WO2016195526A1 - Sedative composition which reduces excitability during oestrus in cats and dogs - Google Patents

Sedative composition which reduces excitability during oestrus in cats and dogs Download PDF

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WO2016195526A1
WO2016195526A1 PCT/RU2015/000349 RU2015000349W WO2016195526A1 WO 2016195526 A1 WO2016195526 A1 WO 2016195526A1 RU 2015000349 W RU2015000349 W RU 2015000349W WO 2016195526 A1 WO2016195526 A1 WO 2016195526A1
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composition
theanine
dogs
cats
tryptophan
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PCT/RU2015/000349
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French (fr)
Russian (ru)
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Людмила Борисовна ТИМИРОВА
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Людмила Борисовна ТИМИРОВА
Денисов Дмитрий Евгеньевич
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Priority to PCT/RU2015/000349 priority Critical patent/WO2016195526A1/en
Publication of WO2016195526A1 publication Critical patent/WO2016195526A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia

Definitions

  • the invention relates to veterinary medicine and animal feeding, namely the production of sedatives for cats and dogs.
  • State of the art relates to veterinary medicine and animal feeding, namely the production of sedatives for cats and dogs.
  • Veterinary preparations, feed additives and other products for animals are known that have a calming and anti-stress effect that are used, including when excited by sexual hunting (Stop-stress, Cot-Bayun, etc.). They contain as active substances various groups of compounds (plant extracts, pheromone-like substances). However, these funds do not have a fast enough effect and during sexual arousal are used mainly as an additional tool.
  • the closest analogue of the invention are chewing tablets for dogs and cats "Anxitane®" (manufactured by Virbac Corporation, France), containing the active ingredient amino acid L-theanine. Tablets promote relaxation, relieve nervousness, anxiety, stress (L. Kern. La transmission de la dairy. In: La Communication. Collection Zoopsychiatrie, Beata C. ed. Marseille, Solal Editeurs, 2005).
  • L-Theanine an amino acid that is part of Anxitane®, has a calming and neuroprotective effect on laboratory animals (Vlasov TD, Barkovskaya A.A., Zukhurova M.A., Tsverina V.M. Mechanisms of the neuroprotective effect of green tea component - L-theanine / Regional blood circulation and microcirculation. - 2010.-N 4.- ⁇ .67-71.).
  • L-theanine as a sedative in the composition of feed additives, dietary supplements, in sports nutrition, as well as food products.
  • Anxitane® does not reduce arousal during sexual hunting in cats and dogs and has a long course of use to achieve a calming effect. Disclosure of invention
  • the objective of the invention was the creation on the basis of the amino acid L-theanine sedative for cats and dogs, which, unlike the analogue, has a quick action and effective, including during sexual hunting.
  • compositions based on the amino acid L-theanine and additional soothing components in particular glycine, tryptophan, ginger and valerian root, were studied.
  • Tests were carried out for each composition on 10 cats and 10 dogs of different ages, sex and different breeds in stressful situations (exhibitions, visits to a veterinarian, etc.), as well as those in arousal caused by sexual hunting. The results are presented in the examples below.
  • Excipients lactose, starch, dry whey, talc
  • flavor additives up to 0.3 g.
  • Tests have shown the calming effect of the composition only in cases where the arousal is not caused by the presence of sexual hunting or sexual arousal.
  • the composition did not have a calming effect in 4 cats that were in the period of sexual hunting and in 2 dogs in a state of sexual arousal.
  • This composition had a sedative effect in 36% of animals after application for 3 times a day. Almost had no effect on animals that are sexually aroused.
  • the composition had a long lasting soothing effect.
  • L-Tryptophan is an essential amino acid that, along with other amino acids, is widely used as a feed additive to balance the diets of farm and domestic animals.
  • a calming feed additive containing tryptophan (Equilizer (France)) is also known. horses with a pronounced reaction to stress and with increased nervousness.
  • tryptophan reduces sexual arousal during sexual hunting in animals.
  • the term “Theanine” (L-theanine, 1-thianine, 1-Theanine, 1-teanin) of the present invention is an amino acid derived from glutamic acid ( ⁇ -glutamyl ethylamide), obtained primarily from tea leaves, as well as synthetic and microbiological . Any form of the amino acid L-theanine, D-theanine and DL-theanine can be used, but it is preferable to use the L-form.
  • Theanine of the present invention can be used both as an amino acid and as an extract of green tea.
  • the tryptophan of the present invention can be 1-tryptophan, 5-hydroxytryptophan, plant extracts containing tryptophan and its derivatives and other biologically active forms of tryptophan and its derivatives obtained by various methods.
  • This composition had a calming effect on all animals, but the effect was less pronounced and not long.
  • the solution was used in a dose of 5 ml per 10 kg of body weight. Tests have shown that in the form of a solution, the composition is no less effective than the solid form and has a calming effect on all animals.
  • the optimal composition is the one containing theanine - 50 mg and tryptophan - 8 mg per 10 kg of animal body weight.
  • composition can be incorporated into feed additives, feed, treats and other feed products for cats and dogs. It can be used in combination with well-known auxiliary substances and excipients (lactose, starch, whey, cheese powder, milk flour, vegetable flour, meat flour, sugar syrup, broth and other feed and pharmaceutical ingredients).
  • the composition is effective both in the form of solid forms (for example, tablets), and in the composition of liquid feed products.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Fodder In General (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to veterinary science. A sedative composition with the effect of reducing sexual excitement in dogs and cats contains, in one dose per 10 kg body weight of the animal: 5-100 mg theanine; 2-16 mg tryptophan. The composition normalises the behaviour of an animal for a duration of 30-60 minutes after administration.

Description

УСПОКАИВАЮЩАЯ КОМПОЗИЦИЯ, ПОНИЖАЮЩАЯ ВОЗБУДИМОСТЬ ПРИ ПОЛОВОЙ ОХОТЕ У КОШЕК И СОБАК  CALMING COMPOSITION REDUCING EXCITABILITY IN SEXUAL HUNTING IN CATS AND DOGS
Описание изобретения Description of the invention
Область техники Technical field
Изобретение относится к ветеринарии и кормлению животных, а именно к производству успокаивающих средств для кошек и собак. Предшествующий уровень техники The invention relates to veterinary medicine and animal feeding, namely the production of sedatives for cats and dogs. State of the art
Известны ветеринарные препараты, кормовые добавки и другие продукты для животных обладающие успокаивающим и антистрессовым действием которые используют, в том числе и при возбуждении вызванном половой охотой (Стоп- стресс, Кот-баюн и др.). Они содержат в качестве действующих веществ различные группы соединений (экстракты растений, феромоноподобные вещества). Однако указанные средства обладают недостаточно быстрым действием и при половом возбуждении применяются в основном в качестве дополнительного средства. Veterinary preparations, feed additives and other products for animals are known that have a calming and anti-stress effect that are used, including when excited by sexual hunting (Stop-stress, Cot-Bayun, etc.). They contain as active substances various groups of compounds (plant extracts, pheromone-like substances). However, these funds do not have a fast enough effect and during sexual arousal are used mainly as an additional tool.
Известна также группа препаратов и добавок для животных, обладающих регулирующим половую охоту (и/или контрацептивным) действием (например Контрасекс, Стоп-секс и др.), содержащих гормональные и гормонально- подобные вещества. Однако они, в свою очередь не оказывают антистрессового, успокаивающего и улучшающего настроение животных действия. Кроме того, у данной группы средств имеются нежелательные побочные эффекты.  There is also a group of drugs and additives for animals with regulating sexual hunting (and / or contraceptive) action (for example, Contraex, Stop Sex, etc.) containing hormonal and hormone-like substances. However, they, in turn, do not have anti-stress, calming and mood-enhancing effects on animals. In addition, this group of drugs has undesirable side effects.
Наиболее близким аналогом изобретения являются жевательные таблетки для собак и кошек «Anxitane®» (производство корпорации Virbac, Франция), содержащие в качестве действующего вещества аминокислоту L-теанин. Таблетки способствуют релаксации, снимают нервозность, беспокойство, стресс (L. Kern. La transmission de la peur. In: La Communication. Collection Zoopsychiatrie, Beata C. ed. Marseille, Solal Editeurs, 2005). The closest analogue of the invention are chewing tablets for dogs and cats "Anxitane®" (manufactured by Virbac Corporation, France), containing the active ingredient amino acid L-theanine. Tablets promote relaxation, relieve nervousness, anxiety, stress (L. Kern. La transmission de la peur. In: La Communication. Collection Zoopsychiatrie, Beata C. ed. Marseille, Solal Editeurs, 2005).
L-Теанин - аминокислота входящая в состав «Anxitane®», оказывает успокаивающее и нейропротективное действие на лабораторных животных ( Власов Т.Д., Барковская А. А. , Зухурова М.А, Цверина В.М. Механизмы нейропротективного эффекта компонента зеленого чая - L-теанина/ Регионарное кровообращение и микроциркуляция.- 2010.-N 4.-С.67-71.).  L-Theanine, an amino acid that is part of Anxitane®, has a calming and neuroprotective effect on laboratory animals (Vlasov TD, Barkovskaya A.A., Zukhurova M.A., Tsverina V.M. Mechanisms of the neuroprotective effect of green tea component - L-theanine / Regional blood circulation and microcirculation. - 2010.-N 4.-С.67-71.).
Широко известно применение L-теанина в качестве успокаивающего средства в составе кормовых добавок, биологически активных добавок, в спортивном питании, а также пищевых продуктах.  It is widely known the use of L-theanine as a sedative in the composition of feed additives, dietary supplements, in sports nutrition, as well as food products.
Однако Anxitane® не снижает возбуждение при половой охоте у кошек и собак и имеет длительный курс применения для достижения успокаивающего эффекта. Раскрытие изобретения  However, Anxitane® does not reduce arousal during sexual hunting in cats and dogs and has a long course of use to achieve a calming effect. Disclosure of invention
Задачей изобретения являлось создание на основе аминокислоты L-теанина успокаивающего средства для кошек и собак, обладающего, в отличие от аналога, быстрым действием и эффективного, в том числе при половой охоте. The objective of the invention was the creation on the basis of the amino acid L-theanine sedative for cats and dogs, which, unlike the analogue, has a quick action and effective, including during sexual hunting.
Для достижения указанного технического результата изучались композиции на основе аминокислоты L-теанина и дополнительных успокаивающих компонентов в частности, глицина, триптофана, имбиря и корня валерианы.  To achieve the indicated technical result, compositions based on the amino acid L-theanine and additional soothing components, in particular glycine, tryptophan, ginger and valerian root, were studied.
Для испытаний были произведены опытные партии кормовых добавок в форме таблеток, содержащие разные композиции. Средства давались внутрь в дозировке 1 таблетка на 10 кг массы тела животного однократно между кормлениями.  For testing, pilot batches of feed additives in the form of tablets containing various compositions were produced. The funds were given orally at a dosage of 1 tablet per 10 kg of animal body weight once between feedings.
Испытания проводились по каждой композиции на 10 кошках и 10 собаках разного возраста, пола и разных пород, находящихся в стрессовых ситуациях (выставки, посещение ветеринарного врача и др.), а также находящихся в возбуждении вызванном половой охотой. Результаты представлены в нижеприведенных примерах. Tests were carried out for each composition on 10 cats and 10 dogs of different ages, sex and different breeds in stressful situations (exhibitions, visits to a veterinarian, etc.), as well as those in arousal caused by sexual hunting. The results are presented in the examples below.
Пример 1. Example 1
Композиция ° 1 Composition ° 1
Теанин - 50 мг Theanine - 50 mg
Глицин - 10 мг Glycine - 10 mg
Вспомогательные вещества (лактоза, крахмал, сыворотка подсырная сухая, тальк) и вкусоароматические добавки - до 0,3 г.  Excipients (lactose, starch, dry whey, talc) and flavor additives - up to 0.3 g.
Испытания показали наличие успокаивающего эффекта композиции только в случаях, когда возбуждение не вызвано наличием половой охоты или полового возбуждения. Композиция не оказала успокаивающего действия у 4 кошек, находившихся в периоде половой охоты и у 2 кобелей, находящихся в состоянии полового возбуждения.  Tests have shown the calming effect of the composition only in cases where the arousal is not caused by the presence of sexual hunting or sexual arousal. The composition did not have a calming effect in 4 cats that were in the period of sexual hunting and in 2 dogs in a state of sexual arousal.
Пример 2.  Example 2
Композиция Ν° 2  Composition Ν ° 2
Теанин - 50 мг Theanine - 50 mg
Имбирь - 45 мг,  Ginger - 45 mg
Корень валерианы - 45 мг  Valerian Root - 45 mg
Вспомогательные вещества и вкусоароматические добавки - до 0,3 г.  Excipients and flavoring additives - up to 0.3 g.
Данная композиция оказывала успокоительный эффект у 36% животных после применения в течение 3-х раз в день. Практически не оказала действия на животных, находящихся в половом возбуждении.  This composition had a sedative effect in 36% of animals after application for 3 times a day. Almost had no effect on animals that are sexually aroused.
Пример 3.  Example 3
Композиция Ν° 3  Composition Ν ° 3
Теанин - 50 мг  Theanine - 50 mg
Триптофан - 8 мг Tryptophan - 8 mg
Вспомогательные вещества и вкусоароматические добавки - до 0,3 г.  Excipients and flavoring additives - up to 0.3 g.
Композиция оказала длительное хорошее успокаивающее действие. The composition had a long lasting soothing effect.
Поведение животных нормализовалось в течение от 30 мин до 1 часа после поедания таблеток у всех животных и оставалось в норме в течение суток наблюдения. The behavior of animals returned to normal within 30 minutes to 1 hour after eating tablets in all animals and remained normal during the day of observation.
Таким образом, только сочетание двух аминокислот теанина и триптофана, оказывает достаточно быстрый успокаивающий эффект (от 30 до 60 минут) и проявляет новое дополнительное действие - а именно, выраженное подавление возбуждения вызванного половой охотой.  Thus, only a combination of the two amino acids theanine and tryptophan has a fairly quick calming effect (from 30 to 60 minutes) and exhibits a new additional effect - namely, a pronounced suppression of excitation caused by sexual hunting.
L-Триптофан - незаменимая аминокислота, которая наряду с другими аминокислотами широко применяется в качестве кормовой добавки для балансирования рационов сельскохозяйственных и домашних животных. Известна также успокаивающая кормовая добавка, содержащая триптофан (Эквилайзер (Франция)) для . лошадей с выраженной реакцией на стресс и с повышенной нервозностью.  L-Tryptophan is an essential amino acid that, along with other amino acids, is widely used as a feed additive to balance the diets of farm and domestic animals. A calming feed additive containing tryptophan (Equilizer (France)) is also known. horses with a pronounced reaction to stress and with increased nervousness.
Установлено, что пептиды, содержащие триптофан (8 г/ 100 г) в дозе 0,01- 0,02 г/кг массы тела вызывают снотворное действие у лабораторных животных в течение 30-40 минут (RU 2043364, 10.09.1995).  It was found that peptides containing tryptophan (8 g / 100 g) at a dose of 0.01-0.02 g / kg body weight cause sleeping pills in laboratory animals for 30-40 minutes (RU 2043364, 09/10/1995).
Однако не установлено, что триптофан снижает половое возбуждение в период половой охоты у животных.  However, it has not been established that tryptophan reduces sexual arousal during sexual hunting in animals.
Термин «Теанин» (L-теанин, 1-тианин, 1-Theanine, 1-teanin) по настоящему изобретению представляет собой аминокислоту, производное глутаминовой кислоты (γ-глутамил этиламид), получаемую преимущественно из листьев чая, а также синтетическим и микробиологическим путем. Возможно применение любой формы аминокислоты - L-теанина, D-теанина и DL-теанина, но предпочтительно использование L-формы. Теанин по настоящему изобретению может применяться как в виде аминокислоты, так и в виде экстракта зеленого чая.  The term “Theanine” (L-theanine, 1-thianine, 1-Theanine, 1-teanin) of the present invention is an amino acid derived from glutamic acid (γ-glutamyl ethylamide), obtained primarily from tea leaves, as well as synthetic and microbiological . Any form of the amino acid L-theanine, D-theanine and DL-theanine can be used, but it is preferable to use the L-form. Theanine of the present invention can be used both as an amino acid and as an extract of green tea.
Триптофан по настоящему изобретению может представлять собой 1- триптофан, 5-гидрокситриптофан, экстракты растений содержащие триптофан и его производные и другие биологически активные формы триптофана и его производных, полученные различными методами. Варианты осуществления изобретения The tryptophan of the present invention can be 1-tryptophan, 5-hydroxytryptophan, plant extracts containing tryptophan and its derivatives and other biologically active forms of tryptophan and its derivatives obtained by various methods. Embodiments of the invention
Для определения наиболее эффективной концентрации аминокислот изучались различные дозировки теанина и триптофана и способы введения, что иллюстрируется следующими примерами, To determine the most effective concentration of amino acids, various dosages of theanine and tryptophan and methods of administration were studied, which is illustrated by the following examples,
Пример 4. Example 4
Композиция Ν» 4  Composition Ν »4
Теанин - 5 мг Theanine - 5 mg
Триптофан - 2 мг Tryptophan - 2 mg
Вспомогательные вещества и вкусоароматические добавки - до 0,3 г.  Excipients and flavoring additives - up to 0.3 g.
Данная композиция оказывала успокаивающее действие на всех животных, однако действие было менее выраженным и не длительным.  This composition had a calming effect on all animals, but the effect was less pronounced and not long.
Пример 5.  Example 5
Композиция JNb5  Composition JNb5
Теанин - 100 мг  Theanine - 100 mg
Триптофан - 16 мг Tryptophan - 16 mg
Вспомогательные вещества и вкусоароматические добавки - до 0,3 г.  Excipients and flavoring additives - up to 0.3 g.
Применение этой композиции также успокаивало всех животных, но имело побочное действие, в частности, часть животных были в сонном состоянии. The use of this composition also calmed all animals, but had a side effect, in particular, some of the animals were in a sleepy state.
Пример 6. Example 6
Композиция N°6 Composition N ° 6
Теанин - 50 мг  Theanine - 50 mg
Триптофан - 8 мг  Tryptophan - 8 mg
Вода дистиллированная, стабилизатор, консервант, вкусоароматическая добавка - до 5 мл.  Distilled water, stabilizer, preservative, flavoring additive - up to 5 ml.
Раствор применялся в дозе 5 мл на 10 кг массы тела. Испытания показали, что в форме раствора композиция не менее эффективна, чем твердая форма и оказывает успокаивающее действие на всех животных.  The solution was used in a dose of 5 ml per 10 kg of body weight. Tests have shown that in the form of a solution, the composition is no less effective than the solid form and has a calming effect on all animals.
Как следует из примеров, все испытанные дозировки теанина и триптофана достаточны для достижения заявленного технического результата, но наиболее б As follows from the examples, all the tested dosages of theanine and tryptophan are sufficient to achieve the claimed technical result, but the most b
оптимальной является композиция, содержащая теанин - 50 мг и триптофан - 8 мг на 10 кг массы тела животного. the optimal composition is the one containing theanine - 50 mg and tryptophan - 8 mg per 10 kg of animal body weight.
Промышленная применимость Композиция может быть введена в состав кормовых добавок, корма, лакомства и другие кормовые продукты для кошек и собак. Может применяться в сочетании с известными вспомогательными веществами и наполнителями (лактоза, крахмал, сыворотка подсырная, молоко сухое, мука растительная, мука мясная, сахарный сироп, бульон и другие кормовые и фармацевтические ингредиенты). INDUSTRIAL APPLICABILITY The composition can be incorporated into feed additives, feed, treats and other feed products for cats and dogs. It can be used in combination with well-known auxiliary substances and excipients (lactose, starch, whey, cheese powder, milk flour, vegetable flour, meat flour, sugar syrup, broth and other feed and pharmaceutical ingredients).
Композиция эффективна как в форме твердых форм (например, таблеток), так и в составе жидких кормовых продуктов.  The composition is effective both in the form of solid forms (for example, tablets), and in the composition of liquid feed products.

Claims

Формула изобретения Claim
Успокаивающая композиция с понижающим половое возбуждение Действием для собак и кошек, содержащая в одной дозе на 10 кг массы тела животного: теанин - от 5 до 100 мг Calming composition with reducing sexual arousal Action for dogs and cats, containing in a single dose per 10 kg of animal body weight: theanine - from 5 to 100 mg
триптофан - от 2 до 16 мг. tryptophan - from 2 to 16 mg.
ЗАМЕНЯЮЩИЙ ЛИСТ (ПРАВИЛО 26) SUBSTITUTE SHEET (RULE 26)
PCT/RU2015/000349 2015-06-03 2015-06-03 Sedative composition which reduces excitability during oestrus in cats and dogs WO2016195526A1 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080044499A1 (en) * 2004-04-06 2008-02-21 Taiyokagaku Co., Ltd. Sleep Improvement Composition
RU2479316C2 (en) * 2007-09-04 2013-04-20 Дзе Проктер Энд Гэмбл Компани Oral compositions, products and methods of use

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080044499A1 (en) * 2004-04-06 2008-02-21 Taiyokagaku Co., Ltd. Sleep Improvement Composition
RU2479316C2 (en) * 2007-09-04 2013-04-20 Дзе Проктер Энд Гэмбл Компани Oral compositions, products and methods of use

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