JP2007254414A - Antitussive composition containing extract of plant of genus bidens - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an antitussive composition or cough prevention composition having low side action and effectively suppressing chronic cough and other cough reflex. <P>SOLUTION: High cough suppressing effect is found in an extract, especially hot water extract of a plant of the genus Bidens. Action to inhibit the intake of anandamide which is an endogenous substance of a capsaicin receptor or a capsaicin receptor antagonistic action is supposed to be involved in the action mechanism of the extract. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an antitussive or cough preventing composition comprising a Sendangusa plant extract as an active ingredient.

Cough is a series of defensive responses to rapidly increase intrathoracic pressure, resulting in a strong expiratory effort, resulting in the invasion of foreign bodies into the airways and the removal of airway retention secretions. It is. In such a cough reflex, a chronic cough (or refractory cough), in which the cough continues for at least 3 to 8 weeks, becomes a problem. For chronic cough, “cough caused by diseases and causes with normal cough receptor sensitivity” that accompany asthma, sinus bronchitis, chronic bronchitis, mycoplasma pneumonia, etc., atopy, gastroesophageal reflux, angiotensin converting enzyme Inhibitors, postnasal drip, laryngeal allergy, persistent cough after cold syndrome, “chronic cough due to disease or cause with increased cough receptor sensitivity” caused by non-asthmatic eosinophilic bronchitis, and psychogenic・ Has chronic cough due to illness or cause of unknown habitual or chronic interstitial pneumonia.
These chronic coughs are problematic in that the effectiveness of conventional central antitussive drugs is low, and there is a demand for the development of drugs that effectively treat these chronic coughs.
On the other hand, Sendangusa plants such as Bidence Pirosa are herbs that have been around for a long time, and decocted dried ground parts are used for drinking. It is expected to have various pharmacological activities, for example, it has been reported that the plant extract of the genus Sendanga contains an anti-inflammatory component (see, for example, Patent Document 1).

JP 2003-73315 A

  An object of the present invention is to provide an effective antitussive or cough preventing composition. Another object of the present invention is to provide a composition for treating or preventing chronic cough that cannot be effectively treated with conventional central antitussive drugs. Another object of the present invention is to provide a cough-preventing or cough-preventing composition having few side effects even when taken for a long time.

The present inventor has found that the extract of the plant belonging to the genus Sendanga has a strong antitussive effect or cough preventing effect, and has completed the present invention. That is, the present invention provides an antitussive or cough preventing composition containing a Sendangusa plant extract.
The antitussive composition of the present invention is particularly effective for chronic cough.
It is preferable that the extract of the plant of the genus Sendanga is a hot water extract. The Sendangusa plant is preferably a bidenspirosa.
Further, the antitussive or cough preventing composition of the present invention may be in the form of food.

  By administering the composition containing the Sendangusa plant extract of the present invention, the cough reflex in an animal can be significantly suppressed or prevented. The plant extract of Sendungusa significantly suppresses capsaicin-induced cough in ovalbumin-sensitized and non-sensitized mice, so that chronic cough due to diseases and causes with increased cough receptor sensitivity and normal cough sensitivity Chronic cough caused by disease or cause can be suppressed. The suppressive action mechanism of the Candela genus plant extract on cough reflex significantly suppresses anandamide-induced cough, which is an endogenous ligand of the capsaicin receptor (TRPV1 receptor) present in the cell membrane of the C fiber end. This is considered to be a direct inhibitory action on the anandamide transporter having a role of taking up a receptor or anandamide into cells. In other words, the sensitivity of the cough receptor is reduced by suppressing the excitement of the C fiber by anandamide transporter inhibition or direct inhibition of the TRPV1 receptor, and an inhibitory action on the cough reflex is expressed. Due to the sensitivity-reducing action of the cough receptor, it is effective for various chronic coughs, particularly for pathological coughs with increased cough sensitivity.

(Method for producing Sendangsa plant extract)
As described in Japanese Patent Application Laid-Open Nos. 2001-178390 and 2001-233727, the plants belonging to the genus Sendangsa used in the present invention are a group of plants referred to as genus Bidens in scientific name. There are many varieties because they cross each other in a wide variety, and there is confusion in botany, and it is extremely difficult to identify because the correspondence between scientific names, Japanese names, and Han names is also mixed. The Sendangsa plants used include the following:

Bidens pilosa L. (Kosendangusa, Koshirono Sendangusa, Sakai Toyokusa)
Bidens pilosa L. var. Minor (Blume) Sherff (Shirobanasendangusa, Shironosendangusa, Koshironosendangsa, Kosendangsa, Sengyogusa)
Bidens pilosa L. var. Bisetosa Ohtani et S. Suzuki
Bidens pilosa L. f. Decumbens Scherff (high millet snow Bidens)
Bidens pilosa L. var. Radiata Scherff (may also include Tachiawayukisendangusa, Hiawayukisendangusa)
Bidens pilosa L. var. Radiata Schultz Bipontinus (Shironosendangusa)
Bidens biternata Lour. Merrill et Sherff (Sendangsa)
Bidens bipinnata L. (Kobano Sendangsa, Sendangsa)
Bidens cernua L.
Bidens frondosa L. (American Sendangsa, Seitakatakogi)
Bidens maximowicziana Oett
Bidens parviflora Willd
Bidens radiata Thuill. Var. Pinnatifida ( Turcz.) Kitamura ( Ezonotaukogi)
Bidens tripartita L.

Among the above-mentioned plants belonging to the genus Sendangsa, Bidens pilosa is particularly preferable from the viewpoint of effects.
The use part of the above-mentioned Sendangsa plant may be any part of the root, the above-ground part (stem, leaf, flower, etc.) or the whole plant. In particular, the use of leaf and stem portions is preferred in terms of efficacy.
The Sendangsa plant may be used raw, but may be a dried product or a processed dried product. Usually, raw plants are dried in the sun or dried with hot air (for example, 70 to 80 ° C.), or steamed with steam, for example, for about 1 hour to 1 and a half hours, and then dried. Moreover, you may use the thing processed and dried by the method of Unexamined-Japanese-Patent No. 2001-178390.

Furthermore, you may use what was extracted by adding water or a hydrous solvent at normal temperature or under heating. As an extraction method, for example, it is possible to obtain an extract by immersing and standing, or using an extraction device such as a Soxhlet extractor.
Among the above-mentioned plants of the genus Sendangsa, Bidens pilosa is particularly preferable.
The above-mentioned Sendangsa plant usually uses a raw plant obtained by drying in the sun or hot air (for example, 70 to 80 ° C.), or steaming, for example, steaming for about 1 hour to 1 and a half hours, and then drying the plant. Also good.
The use part of the above-mentioned Sendangsa plant may be any part of the root, the above-ground part (stem, leaf, flower, etc.) or the whole plant. In particular, the use of leaf and stem portions is preferred in terms of efficacy.

  In addition, other components or plants may be added to the composition of the present invention for the purpose of correcting taste, fragrance, flavor, etc., improving extraction efficiency, and improving workability. Specific examples of other components or plants include cereals such as barley, spices such as ginger and turmeric, straw, and malt. When such a component or plant is added, it may be extracted by adding to the plant of the genus Sendangusa, or may be added after extraction. Such a component may be added in an amount of 1 to 50% by mass based on the dry weight with respect to the dry weight of the Sendangusa plant.

  One embodiment of the method for obtaining the extract of the plant belonging to the genus Sendanga contained in the composition of the present invention is as follows. As described above, the plant of the genus Sendangsa is dried or steamed with steam and dried. It is dried or steamed and then dried, and extracted by adding a solvent at room temperature or under heating. As an extraction method, for example, the extract can be obtained by immersing and standing, or using an extraction device such as a Soxhlet extractor.

Examples of solvents used for extraction include water, methanol, ethanol, propanol, butanol, ethylene glycol, propanediol, butanediol, glycerin and other alcohols, and their hydrates, acetone, ethyl methyl ketone, chloroform, Methylene chloride and ethyl acetate and their hydrates may be used. Moreover, the mixture containing 2 or more types of the said solvent may be sufficient. The amount of the solvent added can be, for example, about 1 L to 100 L with respect to 1 kg of the total dry weight of the plant to be used.
The temperature at the time of extraction can be normally performed at room temperature to about the boiling point. The extraction time depends on the temperature and the solvent, but when extraction is performed at room temperature to about boiling point, it can be performed over a range of about 1 to 300 hours.
The extraction is particularly preferably carried out with water, more preferably from room temperature to the boiling point, more preferably from 70 to 100 ° C, still more preferably from 80 to 100 ° C.

  The extract may be concentrated or solid (dry product) by distilling off the solvent if necessary. When used as a concentrate, it may be used as it is after the concentration is adjusted. Further, the extract may be used after being subjected to treatments such as activated carbon treatment, resin treatment such as HP20, low-temperature standing, filtration, etc. for decolorization and removal of unnecessary substances. Further, the extract can be used by fractionating a highly active fraction by an appropriate separation means such as a gel filtration method, a silica gel column chromatography method, or a reversed phase or normal phase high performance liquid chromatography method. In the present invention, the Sendangusa plant extract includes such a fraction. The obtained extract may be used as it is, or as a concentrate or a solid (eg, powder). Further, other components may be mixed according to the purpose of use.

(Antitussive or cough preventing composition)
The antitussive or cough preventing composition containing the Sendangusa genus plant extract of the present invention may be in any form, as an extract, or a liquid obtained by diluting or dissolving the extract with water or the like, or a powder, Oral administration as a solid such as a tablet may also be used. In the case of molding into tablets or the like, conventionally known carriers, powders, disintegrants, lubricants and the like can be used.
When using the composition of the present invention as an antitussive composition, it is preferable to administer about 0.001 to 10 g / kg (body weight) per day for adults in terms of Sendangusa plant extract (dry solid content).
When the composition of the present invention is used as a composition for preventing cough, it is preferable to administer about 0.001 to 10 g / kg (body weight) per day for an adult in terms of Sendangusa plant extract (dry solid content).
The composition of the present invention can also be used in the form of food. The form of the food may be a powder, a solid such as a tablet, or a drink such as a liquid. Examples of the type of food include confectionery such as cookies and strawberries, liquor items such as liquors, juices and soft drinks, seasonings such as miso and soy sauce, instant foods, so-called health supplements, and the like.

  Examples of cough-related diseases include cough asthma, sinus bronchial syndrome, chronic bronchitis, mycoplasma pneumonia, etc. "Continuous cough caused by diseases or causes with increased cough receptor sensitivity" such as converting enzyme inhibitors, postnasal drip, laryngeal allergy, persistent cough after cold syndrome, and non-asthmatic eosinophilic bronchitis .

(Induction of cough by capsaicin and cough suppression effect of Sendangsa spp.)
Capsaicin is known to stimulate C fibers, which are unmyelinated fibers of the sensory nervous system that cause cough, and it is known that inflammation-related mediators such as substance P are released by activation of capsaicin receptors. ing. In addition, the test that induces cough with capsaicin is a test that has been used for animals including humans for the purpose of cough sensitivity test or evaluation of treatment results for cough (Kamei, J., Tanihara, H Igarashi, H., Kasuya, Y .: Eur. J. Pharmacol., 168, 153-158 (1989); Dicpinigaitis, PV, Alva, RV: Chest, 128, 196-202 (2005)). From the above, it is considered that a substance capable of suppressing the cough reflex in humans or animals can be searched for by examining the inhibitory effect of the substance on the cough induction by capsaicin.
The cough induction test with capsaicin can be briefly described as follows: Capsaicin dissolved in a solvent such as dimethylsulfoxide is nebulized with a nebulizer, etc., and inhaled to an animal (guinea pig), and measured by measuring the number of coughing during capsaicin inhalation time. .

  After inducing cough with capsaicin as described above, a Cendungsa plant extract was administered, and cough was again induced with capsaicin after a certain period of time to confirm the cough-suppressing effect of the Cendungusa plant extract. The cough suppression rate was particularly high 60 minutes after administration of the plant extract of the genus Sendangusa. In addition, cough was suppressed depending on the dose of the plant of the genus Sendangsa (FIGS. 1 and 2).

(Induction of cough by capsaicin and suppression of cough by Sendangusa sp. Extract in ovalbumin-sensitized mice)
Ovalbumin is a glycoprotein with a molecular weight of 45,000, which is known as a substance that causes egg allergy. Ovalbumin was subcutaneously administered to mice twice a week apart to produce ovalbumin-sensitized mice (Iijima, H., Duguet, A., Eum, SY, Hamid, Q., Eidelman, DH: Am. J Respir. Crit. Care Med. 163, 1233-1240 (2001)), an allergic airway inflammation model was created by administering ovalbumin into the nasal cavity for 6 consecutive days. Since airway inflammation produces NO (nitrogen monoxide) and increases the amount released, NO concentration in the alveolar lavage fluid can be used as an indicator of airway inflammation (Iijima, H., Duguet, A., Eum, SY, Hamid, Q., Eidelman, DH: Am. J. Respir. Crit. Care Med. 163, 1233-1240 (2001)). In the airway inflammation model mouse, the amount of NO in the alveolar lavage fluid was significantly increased compared to the untreated mouse (FIG. 3).

When capsaicin was inhaled to the sensitized mice, the cough sensitivity increased and a marked increase in the number of cough reflexes was observed (FIG. 4—sensitized mice “front”). In such a model with increased cough sensitivity, even if dihydrocodeine, which has been conventionally used as an antitussive, is administered, only a weak antitussive effect is observed. On the other hand, when the Sendangusa plant extract is administered, the number of coughs is significantly reduced, and it can be seen that cough with enhanced cough sensitivity has a strong antitussive action (FIG. 4).
However, at this time, the amount of NO in the alveolar lavage fluid of the mice administered with the Sendangusa sp. Extract is almost the same as that of the control (the mice administered with the vehicle), and the Sendangsa sp. Extract against capsaicin-induced cough It is suggested that the inhibitory action of is not due to the NO-mediated anandamide transporter activation pathway.

(Induction of cough by anandamide and cough suppression by Sendangusa plant extract)
Anandamide is an endogenous ligand of the capsaicin receptor (Ross, RA: Br J Pharmacol., 140, 790-801, (2003)). Incorporation of anandamide activates the capsaicin receptor and enhances cough sensitivity. Since Candida extract significantly suppresses cough induction by anandamide (Fig. 6), Candida extract acts directly on anandamide transporter or capsaicin receptor to regulate C-fiber excitement and cough suppression It is thought that it shows an action.

Examples of the present invention will be described below.
<Examples of drug production>
100 kg of normal water is added to 10 kg of biden spiroza processed dried product (dried product processed by the method described in JP-A-2001-178390), and once boiled, it is extracted by keeping it at 95-100 ° C for 2 hours with occasional stirring. The extract, which was clarified by pressure filtration, was concentrated under reduced pressure, dissolved again in 5 L of water, heat-treated at 85 ° C for 30 minutes, dissolved uniformly with 600 g of dextrin, spray-dried, and 3.2 kg of extract A powder was obtained. Hereinafter, this is referred to as “biden spirosa extract”.

<Method for measuring the number of coughs>
The number of coughs was measured according to the plethysmograph method (Kamei, J., Tanihara, H., Igarashi, H., Kasuya, Y .: Eur. J. Pharmacol., 168, 153-158 (1989), Morita, K. , Kamei, J .: Eur. J. Pharmacol., 474, 269-272 (2003).). The plethysmograph used is made up of a cylinder part that houses the body of the experimental animal and a cap part that covers the head. An exhaust port was opened at the top of the cylinder so that it could be connected to a respiratory flow meter. In order to seal the inside of the cylinder, a collar made of rubber and celluloid was attached to the neck. The cap portion was opened with an inlet and a vent for capsaicin. The respiration was measured by measuring the movement of the thorax accompanying the respiration of the experimental animal in the cylinder through a respiratory flow meter as the volume change in the cylinder. When cough was induced, the thorax of the experimental animal moved vigorously, causing a large volume change temporarily in the cylinder, and this was measured by distinguishing it from normal breathing through a respiratory flow meter. This number was measured and used as the number of coughs.

<Drug administration method>
All drugs were suspended and dissolved in a 0.5% carboxymethylcellulose solution and orally administered (administered into the stomach with an oral sonde). The dose of bidenspirosa extract was 0.5, 1 and 2 g / kg based on the animal body weight.

<Statistical processing>
All data are shown as mean ± standard error of 6 guinea pigs or 10 mice. Changes in cough counts were compared using the Mann-Whitney U-test. A difference with a risk rate of 5% or less was determined to be significant. ANOVA (ANOVA) according to Bonferroni / Dunn test was used to compare the amount of NO in the alveolar lavage fluid, and those with a risk rate of 5% or less were judged to have a significant difference.

Example 1: Cough induction by capsaicin and cough suppression experiment by bidenspirosa extract <Induction of cough by capsaicin>
・ Induction of cough in mice (ICR male mice) (Morita, K., Kamei, J .: Eur. J. Pharmacol., 474, 269-272 (2003))
Cough was induced by inhalation of capsaicin (45 μM). Capsaicin was inhaled by making it into a mist with an ultrasonic nebulizer (Nihon Kohden: TUR-3200) and sending it with a ventilator (Shinano Seisakusho: SN-480-7). The average particle size of the fumed capsaicin was 4 μm, the ventilation of the ventilator was 10 ml, the rate was 30 times per minute, and the inhalation time was set to 3 minutes.
Induction of cough in guinea pigs (Hartley male guinea pigs) (Kamei, J., Tanihara, H., Igarashi, H., Kasuya, Y .: Eur. J. Pharmacol., 168, 153-158 (1989))
Elicited by inhalation of capsaicin (30 μM). Capsaicin was inhaled by making it into a mist with an ultrasonic nebulizer (Nihon Kohden: TUR-3200) and sending it with a ventilator (Shinano Seisakusho: SN-480-7). The average particle size of the fumed capsaicin was 4 μm, and the air supply by the ventilator was 20 ml of tidal volume at a rate of 30 times per minute, and the inhalation time was set to 7 minutes.
Capsaicin was dissolved in 10% ethanol and 10% Tween 80 solution and diluted with physiological saline before use.

<Bidenspirosa extract administration experiment>
Capsaicin was inhaled for 7 minutes (guinea pig) or 3 minutes (mouse) 30 minutes before administration of the bidenspirosa extract, and it was confirmed that cough was induced during this period, and the number of coughs was measured. Thereafter, bidenspirosa extract was administered, and capsaicin was inhaled again for 7 minutes (guinea pig) or 3 minutes (mouse) 60 minutes and 120 minutes after administration, and the number of cough induced during this period was measured.
The antitussive effect was evaluated by calculating the inhibition rate with respect to the number of cough before application of the drug from the number of cough before and after application of the drug using the following formula.
Cough suppression rate (%) = (number of cough before drug application-number of cough after drug application) / number of cough before drug application x 100

<Result>
The obtained results are shown in FIGS.
FIG. 1 is a graph showing the cough suppression rate (%) at each concentration 60 minutes and 120 minutes after administration of bidenspirosa extract in guinea pigs. At any concentration, the cough suppression rate was high 60 minutes after administration of the bidenspirosa extract, but the suppression effect almost disappeared after 120 minutes. When bidenspirosa extract was administered at a concentration of 2 g / kg, it was found that cough as high as 60% or more was suppressed.
FIG. 2 is a diagram showing cough suppression in guinea pigs at various concentrations 60 minutes after administration of bidenspirosa extract. In FIG. 2, “before” indicates the number of coughing induced by capsaicin, and “after” indicates the number of coughing when capsaicin is induced again 60 minutes after administration of the bidenspirosa extract. “Vehicle” means a 0.5% carboxymethyl cellulose solution without bidenspirosa extract (control). There was no change in the number of coughs in the control, but in the mice administered with bidenspirosa extract, the number of coughs decreased in a dose-dependent manner.

Example 2: Cough suppression experiment with bidenspirosa in ovalbumin-sensitized mice <Preparation of ovalbumin-sensitized mice and determination of NO amount in alveolar lavage fluid> (Iijima, H., Duguet, A., Eum, SY, Hamid, Q., Eidelman, DH: Am. J. Respir. Crit. Care Med. 163, 1233-1240 (2001).)
Four weeks old ICR male mice were used as sensitized animals. Ovalbumin 100 μg / 400 μl was dissolved in 4 mg / ml aluminum hydroxide and subcutaneously administered to two sites on the back and both heels. After 7 days, additional sensitization was performed in the same manner. Furthermore, from the 14th day, 10 μg / 50 μl of OVA was instilled under ether anesthesia for 6 days every day. The bidenspirosa extract was orally administered 24 hours after the last sensitization (day 19), and the alveolar lavage fluid was collected 1 hour after oral administration.

It recovered mouse lavage fluid (0.5 ml) centrifugation (15000 g × 10 min, 4 ° C.) and, NO metabolite contained in the supernatant _{^{(NO 2 - + NO 3 -}} ) for HPLC-Griess reaction system (Eicom It was measured by ENO-20).
The results are shown in FIG. After sensitization, NO in the alveolar lavage fluid of mice that had been instilled with OVA for 6 days (“OVA intraperitoneal administration + intranasal administration”) increased significantly compared to “untreated mice”, and inflammation of the respiratory tract Indicated. In addition, as a control, after sensitization, a mouse that had been nasalized with physiological saline instead of OVA was prepared, and the alveolar lavage fluid was collected and the NO amount measured in the same manner as in the untreated mouse. NO amount ("OVA intraperitoneally administered mouse").

<Induction of cough by capsaicin and suppression of cough by bidenspirosa in ovalbumin-sensitized mice>
Induced coughing with capsaicin in ovalbumin-sensitized and non-sensitized mice as in Example 1, administered 2 g / kg of bidenspirosa extract, and again induced coughing with capsaicin 60 minutes after administration. Measured (FIG. 4).
In addition, cough induction with capsaicin was performed on non-sensitized mice and sensitized mice in the same manner as in Example 1. Further, 2 g / kg of bidenspirosa extract or vehicle (control) was administered, and cough induction with capsaicin was again performed 60 minutes after administration. And the amount of each NO was measured (FIG. 5).

<Result>
In FIG. 4, “before” indicates the results of cough induction with capsaicin in ovalbumin-sensitized mice and non-sensitized mice, and “after” indicates coughing with capsaicin 60 minutes after administration of bidenspirosa extract 2 g / kg. The result of triggering is shown. In both sensitized and non-sensitized mice, administration of bidenspirosa extract significantly suppressed capsaicin-induced cough. In addition, when obalmin-sensitized mice were treated with capsaicin, a model with increased cough sensitivity and a very high number of coughs was obtained (“sensitized mice“ before ”). When bidenspirosa extract was administered to this sensitized mouse, cough was strongly suppressed. Dihydrocodeine, which is conventionally known as an antitussive, has a small cough-suppressing effect in a model in which ovalbumin-sensitized mice are cough-induced with capsaicin. Therefore, the effect of Bidenspirosa, which strongly suppresses cough in a model in which sensitization with obalmin and cough was induced with capsaicin, is a surprising effect.
From the results of FIG. 5, it is considered that the inhibitory action of bidenspirosa extract on capsaicin-induced cough is not due to the NO-mediated anandamide transporter activation pathway.

Example 3: Cough induction by anandamide and cough suppression experiment by bidenspirosa <Induction of cough by anandamide and cough suppression by bidenspirosa>
Anandamide 3 mg / ml (anandamide equivalent amount) in a 10% DMSO (dimethyl sulfoxide) solution was made into a mist with a nebulizer in the same manner as capsaicin in Example 1 and inhaled to mice to induce coughing. After inhalation of anandamide, 2 g / kg of bidenspirosa extract was orally administered, and 60 minutes after administration, cough induction with anandamide was performed again, and the number of coughs was measured.

  The results are shown in FIG. There was no change in the number of coughs in the control, but there was a decrease in the number of coughs in mice treated with bidenspirosa extract.

The antitussive action of bidenspirosa using guinea pigs is shown. Fig. 3 shows the dose dependence of antitussive action of bidenspirosa using guinea pigs. The increase in the amount of NO in the alveolar lavage fluid in mice sensitized with ovalbumin is shown. The effect of biden spirosa on the increase in the amount of NO in the alveolar lavage fluid in ovalbumin-sensitized mice is shown. 3 shows an increase in the number of capsaicin-induced coughs and the antitussive effect of bidenspirosa in ovalbumin-sensitized mice. 2 shows suppression of anandamide-induced cough by bidenspirosa.

Claims (5)

  An antitussive or cough preventing composition comprising an extract of a plant of the genus Sendungsa as an active ingredient.   The composition according to claim 1, which is for chronic cough.   The composition according to claim 1 or 2, wherein the extract of the genus Sendungusa is a hot water extract.   The composition according to any one of claims 1 to 3, wherein the plant of the genus Sendanga is biden spiroza.   It is a form of foodstuff, The composition as described in any one of Claims 1-4.

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