender and blended by the addition of 500 ml water into a homogenate. This Aloe homogenate is taken along with a 5 gm thin foil of copper into a container. 1000 ml of Sesame oil is added and the mixture and the entire contents are brought to boil, with continuous stirring. Boling is continued at low heat to drive off water. Continuous stirring was provided to enable intimate contaxct of the copper foil with the mixture of water, aloe homogenate and sesame oil. When substantially all the water was removed as indicated by the almost complete cessation of bubbling , the heating was turned off. The mixture was allowed to cool and filtered over cheesecloth to substantially separate and remove large particles of biomass and the copper foil from the oil phase. The oil phase is the desired extract and the oil composiion of interest.
In both of above general procedures, several variables can be adjusted to achieve extracts of desired potency. For example, the starting solid material may consist of pieces, foils, sheets, wires, powder, granules, and pastes or
suspensions in water or any other medium with a boliling point below that of water. Biomass homogenate may be from leaves, stems, shoots, seeds, bark, rhizome or the entire plant. Alternatively, juice that has been manually extracted, or expressed, from the plant or plant parts or a decoction of plant or plant parts may also be used. Pounding can be done in a mortar or with any other device that can reduce the size of the starting material. Instead of a blender to homogenize the plant tissues, a mortar and pestle, or any other device or method that can destroy the integrity of the plant tissue, may be used.
Heating can be provided to the preparaion vessel by a direct flame or by condensing vapors in a jacket or by passing hot gasses in a jacket surrounding the container. Heating may also be provided using microwave radiation. Heating may be done at atmospheric pressure or super-atmosphric pressure as in a pressure-cooker or a pressure vessel. It is important to restrict the total time of heating and boiling at these pressures to less than 6 hours to ensure that excessive oxidative and thermal degradaion leading to a loss of activity and build-up of toxicity does not take place.
Usually, substantial removel of water and other low boiling solvent is achieved during this atmpspheric/super-atmosphric heating period. However, after such an initial heating/ boiling period, further processing may be done, if required, at a lower temperature under vaccum to remove substantially all of remaining water and any other low boiling solvent.
It is apparent to one of skill in the art to adjust other variables as appropriate, as, for example, when large-scale preparations are desired.
The compositions thus made may also be further compounded with other oil ompositions and dluents, carriers and adjuvants to achieve ready-to-use compositions of different strengths that are suitable for various applications. Dilution serves important functions, including reducing any irritants and providing convenient doses. General penetrants and absorption aides such as Isopropyl myristate or MCT (Medium Chain Tryglyceride fraction) oil may be admixed. A wider range of compositions may be made by compounding together a number of such oil extracts
B. Pharmaceutical compositions
The compositions of the invention can be incorporated into pharmaceutical compositions. Such compositions typically comprise the solids extracts of the invention along with or witout biomass or mixtures thereof
A "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Liposomes and non-aqueous vehicles such as fixed oils may also be used. Except when a conventional media or agent is incompatible with an active compound, use of these compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.
The pharmaceutical compositions for the administration of the active compounds, such as those of any of the plant extracts, may conveniently be presented in dosage unit form and may be prepared by any of the methods well known in the art of pharmacy.
A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration, including intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal and rectal administration. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.
Pharmaceutical compositions suitable for injection include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. Such compositions should be stable during manufacture and storage and must be preserved against contamination from microorganisms such as bacteria and fungi. Various antibacterial and antifungal agents can be included in the composition. Compositions that can delay absorption include agents such as aluminum monostearate and gelatin.
The oil compsisitons themselves, suitably diluted can be dispensed with a dropper bottle for oral administration. Other forms of oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets.
Compositions for inhalation
For administration by inhalation, the compounds are delivered as an aerosol spray from a nebulizer or a pressurized container that contains a suitable propellant, e.g., a gas such as carbon dioxide.
Systemic administration, including patches
Systemic administration can also be transmucosal or transdermal. For transmucosal or transdermal administration, penetrants that can permeate the target barrier(s) are selected. Transmucosal penetrants include: detergents, bile salts, and fusidic acid derivatives. Nasal sprays or suppositories can be used for transmucosal administration. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams.
Creams are useful for a variety of external applications such as on chapped lips, cracked feet, heat rash, face cream, pimples, hand and body lotion to restore darkened skin after sun exposure, etc.
The compounds can also be prepared in the form of suppositories (e.g., with bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.
In one embodiment, plant extracts are prepared with carriers that protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Such materials can be obtained commercially from ALZA Corporation (Mountain View, CA) and NOVA Pharmaceuticals, Inc. (Lake Elsinore, CA), or prepared by one of skill in the art. Liposomal suspensions can
also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art.
In the treatment of human conditions which require the solids containing compositions of the invention, an appropriate solids dosage level will generally be about 0.001 to I microgm per kg patient body weight per day which can be administered in single or multiple doses. Preferably, the dosage level will be about 0.001 to about 0.1 microgm/kg per day. The copositions may be administered I to 4 times a day.
For topical applications, the composition may have a solids content of about 0.1 ppm to 100 ppm, more preferably 0. 3 ppm to 30 ppm.delivering 0.01 microgm to l0 microgmper application. The compositions may be administered 1 to 8 times per day. preferably once or twice per day. Alternatively, pads and other materials may be impregnated with such compositions and held in contact to the surface of the subject for chronic application.
The dosages outlined above are also suitable for veterinary applications. It will be understood, however, that the specific dose level and frequency of dosage for any particular subject may be varied and will depend upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age. body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition, and the host undergoing therapy. In addition, the site of delivery will also impact dosage and frequency. Also understood, however, is that dosage for livestock may also differ. A skilled artisan will know how to adjust the unit dosage.
Dosage of oil compositions of this invention in the baits used for pest control application may be 0.01 to 1%.
The composition of the invention, such as solids or solids/biomass extracts, may be delivered to the interstitial space of tissues of the animal body by injection into the tissues comprising these cells. They are preferably delivered to sites of injury, preferably to live cells and extracellular matrices directly adjacent to dead and dying tissue.
Any apparatus known to the skilled artisan in the medical arts may be used to deliver the compositions of the invention to the site of injury interstitially. These include, but are not limited to. syringes, stents and catheters.
Any apparatus known to the skilled artisan in the medical arts may be used to deliver the compositions of the invention to the circulation system. These include, but are*not limited to, syringes, stents and catheters. One convenient method is delivery via intravenous drip. Another approach would comprise implants, such as transdermal patches, that deliver the compositions of the invention over prolonged periods of time. Such implants may or may not be absorbed by the subject over time.
The compositions of the invention may be delivered in a way that is appropriate for the surgery, including by bathing the area under surgery, implantable drug delivery systems, and matrices (absorbed by the body over time) impregnated with the compositions of the invention.
Direct application of the compositions of the invention, such as plant extracts, may be used. For example, gauze impregnated with plant extracts or active components may be directly applied to the site of damage, and may be held in place, such as by a bandage or other wrapping. Alternatively, the compositions of the invention may be applied in salves, creams, or other pharmaceutical compositions known in the art meant for topical application.
Baits for Household Pest Control
Oil compositions may be compounded with other adjuvants to prepare solid baits for use in rodent and insect control.
C. Agricultural/horticultural compositions
Compositions suitable for application to plants
In its simplest form, the extract compositions that are suitable for agricultural compositions are simply diluted in water. Oil, powder and tablets of the extract compositions may be used.
It is also possible to prepare combinations with other pesticidally active substances, fertilizers and/or growth regulators, for example in the form of a ready mix or a tank mix. These can be thought of as to be "carriers" for the plant extracts.
Wettable powders are preparations which are uniformly dispersible in water and which, besides the active substance, also comprise ionic and/or nonionic surfactants (wetting agents, dispersants).
Emulsifiable concentrates are prepared by dissolving the extracts in an organic solvent, for example butanol, cyclohexanone, dimethylformamide, xylene, or else higher-boiling aromatics or hydrocarbons, or mixtures of the organic solvents with the addition of one or more ionic and/or nonionic surfactants (emulsifiers)
Dusts are obtained by grinding or mixing the plant extracts with finely distributed solid substances, for example, talc, natural clays such as kaolin, bentonite and pyrophyllite, or diatomaceous earth.
Suspension concentrates can be water-based or oil-based. They can be prepared, for example, by wet grinding using commercially available bead mills with or without an addition of surfactants, for example those that have already been mentioned above in the case of the other formulation types.
Emulsions, for example oil-in-water emulsions (EW), can be prepared, for example, by means of stirrers, colloid mills and/or static mixers using aqueous organic solvents in the presence or absence of surfactants, for example, in the case of the other formulation types.
Granules can be prepared either by spraying the active substance onto adsorptive, granulated inert material or by applying active substance
concentrates to the surface of carriers such as sand, kaolinites or granulated inert material with the aid of binders, for example polyvinyl alcohol, sodium polyacrylatc or else mineral oils. Suitable active substances can also be granulated in the manner that is conventional for the preparation of fertilizer granules, if desired as a mixture with fertilizers.
The rate of application of an active solids extract on the basis of the solids content is is 0.01 to 100 mg per hectare per year, applied in 4 to 20 sprays per year (or 2- 6 sprays per season). More preferably, 0.1 to 10 mg solids per hectare per year are applied. For herbicidal effects or for control of excessive growth , the solids dosage per hectare per year may be increased 10 to 1000 fold..
Components that can also be present in the metal and biomass oil extract compositions suitable for plant (agricultural) application, include fertilizers or pesticides, natural enzymes, growth hormones such as the gibberellins (gibberellic acid and gibberellin plant growth hormones), and control agents including pesticides such as acaracides and molluskicides, insecticides, fungicides, nematocides, and the like, depending of course on their compatibility with particular extracts.
The solids and biomass extract compositions suitable for plant application can be in oil form, solid form or in the form of an aqueous dispersions.
Particular extract combinations may be added to herbicides, known
in the art, to increase their effectiveness; as such, these solids extracts can also be
used to control unwanted proliferation of weeds and other vegetative growth.
D. Public Health Applications
Oil compositions may be added as a component in the preparation of standard baits for the control of rodents and other insects. In the simplest embodiment, 0.1% to 1% of thee extract may be added during bait preparation.
E. Mycological and Microbial Applications
Compositions suitable as Promoters of Biocatalyic Agents
In its simplest form, the extract compositions that are suitable for promoting the activity of mycological [ yeast, fungus] or microbial agents are the oil compositions themselves which may be added to the media in fermentors or
other reactor vessels carrying out a specific biological conversion using a mycological or microbial specie as a catalyst.
Compositions suitable as Antibiotic Applications Oil compositions containing solids may be used directly for applications for controlling or inhibiting the growth of bacteria, yeast and fungi. Thus, oil compositions may be added to drinking water to reduce the microbial/mycological contamination in potable water applications for humans, and in veterinary applications for cattle and birds.
The following examples are included to demonstrate preferred embodiments of the present invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments that are disclosed and still obtain a like or similar result without departing form the spirit and scope of the invention. For example, heating could be provided with steam or hot heat transfer medium to reduce degradation due to wall hot spots. Use of nitrogen or other inert gas blanketing may also be used to reduce degradation. After a period of boiling at atmospheric pressure, further removal of water could be done at a lower temperature under vaccum to reduce degadation. The extraction process can also be carried out in a continuous manner by using the well established engineering methods of continuously introducing biomass, oil and water at one end and continuously withdrawing the liquid slurry at the other end of a suitably designed vessel.
I. Examples of Solids Extraction
The following examples illustrate solids extraction with or without the simultaneous presence of biomass. However, one of skill in the art will know how to vary the various variables to obtain other such solids extracts and solids with biomass extracts of the invention.
In following examples of solids extraction and solids with biomass extraction, a wide range of the proportion of solids and biomass weight to final extract can be used and suitably designated as explained herein.
Solids for extraction may be in their natural form, processed for purification or fractionation or may be made synthetically by various processes.
Solids can be used in a variety of physical forms such as small pieces, foils, sheets, wires, powders and suspension of solids in water or other low boiling medium such as alcohol.
Solids used can also be both crystalline, amorphous, and glassy and may also contain several phases together as in alloys, minerals and in herbo-mineral products of Indian Traditional Medicine such as Bhasma..
Solids may be in the elemental form as noble metals [ such as Gold, Silver. Platinum] and their salts, non-noble metals [such as Zinc, Iron, Copper, Tin, Lead] and their salts, and other elements such as Mercury.
Solids amy be in the form of derivatives such as oxides[ such as Alumina. Zinc Oxide, Sillica, Titania], sulphides, carbonates, sulphates[ such as Calcium and Barium carbonates and sulphates].
Solids may be alloys, other natural forms [ Animal antlers/ horns, Elephant tuskars, Cock's Cob ], Minerals [ such as Coral, Sea Shells, Bauxite, Pyrites, Orpiment], Gems [such as Diamond, Pearl, Ruby ] and Herbo-mineral products of Indian Trakitional Medicine such as Bhasma [Sudarshan, 2005].
Solids may be organic such as Diamond and Graphite, and in the form of inorganic and organic polymers.
If solids are being used which when added may casue a violent reaction or release of toxic materials, appropriate precautions must be taken to ensure safety of the operation and the workers and the containment of hazard.
Solids or their mixtures which may polymerize during processing or form a sticky mass or cause an uncontrolled reaction and thus ender subsequent
recovery of the oil phase as the extract difficulty or impossible, should not be
Example I General solids extraction procedure
A pieces of silver coin with a total weight of 15 gm was added to a container along with 500 ml water and 900 gm of sesame oil. The mixture was brought to boil and the water was driven off with stirring in 70 minutes as indicated by a cessation of bubbling. The oil extract containing silver coin was cooled, the silver coin was removed.The oil phase left ebhind was analyzed for silver content to have 1 ppm silver. This Metal oil extract was designated as AgOL - 1 .
The procedure can also be applied to solids in other forms such as strips, sheets, foils, wires, etc.
Example 2 Processing of Powdered Solids 2 gms of Zinc Oxide powder was taken in a container and mixed with 1000 ml of water and 2000 gm of sesame oil. The mixture was heated and brought to boil. Water was stradily removed over moderate heat with continuous stirring. Substantial removal of water was indicated by a near stoppage of bubbling at the end of 105 minutes. The oil phase containing ZnO powder was cooled and filtered over cheesecloth to substantially remove all large ZnO particles. The oil filtrate is the ZnO Oil extact. This was analyzed for total Zn at 20 PPM and designated as ZnO OL-20.
This procedure can be applied to a variety of other solids in powder form such as Bhasma, crushed mineral powders, powders of other metals and their salts, powders of natural products such as Horns, etc.
Example 3 Processing of a Mixture of Solids Five 1 gm pieces of gold ( 24 carat) an one 15 gm gold coin (99.9% purity) wee taken together in a container with 500 ml water and 2000 gm sesame oil. The mixture was brought to boil with stirring. Boiling with stirring was continued for 120 minutes when the bubbling nearly ceased indicating substantially complete removal of water. The oil phase containing pieces of gold and silver was cooled,
the pieces were removed and the resultant oil extract was analyzed to have 1 PPM of both gold and silver. This oil extract was designated as Au/Ag OL -1.0/1.0
Any number of solids can be mixed together in a variety of physical forms as per the example above provided they do not lead to undesirable results stipulated in the rpeamble to the section. The same can be said for the simultaneous processing of combinations of solids and biomass to create final oil extracts tailored to specific use. Those combinations which cause a violent uncontrolled reaction, pasty or polymeric mass which renders subsequent recovery of oil extract very difficult or impossible may not be used as per the examples described herein.
Example 4 Solids with Biomass: A mixture of small,
medium and large leaves (1205 g) of Kalanchoepinnata (Lam.) pers. was harvested. The leaves were washed with water, and blended in a household blender by addition of water, approximately half the weight of plant material, 600 g (or 600 ml). Separately, an equal weight of sesame oil was heated in a stainless steel pot. Five 1 gm pieces of Gold were also added. The blended mixture of leaves and water was charged to the pot containing sesame oil and gold pieces and boiled for about 2 hours and 45 minutes until a very fine foam appeared indicating substantially a complete removal of water. Heating was stopped, the mixture cooled and filtered through a once-folded (double) layer of cheesecloth to separate the first extract from leafy residue containing metal pieces. The leafy residue containing gold pieces was stirred with sesame oil equal to half the weight of the wet residue and filtered through a double layer of cheesecloth to obtain a second extract. The two extracts were combined and sesame oil was added to adjust the total weight of the final extract to 1205 g. This composition is based on 100 g of leaf equivalent per 100 g of total extract. This final extract was also analyzed for gold and was found to contain 0.5 PPM gold. The final extract was named R/Au-100/0.5.
This procedure can be used for various combinations of solids and biomass to create final oil extracts tailored to specific use. Those combinations
which cause a violent uncontrolled reaction, pasty or polynmeric mass which renders subsequent recovery of oil extract very difficult or impossible may not be used.
Using Multiple Biomass Sources with Solids
This is a general procedure for directly making Multi-solids, multi-biomass compostions tailored for specific applications.
This procedure can be used for various combinations of solids and biomass to create final oil extracts tailored to specific use. Those combinations which cause a violent uncontrolled reaction, pasty or polynmeric mass which renders subsequent recovery of oil extract very difficult or impossible may not be used.
Example 5 General procedure for Multi-component Compositions
150 gm of washed Kalanchoe pinnata (Lam.) pers. Leaves, 50 g of washed Aloe vera.Linn. leaves , 30 gm powder of Phyllanthus emblica fruit, 15 gm powder of Terminal is chebula seeds and 5 gm powder of Terminalia bellerica fruit rind were blended in a household blender by addition of 500 ml water to produce a total homogenate. This homogenate, along with a 20 gm sheet of Zinc and a 15 gm piece of silver were charged to one of the pots containing 800 g of sesame oil and the mixture was boiled with stirring for 95 minutes until a fine foam formed and subsided. This indicates substantially removal of all the water. The oil phase containing biomass residue and metal pieces was cooled and filtered through double layer of cheesecloth to separate the first oil extract. The residuecontaining metal pieces was stirred with an equal weight of sesame oil. The two extracts were combined and additional sesame oil was added to a final total weight of 1200 g. This fonal composition was analyzed for Zn and Ag content was found to have 10 ppm Zn and 0.5 ppm silver. This 1200 gm final composition from an initial 300 g of biomass and containing Zn and Ag was named Wound/Zn/Ag-25/10/0.5.
Using Suspension of solids This is a general procedure for making extracts from suspension of solids when the suspension may be in water and/or in a low boiling solvent.
Example 6 General procedure for suspension of solids 50 ml of a nanoparticle suspension in water containing 100 ppm gold was mixed with an additional 200 ml water and 500 ml Sesame Oil. The mixture was heated and brought to boil. Water was slowly removed over moderate heat with continuous stirring. Substantial removal of water was indicated by a near stoppage of bubbling at the end of 105 minutes. The oil phase containing containing gold nanoparticles was cooled. The oil phase is the Gold Oil extact. This was analyzed for total Au at 11 PPM and designated as AU OL-11.
In all of these extract preparations, stirring was provided while boiling the mixture of solids/biomass/water and oil.
Extracts by using the general procedures outlined in Examples 1 to 6 can also be made from all other solids, with or without biomass sources and their combinations.
II. Useful Compositions of Solids and Solids/Biomass Extracts
The following examples illustrate compositions of solids and solids with biomass oil compositions for a variety of applications; however, they are not meant to be limiting. The same principles and methods can be used to prepare useful compositions from any Solids with or without the simultaneous presence of biomass. It will be apparent to one of skill in the art how to modify the various preparations for specific applications.
Compounding the extracts with diluents, Carriers, and other adjuvents is not just a process of mere admixture. Such compounding is both desirable and useful to tailor-make new and more effective compositions specifically suited for a particular use. Such compounded compositions can effectively change the rate of release of the solid/biomass actives, and can increase the efficacy/toxicity ratio for the particular application. Compounding can also change the stability of the extracts. This is illustrated with a few examples.
Example 7 Dilution for Composition Eflicacy Enhancement Extracts made by the general procedure described in Examples I -6 were further diluted with sesame oil to make extracts of different strengths. For example, the 1200 gm final extract of example 5 made from 300 gm of a mixture of starting biomass and zinc and silver was designated as Wound/Zn/Ag- 25/10/0.5. This extract was diluted by mixing one part of this oil extract with 1.5 parts of Sesame oil and the diluted extract was named Wound/Zn/Ag- 10/4/0.2. Similarly, one can make diluted oil extracts of any desired strength such as convenient and stable dosage forms.
The Wound-10/Zn/Ag - 10/4/0.2 is more suitable to be given orally. However, more sensitive skin application and skin lotions require a much lower concentration.
Similar oil dilution are necessary to tailor-make oil compositions for direct use at th root zone fo a plant.
Example 8 Solids extracts with pharmaceutical carriers Extract made by the general procedure described in Example above is further compounded with carriers such as sucrose, lactose, or other sugars. Alternatively,the oil extrat can be absorbed on porous supports such as precipitated calcium carbonate, talc, precipitated silica, etc. Powders can be made by mixing one part of the extract with with the required parts of carrier solids. Thus, one can make these diluted powders of any desired strength as convenient and stable dosage forms.
Example 9 Tablet compounding
Tablets of different strength can be made as convenient and stable dosage forms for a variety of applications. A few typical recipes for tablet making are given in the examples below. However, a variety of other excipients may also be used, with or without other adjuvants, for tablet making.
150 mg tablets
100 g of ZnOL-20 was mixed with 900 g sucrose and homogenized in a pestle and mortar to make a diluted powder designated as
ZnOL-2(P). This was then mixed with other components, processing aids and binding agents in the proportion of I kg ZnOL-2(P), 0.3 kg gum Arabic, 0.3 kg gelatine, 1.15 kg magnesium stearate, 0.3 kg talc, and I 1.95 kg sucrose (for a total of 15 kg) and made into tablets weighing 150 mg in a tablet making machine.
250 mg tablets
100 g of AuOL-1 is mixed with 900 g sucrose and homogenized in a pestle and mortar to make AuOL-0.1 (P). This was then mixed with other components, processing aids and binding agents in the proportion of 1.0 kg AuOL-0.1 (P), 0.1 kg gum Arabic, 0.1 kg gelatine, 0.35 kg magnesium stearate, 0.1 kg talc, and 3.35 kg potassium chloride (for a total of 5.0 kg) and made into tablets weighing 250 mg in a standard tablet making machine.
Example 10 Cream formulations
The notations to describe the strength of oil, powder and tablet in terms of leaf equivalent are also applicable to creams.
All purpose cream
Two mixtures were prepared. Mixture A consisted of 3% stearic acid, 40% mineral oil (70 viscosity), 7% lanolin, 10% petrolatum (USP), 2% cetyl alcohol, 2% microcrystalline wax and 1% Wound/Zn/Ag-25/10/0.5. Mixture B consisted of 5% MgAl silicate (as a 5% dispersion), 1.78% triethanoloamine, and 28.22% water.
Mixtures A and B were heated separately to 70°C. Mixture B was then added to mixture A and stirred continuously. Then, the mixtures was cooled to 35-40°C. A negligeable amount of fragrance (such as lavendar) and preservatives (such as parabens) was then added, and the mixture mixed until dispersion was complete. Evaporation loss was replaced with water.
Hand and body lotion (oil in water emulsion)
Two mixtures were prepared. Mixture A consisted of 2.5% stearic acid, 2% mineral oil (70 viscosity), 1% glyceryl monostearate, 2% isopropyl palmitate, 1% petrolatum (USP), 1% cetyl alcohol, 0.25% PEG 40 stearate wax and 1% Wound/Zn/Ag- 25/10/0.5. Mixture B consisted of 7% Carbomer 934 (as
a 2% dispersion), 5% glycerine, 1% triethanolamine (as 99% solution), and 76% dcionizcd water.
Mixtures A and B were heated separately to 70°C. Mixture B was then added to mixture A and then agitated. Then, the mixtures were mixed to 35°C. A negligible amount of lavender and parabens were added for fragrance and stability, respectively, and the mixture mixed until dispersion was complete.
Dated this 17th day of May, 2006.
Dr. Shantaram G. Kane Applicant and Inventor
The Controller of Patent, The Patent Office, Mumbai Branch, Mumbai 400 037
|Indian Patent Application Number||755/MUM/2006|
|PG Journal Number||37/2011|
|Date of Filing||17-May-2006|
|Name of Patentee||KANE SHANTARAM GOVIND|
|Applicant Address||1, INDRADHANUHSYA APTS., AGARKAR ROAD, 827/A SHIVAJI NAGAR, PUNE-411004,|
|PCT International Classification Number||A61K35/78|
|PCT International Application Number||N/A|
|PCT International Filing date|