WO2021203146A1 - Pain-relieving and anti-inflammatory preparation for preventing and treating thrombosis - Google Patents
Pain-relieving and anti-inflammatory preparation for preventing and treating thrombosis Download PDFInfo
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- WO2021203146A1 WO2021203146A1 PCT/VN2021/000006 VN2021000006W WO2021203146A1 WO 2021203146 A1 WO2021203146 A1 WO 2021203146A1 VN 2021000006 W VN2021000006 W VN 2021000006W WO 2021203146 A1 WO2021203146 A1 WO 2021203146A1
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- pain
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Definitions
- the present invention relates to the field of traditional medicines, in particular to a pain-relieving anti-inflammatory preparation for preventing and treating thrombosis using natural medicinal herds.
- Coagulation is a naturally occurring process that allows blood cells to clump together and form a blood clot or blood clot. This process is beneficial, especially when the body is damaged causing bleeding. And although most natural clots can dissolve on their own without complications, there are situations where they can be life-threatening, such as those that form in arteries, which can clog the arteiy and cut off oxygen supply to part of the body. Consequently, it can cause heart attacks, damage and/or destroy blood vessel walls (infarction), cause death of heart tissue in the patients. In the brain, a blood clot also blocks blood and oxygen from reaching the area it needs, which can lead to senility and/or stroke.
- the present invention particularly relates to a pain-relieving and anti-inflammatory preparation for preventing and treating thrombosis, wherein the preparation comprises components as follows: the blood activating component; the qi-blood tonifying and drug delivering component; the bone tonifying and pain-relieving component; and excipients.
- the blood activating component comprises at least three of the medicinal herbs comprising: Nattokinase, Dangshen ( Radix Salviae militiorrhizae), Szechuan lovage ( Rhizoma Ligustici wa wallichii), Safflower (Carthamus tinctorius), Fo-Ti (Fallopia multiflora), Dongquai ( Radix Angelicae sinensis ), E Jiao ( Colta Asini), Chinese peony (. Radix Paeoniae lactiflorae ), Medicinal leech ( Hirudo medicinalis), Earthworm ( Pheretima aspergilum) or medicinal herbs with equivalent effects.
- the blood activating component comprises at least four of these medicinal herbs. Most preferably, the blood activating component comprises at least five of these medicinal herbs.
- the blood activating component comprises: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech.
- the blood activating component comprises: Nattokinase, Szechuan lovage, Dongquai, Chinese peony and Medicinal leech.
- the qi-blood tonifying and drug delivering component comprises at least one of the medicinal herbs comprising: Ginseng ( Panax gingseng), Bai Zhu (Atractylodes macrocephala) , Dangshen ( Radix Codonnopsis ), Jujube fruit (Fructus Ziziphi Jujubae) ( Fructus Ziziphi jujubae ), Notoginseng (.
- the blood activating component comprises at least two or three of these medicinal herbs. Most preferably, the blood activating component comprises at least four or five of these medicinal herbs.
- the qi-blood tonifying and drug delivering component comprises: Dangshen, Notoginseng, Liquorice, Peach blossom and Cinnamon.
- Dangshen and Cinnamon’s properties are light, flexible and effective in leading medicine upwards in the body.
- Dangshen and Cinnamon instead of Ginseng and Cortex Cinnamomi that have been used in the existing remedies, combined with White willow, Peach blossom and Notoginseng makes the preparation of the present invention gain unexpected effects, compared with existing remedies including neck traditional remedies, in effectively delivering the active components to the upper body parts such as head, shoulder, back neck, neck, leading in more effective treatment of secondary or primary inflammatory pains.
- the bone tonifying and pain-relieving component comprises at least seven in the medicinal herbs comprising: Hardy rubber tree ( Cortex Eucommiae), Qian Nian Jian (Rhizoma Homalomenae) , Chinese Tinospora (Tinospora sinensis ), Tu Fu-ling (Smilax glabra), Du Huo ( Radix Angelicae pubescentis ), Qiang Huo (Notopterygium incisium), Ox Knee ( Radix Achyranthis bidentatae ), Large cocklebur (Xanthium strumarium ), Ivy Tree (Schefflera heptaphylla), Strychnine tree (Strychnos nux - vomica), Fang Feng ( Radix Saposhnikoviae divaricatae ), Sang Ji Sheng ( Herba Taxilli ), Gentian Root ⁇ Radix Gentianae), St Paul’s-wort (Sigesbeckia orientalis), Cang Zhu (
- the bone tonifying and pain- relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove and White willow.
- the bone tonifying and pain-relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove.
- the bone tonifying and pain-relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Fu-ling, Chinese foxglove, Xi Xin and White willow.
- the preparation of the present invention further comprises neurotransmitters.
- Said neurotransmitters comprises at least one in the medicinal herbs comprising: Velvet bean (Semen Mucuna pruriens) and Stag’s-hom clubmoss (Lycopodium clavatum L .) or medicinal herbs with equivalent effects.
- said neurotransmitters comprises Velvet bean and Stag’s-hom clubmoss.
- the preparation of the present invention comprises components in percentage by weight as follows: the blood activating component: 20-50%, preferably 25-45%, most preferably 30-40%, in a particular embodiment the blood activating component is of 30%; the qi-blood tonifying and drug delivering component: 2-40%, preferably 5- 30%, most preferably 10-20%, in a particular embodiment the qi-blood tonifying and drug delivering component is of 10%; the bone tonifying and pain-relieving component: 5-40 preferably 10-30%, most preferably 15-20%, in a particular embodiment the bone tonifying and pain- relieving component is of 30%; neurotransmitters: 0-35%, preferably 5-30%, most preferably 10-25%; in a particular embodiment neurotransmitters is of 25%; and excipients, q.s. to 100%.
- the blood activating component comprises in percentage by weight:
- Nattokinase 25-95%, preferably 30-90%, most preferably 35-85%;
- Medicinal leech, Earthworm* 0-25%, preferably 2-22%, most preferably 5-
- Fo-Ti, Dongquai, E Jiao* 2-30%, preferably 7-27%, most preferably 10- 25%;
- Chinese peony 0-30%, preferably 7-27%, most preferably 10-25%.
- the qi-blood tonifying and drug delivering component comprises in percentage by weight:
- Ginseng, Bai Zhu, Dangshen* 20-60%, preferably 25-55%, most preferably 30-50%;
- Jujube fruit, Notoginseng, Mongolian milkvetch* 0-35%, preferably 5-30%, most preferably 7-27%;
- Liquorice 0-20%, preferably 5-17%, most preferably 7-15%;
- Peach blossom 0-35%, preferably 5-30%, most preferably 7-27%;
- Cinnamon 0-45%, preferably 5-42%, most preferably 7-40%.
- the bone tonifying and pain- relieving component comprises comprises in percentage by weight:
- Sang Ji Sheng 0.5-20%, preferably 1-17%, most preferably 2-12%;
- the neurotransmitters comprises in percentage by weight:
- Extract of Stag’s-hom clubmoss 0-70%, preferably 20-65%, most preferably 25-60%;
- Velvet bean 0-70%, preferably 20-65%, most preferably 25-60%.
- the preparation of the present invention further comprises excipients of natri benzoat, magie stearat and talc powder q.s. to 100% of the preparation weight.
- FIG.l is the micro-histological image of the control group in the pharmacological study cua Example 1, which showed a wide centeral degenerative region with multiple degenerative polymorphonuclear leukocytes.
- FIG.2 is the micro-histological image of the control group in the anti inflammatory study, which showed that the degenerative wall had many fibroblasts and polymorphonuclear leukocytes and lymphocytes.
- FIG.3 is the micro-histological image of the orally methylprednisolon group with concentration of 10 mg/kg, which showed the much appearance of polymorphonuclear leukocytes in the internal area.
- FIG.4 is the micro-histological image of the orally methylprednisolon group with concentration of 10 mg/kg, which showed the less appearance of polymorphonuclear leukocytes in the external area.
- FIG.5 is the anatomic image of rat tissue after oral administration of the preparation of a low dose of 0.54 capsule/kg/day. The image showed that the necrotic areas contained many polymorphonuclear leukocytes, but do not contain any lymphocytes after 10-day oral administration of CT1.
- FIG.6 is the anatomic image of rat tissue afer oral administration of the preparation of a low dose of 0.54 capsule/kg/day. The image showed that the peripheral areas contain additionally many polymorphonuclear leukocytes and lymphocytes after 10-day oral administration of CT1.
- FIG.7 is the anatomic image of rat tissue after oral administration of the preparation with a high dose of 1.62 capsule/kg/day. The image showed that the necrotic areas contain many polymorphonuclear leukocytes and contain few lymphocyte after 10-day oral administration of CT1.
- FIG.8 is the anatomic image of rat tissue after oral administration of the preparation with a high dose of 1.62 capsule/kg/day. The image showed that that the peripheral areas appear additionally many polymorphonuclear leukocytes and lymphocytes after 10-day oral administration of CT1.
- weights are represented in percentage by weight, when referring to a percentage range of a particular component, for example ‘in a/the range of A to B%’ means to include both A and B values and any values between A and B.
- percentage value for example ‘C%’ is defined as a range around the C value, which is usually 10% greater or less. This ensures that the variants of the present invention are realized clearly and within the tolerances for mixing multiple components together.
- the blood activating component of the present invention enhances blood circulation, reduces the formation of thrombosis, this component is in the range of 20-50%, preferably 25-45%, most preferably 30-40% by weight of the preparation.
- the amount of the blood activating component in the preparation of the present invention is 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50% by weight of the preparation.
- the blood activating component comprises at least three, preferably four, and most preferably five of the medicinal herbs in percentage by weight as follows: Nattokinase, Medicinal leech, Earthworm, Dangshen, Szechuan lovage, Safflower, Fo-Ti, Dongquai, E Jiao and Chinese peony.
- an amount of Nattokinase in the blood activating component is in a range of 25-95%, preferably 30-90% and most preferably of 35-85% by weight of the blood activating component. In some particular embodiments, an amount of Nattokinase in the blood activating component is 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or 95% by weight of the blood activating component. In the most preferable embodiment, Nattokinase used most preferably is 60% by weight of the blood activating component.
- an amount of Medicinal leech and/or Earthworm in the blood activating component is in a range of 0-25%, preferably 2- 22% and most preferably 5-20% by weight of the blood activating component.
- an amount of Medicinal leech and or Earthworm in the blood activating component is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25% by weight of the blood activating component.
- an amount of Medicinal leech used is most preferably 20% by weight of the blood activating component.
- an amount of Dangshen, Szechuan lovage, Safflower, or a combination of at least two of them in the blood activating component is in a range of 0.1-10%, preferably 0.2-8% and most preferably 0.5- 6% by weight of the blood activating component.
- an amount of Dangshen, Szechuan lovage, Safflower, or a combination of at least two of them in the blood activating component is 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10% by weight of the blood activating component.
- an amount of Dongquai used is most preferably 2% by weight of the blood activating component.
- an amount of Fo-Ti, Dongquai, E Jiao, or a combination of at least two of them in the blood activating component is in a range of 2-30%, preferably 7-27% and most preferably 10-25% by weight of the blood activating component.
- an amount of Fo-Ti, Dongquai, E Jiao, or a combination of at least two of them in the blood activating component is 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or 30% by weight of the blood activating component.
- an amount of Dongquai used is most preferably 20% by weight of the blood activating component.
- an amount of Chinese peony in the blood activating component is in a range of 0-30%, preferably 7-27% and most preferably 10-25% by weight of the blood activating component.
- an amount of Chinese peony in the blood activating component is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30% by weight of the blood activating component.
- an amount of Chinese peony used is most preferably 20% by weight of the blood activating component.
- the qi-blood tonifying and drug delivering component of the present invention enhances and tonifies qi-blood, leading the drugs, therefore this component increases therapeutic effect while enhancing the health of patients.
- the qi-blood tonifying and drug delivering component is in the range of 2-40%, preferably 5-30% and most preferably 10-20% by weight of the preparation.
- an amount of the qi-blood tonifying and drug delivering component in the preparation of the present invention is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40% by weight of the preparation.
- the qi-blood tonifying and drug delivering component of the present invention comprises at least one, preferably two or three and most preferably four of the following medicinal herbs: Ginseng, Bai Zhu, Dangshen, Jujube fruit, Notoginseng, Mongolian milkvetch, Liquorice, Peach blossom and Cinnamon.
- an amount of Ginseng, Bai Zhu, Dangshen or a combination of at least two of them used is in a range of 20-60%, preferably 25-55% and most preferably 30-50% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Ginseng, Bai Zhu, Dangshen or a combination of at least two of them in the qi-blood tonifying and drug delivering component is 20, 25, 30, 35, 40, 45, 50, 55 or 60% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Dangshen used is most preferably 30% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Jujube fruit, Notoginseng, Mongolian milkvetch or a combination of at least two of them used is in a range of 0-35%, preferably 5-30% and most preferably 7-27% by weight of the qi-blood tonifying and drug delivering component.
- Jujube fruit, Notoginseng, Mongolian milkvetch or a combination of at least two of them in the qi-blood tonifying and drug delivering component is 0, 5, 10, 15, 20, 25, 30 or 35% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Notoginseng used is most preferably 25% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Liquorice used is in a range of 0-20%, preferably 5-17% and most preferably 7-15% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Liquorice in the qi-blood tonifying and drug delivering component is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Liquorice used is most preferably 15% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Peach blossom used is in a range of 0-35%, preferably 5-30% and most preferably 7-27% by weight of the qi- blood tonifying and drug delivering component.
- an amount of Peach blossom in the qi-blood tonifying and drug delivering component is 0, 0.5, 1, 5, 10, 15, 20, 25, 30 or 35% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Peach blossom used is most preferably 20% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Cinnamon used is in a range of 0-45%, preferably 5-42% and most preferably 7-40% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Cinnamon in the qi-blood tonifying and drug delivering component is 0, 5, 10, 15, 20, 25, 30, 35, 40 or 55% by weight of the qi-blood tonifying and drug delivering component.
- an amount of Cinnamon used is most preferably 30% by weight of the qi-blood tonifying and drug delivering component.
- the bone tonifying and pain-relieving component in combination with the blood activating component increases the effect of treating thrombosis.
- thrombosis relating diseases often cause inflammation and bleeding in the internal vessel walls of thrombosis leading in pains.
- the bone tonifying and pain-relieving component in the preparation is in the range of 5-40% by weight of the preparation.
- the bone tonifying and pain-relieving component in the preparation of the present invention preferably is in a range of 10-30% by weight of the preparation, more preferably is is in a range of 15-20% by weight of the preparation.
- the amount of the bone tonifying and pain-relieving component in the preparation of the present invention is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40% by weight of the preparation.
- the bone tonifying and pain-relieving component comprises at least seven, preferably eight or nine, most preferably ten of the following medicinal herbs: Extract of White willow, other species belonging to Salix, Hardy rubber tree, Qian Nian Jian, Chinese Tinospora, Tu Fu-ling, Du Huo, Qiang Huo, Ox Knee, Large cocklebur, Ivy Tree, Strychnine tree, Fang Feng, Sang Ji Sheng, Gentian Root, St Paul’s-wort, Cang Zhu, Tu Fu-ling, Fu-ling, Chinese foxglove, Chinese Foxglove, Ginger, Xi Xin and Bai Zhi.
- an amount of White willow and/or other species belonging to Salix used is in a range of 0-80%, preferably 25-65% and most preferably 30-60% by weight of the bone tonifying and pain-relieving component.
- an amount of White willow in the bone tonifying and pain-relieving component is 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 or 80% by weight of the bone tonifying and pain-relieving component.
- an amount of White willow used is most preferably 50% by weight of the bone tonifying and pain-relieving component.
- an amount of Hardy rubber tree and/or Qian Nian Jian used is in a range of 1-20%, preferably 5-17% and most preferably 7- 15% by weight of the bone tonifying and pain-relieving component.
- an amount of Hardy rubber tree in the bone tonifying and pain-relieving component is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% by weight of the bone tonifying and pain-relieving component.
- an amount of Hardy rubber tree used is most preferably 12% by weight of the bone tonifying and pain-relieving component.
- an amount of Chinese Tinospora, Tu Fu- ling, Du Huo, Qiang Huo or a combination of at least two of them used is in a range of 0.5-20%, preferably 1-17% and most preferably 2-12% by weight of the bone tonifying and pain-relieving component.
- an amount of Du Huo in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain- relieving component.
- an amount of Du Huo used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
- an amount of Ox Knee, Large cocklebur, Ivy Tree or a combination of at least two of them used is in a range of 0.5-20%, preferably 1-17% and most preferably 2-12% by weight of the bone tonifying and pain-relieving component.
- an amount of Ox Knee in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component.
- an amount of Ox Knee used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
- an amount of Fang Feng and/or Strychnine tree used is in a range of 0.5-20%, preferably 1-17% and most preferably 2-12% by weight of the bone tonifying and pain-relieving component.
- an amount of Fang Feng in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component.
- an amount of Fang Feng used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
- an amount of Sang Ji Sheng is used in a range of 0.5-20%, preferably 1-17% by weight of the bone tonifying and pain- relieving component.
- an amount of Sang Ji Sheng in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component.
- an amount of Sang Ji Sheng used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
- an amount of Gentian Root, St PauTs-wort, Cang Zhu or a combination of at least two of them used is in a range of 0.5-20%, preferably 1-17% by weight of the bone tonifying and pain-relieving component.
- an amount of Gentian Root in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component.
- an amount of Gentian Root used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
- an amount of Fu-ling and/or Tu Fu-ling used is in a range of 0-18%, preferably 5-17% and most preferably 7-15% by weight of the bone tonifying and pain-relieving component.
- an amount of Fu-ling in the bone tonifying and pain-relieving component is 0, 3, 5, 7, 9, 11, 13, 15, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component.
- an amount of Fu-ling used is most preferably 12% by weight of the bone tonifying and pain-relieving component.
- an amount of Chinese foxglove and/or Chinese Foxglove used is in a range of 5-20%, preferably 5-17% and most preferably 7-15% by weight of the bone tonifying and pain-relieving component.
- an amount of Chinese foxglove in the bone tonifying and pain-relieving component is 5, 10, 15, 17 or 20% by weight of the bone tonifying and pain-relieving component.
- an amount of Chinese foxglove used is most preferably 12% by weight of the bone tonifying and pain-relieving component.
- an amount of Ginger, Xi Xin, Bai Zhi or a combination of at least two of them used is in a range of 0-15%, preferably 0.2- 12% and most preferably 0.5-10% by weight of the bone tonifying and pain- relieving component.
- an amount of Xi Xin in the bone tonifying and pain-relieving component is 0.1, 0.2, 0.5, 0.7, 1, 1.2, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10% by weight of the bone tonifying and pain-relieving component.
- an amount of Xi Xin used is most preferably 6% by weight of the bone tonifying and pain-relieving component.
- Neurotransmitters in the preparation of the present invention is for sedation, reducing symtoms of memory loss due to the embolism impact by thrombosis, helping to restore the nervous system damages.
- the neurotransmitters in the preparation of the present invention comprises Velvet bean and Stag’s-hom clubmoss, in the range of 0-35%, preferably 5-30%, most preferably 10-25% by weight of the preparation.
- an amount of Velvet bean used is in a range of 0-70%, preferably 20-65%, and most preferably 25-60% by weight of the neurotransmitters. In some particular embodiments, an amount of Velvet bean in the neurotransmitters is 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or 70% by weight of the neurotransmitters. In the most preferable embodiment, an amount of Velvet bean used is most preferably 40% by weight of the neurotransmitters.
- an amount of Stag’s-hom clubmoss used is in a range of 0-70%, preferably 20-65%, and most preferably 25-60% by weight of the neurotransmitters.
- an amount of Velvet bean in the neurotransmitters is 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or 70% by weight of the neurotransmitters.
- an amount of Velvet bean used is most preferably 60% by weight of the neurotransmitters.
- the preparation of the present invention further comprises excipients including natri benzoat, talc, magie stearat.
- excipients include natri benzoat, talc, magie stearat.
- These excipients play the roles of fillers, preservatives or flavor enhancers.
- These excipients can be substituted by other ones, depending on the purposes of use in the preparation, thus known by a person in the field. Such excipients are known and available for sale.
- the preparation of the present invention consists of a bone tonifying and pain-relieving component including at least Hardy mbber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove and White willow.
- the preparation of the present invention consists of components the blood activating component including at least: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech; and the bone tonifying and pain-relieving component including at least: Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove; and neurotransmitters including: Velvet bean and Stag’s-hom clubmoss.
- the blood activating component including at least: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech
- the bone tonifying and pain-relieving component including at least: Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove
- neurotransmitters including: Velvet bean and Stag’s-hom clubmoss.
- the preparation of the present invention consists of the bone tonifying and pain-relieving component including at least: Hardy mbber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove and White willow; the blood activating component including at least: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech; the bone tonifying and pain-relieving component including at least: Hardy mbber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove; and the neurotransmitters including: Velvet bean and Stag’s-hom clubmoss.
- the preparation of the present invention is useful for pain-relieving and anti inflammatory and for preventing and treating thrombosis.
- the preparation therefore, are effective in treating musculoskeletal and joints diseases, pains of neck, shoulder, back neck due to cervical degenerative disease, herniated disc leading in compression of nerves and blood vessels, obstructing cerebral circulation.
- the preparation is also useful for treatmenting and/or protecting cerebral vessels because of vasodilation, protecting blood vessel walls, supporting treatment of complications caused by strokes.
- each component can be prepared individually, then mixed at defined proportions; or all components can be prepared at the same time at defined proportions; or in any known proper techniques.
- - Medicinal leech is prepared by selecting large and strong leeches, then soaking them with alcohol to their death. The dead leaches are picked out, washed, then cut open, turned the entire intestine out. Then they are rinsed with saline water for several times, following by boiled up, cu tinto pieces and then dried. After that, the dried Medicinal leeches are grinded into powder. Then said powder is sifted using 0.2mm sieve to obtain Medicinal leach powders.
- the obtained concentrate can be added with nipagin and nipasol that have been dissolved in an enough amout of 96% ethanol, while stirring. Then the obtained material is poured into moulds to obtain concentrated extract cakes having moisture content of 20%. These cakes are cut into thin slices of about 3-5cm thickness. The thin slices are preaded over a tray and put in a static oven, dried at a temperature of about 85 °C to dry. The dried product is let to cool in the room temperature then finely grinded with a hammer mill, then sifted through a 0.2mm sieve to obtain powders, each has a moisture content of about 5%.
- - Nattokinase extract is prepared by soaking soybeean seeds, peeling off the skin, riped up, adding Baccillus natto, then incubating at 42°C for 5 hours. The fermented soybean extract then is dried and ground into a fine powder.
- Table 1 is examples of preparation formulation of lOOg pain- relieving and anti-inflammatory preparation for preventing and treating thrombosis of the present invention, in which preperation method of the components has been described in Example 1.
- Toxicity test was performed on mice according to standard evaluation procedures for clinical trials on animals. Test mice were white mice, healthy, uniform in weight, tested with preparations CT1, CT2, CT3 and CT4 obtained from Example 2.
- mice are tested separately for subchronic toxicity based on the standard test during a 3-month period with preparations CT1, CT2, CT3 and CT4.
- the tested dosage is evaluated as 5g/kg/day continuously for 12 weeks.
- the test result showed that:
- liver function total bilirubin concentration, albumin and total cholesterol in rat blood
- liver cells There was no degradation of liver cells (AST and ALT activities in rat blood) compared to control group;
- Anticoagulant test of the preparations of the invention in a capsule form which used coagulant pattern by using lipopolysaccharit in rats was taken as below:
- the dosage of 1.62capsule/kg (equivalent to 03 times more than the expected dosage in the clinic) and has anticoagulant effect on coagulant pattern via LPS and also indicate the long-term effects as APTT(s) and APTT diseases- symptoms, compared to control group.
- a dosage of 0.54 capsule/kg tends to appear anti-chronic inflammatory effect in rats via granulomatous inflammation pattern to reduce the weight of granulomas, reduce the amount of inflammatory cells on granulomatous cortex.
- the results were shown in FIGs. 5 and 6 to compare with the result of the placebo control group (FIGs. 1 and 2) and it indicated that the result was significantly effective.
- - Preparations of CT1 and CT2 with the dosage of 1.62 capsule/kg/day (equivalent to 3 times more than the clinical dosage) (FIGs. 6 and 7), which have significant anti-chronic inflammatory effect in rats via granulomatous inflammation pattern.
- Example 4 The test of evaluating anti-inflammatory and treatment thrombosis
- Study subjects included 180 patients at the National Hospital of Traditional Medicine, were divided randomly 3 groups: A, B and C.
- the patients had symptoms of cervical pain, headache, numbness, dizzy, insomnia and Alzheimer.
- the study did not require patients to be hospitalized (except having the indication from doctors). In the case of hospitalization, patients will be followed and monitored until return the stable situation in accordance with the evaluation of researchers.
- Group 1 used placebo as control group.
- Group 2 used CT2 and CT3 received from the example 1 in turn.
- Group 3 used CT1 from the example 1.
- NDI scale based on the international questionnaires of evaluating patient life quality. - Evaluate the level of spastic muscles, radiculopathy, cervical syndrome, syndrome of vertebral artery before and after treatment.
- Group 1 has the rate of vertebral degeneration, disc herniation and others as 21.7%; 5% va 43.3% respectively; group 2 has these rates as 30%, 6.7%; va 41.7% respectively; and control group has the rates as 30%; 1.7%; va 50% respectively.
- the indexes of survival signs before treatment did not differ from from 03 groups.
- the average heart rate is 74.6 times/min
- the average of body temperature is 36.5°C
- average of systolic pulse pressure is 118.5
- average diastolic pulse pressure is 72.9 mmHg.
- the index of blood formulas before treatment on 03 groups are in normal range and almost did not have any significant differences (except the amount of lymphocytes in group 2 was higher than others).
- the average of red blood cells was 4,8G/dL
- average white blood cells was 7 G/L
- average platelets was 247.1 G/L
- average hemoglobin was 14.4 g/dL
- average hematocrit was 43%.
- White blood cells contain neutrophil, eosinophil, basophil, monocyte and lymphocyte which have the average as 55.5%, 3.6%, 0.99%, 7.7%, va 32.3% respectively.
- Cervical spine X-ray showed that abnormal images appeared in all 03 groups and accounted for a high rate.
- the images of narrowing joint spaces were found with 44.4% of total studied patients. This rate in study group 2 was 31.7% which was lower than n group 1 (48.3%) and in the control group (53.3%).
- the images of degenerative bones under cartilages appeared with 56.7% of total samples and did not have any significant differences among 03 groups.
- 80.6% of total study patients appeared the images of spinal stenosis and this rate was equivalent in all 03 groups.
- Vertebral degenerative sites often appeared at C4, C5 and C6 with 91%, 93.4% and 79.5% respectively on total study samples.
- C3 and C7 had the rate of vertebral degeneration were 59.6% and 45,8% respectively. It is so rare to appear at C2 (1.2%).
- the images of vertebral degeneration were equivalent at C2, C3, C4 and C5.
- C6 and C7 were different from others: the images of vertebral degeneration at C6 in 03 groups as 56.4%, 32.1%, and 49.1% respectively.
- other abnormalities in the vertebral X-ray was 27.8% and they were equivalent to 03 groups.
- the characteristics of MRI images did have some differences among 03 study groups. Generally, the percentage of disc herniation was 95%, the rate of disc degeneration images was 68.7%; the rate of disc injury was 97.8% and other was 55.6%. The sites of disc injury were equivalent to vertebral sites which had degeneration X-ray images. The disc sites at C3-C4, C4-C5 and C5-C6 had the highest injury rate as 73.9%, 92.6% and 80.1% in turn. At C2-C3 and C6-C7, the injury rate was low as 0.6% and 19.9% respectively.
- 03 study groups did not have any significant differences from each other for each factor of evaluating activity limitation level caused by cervical pains at each following point.
- group B and group C showed better improvement than the control group, but the difference was not that clear and the difference was not inferior to each other.
- the rate of none/mild limitation ( ⁇ 14point) at after 1 -month termination of 03 groups were 86,7%, 90% and 95%, respectively.
- the result is to evaluate the ability of cervical exercise.
- the cervical syndrome did not appear at the point before treatment (TO) and only appeared in 01 case at 15-day time point after treatment (Tl).
- TO point before treatment
- Tl 15-day time point after treatment
- T2 and T3 time point there were not any cases with cervical syndrome.
- the syndrome of vertebral artery appeared in 97.8% of patients at TO and reduced slightly after treatment; 46.7% of patients after 1 -month treatment (T3).
- Group A reduced less and 59.3% cases had this syndrome at T3.
- group B and group C had the rates at T3 point as 42.1% and 39.3%.
- the NDI reducing efficiency is the rate of reducing total NDI points at Tl, T2 and T3, compared with NDI point at TO [(Total point at Tx - Total points at T) xl 00/total points at TO] Other results are calculated in accordance with the number of cases at Tl, T2 and T3, compared to at
- Pain-relieving and anti-inflammatory preparations for preventing and treating thrombosis using natural medicinal herds of the present invention is combined by traditional medicine and modern medical knowledge to create high effects in pain relief, anti-inflammatory, thrombotic prevention and treatment, effects in the body through meridians according to the principles of traditional medicine, improves blood circulation, increases memory and prevents and reduces complications, pain relief, and anti-inflammatory, help to create a balanced treatment system.
- products additionally combine with the ingredients which have complication-reducing effects on brain, help to strengthen vessels, improve neurotransmitters and enhance memory and other pain-relieving ingredients and anti-chronic inflammatory ingredients in the cases of neurological syndrome and clogging blood vessels at neck area.
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Abstract
The present invention relates to preparation pain-relieving rooted from natural herbs for preventing and treating thrombosis, wherein the preparation comprises the blood activating component including at least three of group medicinal herbs comprises: Nattokinase, Dangshen, Szechuan lovage, Safflower, Fo-Ti, Dongquai, E Jiao, Chinese peony, Medicinal leech, Earthworm; the qi-blood tonifying and drug delivering component including at least one of the medicinal herbs comprising: Ginseng, Bai Zhu, Dangshen, Jujube fruit, Notoginseng, Mongolian milkvetch, Liquorice, Peach blossom and Cinnamon; the bone tonifying and pain- relieving component including at least seven in the medicinal herbs comprising: Hardy rubber tree, Qian Nian Jian, Chinese Tinospora, Tu Fu-ling, Du Huo, Qiang Huo, Ox Knee, Large cocklebur, Ivy Tree, Strychnine tree, Fang Feng, Sang Ji Sheng, Gentian Root, St Paul's-wort, Gang Zhu, Tu Fu-ling, Fu-ling, Chinese foxglove, Chinese Foxglove, Ginger, Xi Xin, Bai Zhi and White willow, other species belonging to Salix; the neurotransmitters including at least one in the medicinal herbs comprising: Velvet bean and Stag's-hom clubmoss; and excipients. The preparation of the present invention is effective for treatment of thrombosis, anti-inflammatory, prevention and pain-relief.
Description
PAIN-RELIEVING AND ANTI-INFLAMMATORY PREPARATION FOR
PREVENTING AND TREATING THROMBOSIS
Field of the Invention
The present invention relates to the field of traditional medicines, in particular to a pain-relieving anti-inflammatory preparation for preventing and treating thrombosis using natural medicinal herds.
Prior Art
Coagulation is a naturally occurring process that allows blood cells to clump together and form a blood clot or blood clot. This process is beneficial, especially when the body is damaged causing bleeding. And although most natural clots can dissolve on their own without complications, there are situations where they can be life-threatening, such as those that form in arteries, which can clog the arteiy and cut off oxygen supply to part of the body. Consequently, it can cause heart attacks, damage and/or destroy blood vessel walls (infarction), cause death of heart tissue in the patients. In the brain, a blood clot also blocks blood and oxygen from reaching the area it needs, which can lead to senility and/or stroke.
The World Journal of Pharmaceutical Research, ISSN 2277-7105, has published Plant as anticogulant / antithrombotic agent, in which a number of plants may contain the active ingredients able to treat thrombosis and to prevent from the formation of thrombosis, including: Sesame bark ( Sesamum indicum ) extract, Indian rhododendron ( Melastoma malabathricum ) leaf extract, Flame lily (Gloriosa superb) leaf extract, Water hyacinth ( Eichhornia crassipe ) leaf extract, Brazilian Orchid Tree ( Bauhinia forficate) leaf extract, Physic nut {Jatropha curcas) leaf and fruit extract, Horse-Tail Creeper ( Porana volubilis) flower and leaf extract, Synclisia scabrida whole plant extract, Sponge seaweed ( Codium fragil). Devil Weed (Sargassum horeri), Garlic (. Allium sativum ) extract, Onion
{Allium cepa ) extract, Turmeric (Curcuma longa) radix and rhizome extract, Black myrobalan (T erminalia belerica) fruit extract , etc.
In particular, according to the mechanism of Traditional Medicine, the thrombosis clogging vessels in any body parts leads to pains and inflammation of surrounding areas for a long-term period. As a result, the treatment of common pain and inflammation needs to combine with antithrombotic factors in order to totally treat and reduce the causes of pains and inflammation. Conversely, if antithrombotic drugs have additionally anti-inflammatory effects and reduce pains, it will effectively treat the secondary symptoms.
Apart from the symptoms of pains, secondary inflammations as mentioned above, there are other forms of pains which may be caused by bacterial infection, viral infection, tissues/cells injuries, bone and joint degeneration, etc. Currently, modem medicines with reducing pains, anti-inflammatory effects mainly use NS AID group or Corticoid group in the severe pains. The weaknesses of these dmgs are that they cause side effects on stomach and other undesirable side effects such as kidney degeneration with long-term uses. On the other hand, pain and inflammation which are caused by thrombosis is chronic and it is required for long term medication that additionally make the side effects worse.
Traditional medicine has the advantage of being derived from herbs, so it is very safe for patients, rarely having side effects like modem medicine. However, each remedy only works either to treat thrombosis or to reduce pain or anti- inflammation. The releasing pain, if any, may only be caused by improvement of thrombosis, but not because of directly treatment of both pains and inflammations at the same time. These traditional remedies are effective for pain relief, active blood activity which are intended for joint and bone diseases and mainly with lower joints such as wrists, knee joints because these remedies have ingredients such as Ox Knee or Large-leaf gentian, etc, which intend to lead the medicines downstream to lower body parts.
However, in modem medical clinical, the proportion of shoulder pain and neck pain due to modern habits such as less activity, more indoor working has been
creasing: degenerative neck vertebrae, disc degeneration, nerve and blood vessel clog which lead in circulation problems and pains. The numbers of patients who get the problems with thrombosis leading in serious cardiovascular complications which mainly occur in chest, neck and head areas have been increasing, too.
Therefore, there is still a need for research and development of medicines that can combine pain relief and anti-inflammatory treatment with thrombotic prevention and treatment with enhanced synergistic effects, and not only have effects on with lower osteoarthritis such as wrist joints, knee joints and also works well on upper body parts such as shoulders, nape (back neck), neck and head, as well as helps increase drug compliance in patients by a fact that the patients do not take many medicines at the same time.
Sumary of the Invention
In order to resolve the above mentioned problems, the present invention particularly relates to a pain-relieving and anti-inflammatory preparation for preventing and treating thrombosis, wherein the preparation comprises components as follows: the blood activating component; the qi-blood tonifying and drug delivering component; the bone tonifying and pain-relieving component; and excipients.
The blood activating component comprises at least three of the medicinal herbs comprising: Nattokinase, Dangshen ( Radix Salviae militiorrhizae), Szechuan lovage ( Rhizoma Ligustici wa wallichii), Safflower (Carthamus tinctorius), Fo-Ti (Fallopia multiflora), Dongquai ( Radix Angelicae sinensis ), E Jiao ( Colta Asini), Chinese peony (. Radix Paeoniae lactiflorae ), Medicinal leech ( Hirudo medicinalis), Earthworm ( Pheretima aspergilum) or medicinal herbs with equivalent effects. Preferably, the blood activating component comprises at least
four of these medicinal herbs. Most preferably, the blood activating component comprises at least five of these medicinal herbs.
In one embodiment of the present invention, the blood activating component comprises: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech.
In another embodiment of the present invention, the blood activating component comprises: Nattokinase, Szechuan lovage, Dongquai, Chinese peony and Medicinal leech.
The qi-blood tonifying and drug delivering component comprises at least one of the medicinal herbs comprising: Ginseng ( Panax gingseng), Bai Zhu (Atractylodes macrocephala) , Dangshen ( Radix Codonnopsis ), Jujube fruit (Fructus Ziziphi Jujubae) ( Fructus Ziziphi jujubae ), Notoginseng (. Radix Panax pseudoginseng), Mongolian milkvetch {Astragalus membranaceus ), Liquorice {Radix et Rhizoma Glycyrrhizae), Peach blossom {Prunus persicd) and Cinnamon {Ramulus Cinnamomi) or medicinal herbs with equivalent effects. Preferably, the blood activating component comprises at least two or three of these medicinal herbs. Most preferably, the blood activating component comprises at least four or five of these medicinal herbs.
In still one embodiment of the present invention, the qi-blood tonifying and drug delivering component comprises: Dangshen, Notoginseng, Liquorice, Peach blossom and Cinnamon. Dangshen and Cinnamon’s properties are light, flexible and effective in leading medicine upwards in the body. Using Dangshen and Cinnamon instead of Ginseng and Cortex Cinnamomi that have been used in the existing remedies, combined with White willow, Peach blossom and Notoginseng makes the preparation of the present invention gain unexpected effects, compared with existing remedies including neck traditional remedies, in effectively delivering the active components to the upper body parts such as head, shoulder, back neck, neck, leading in more effective treatment of secondary or primary inflammatory pains.
The bone tonifying and pain-relieving component comprises at least seven in the medicinal herbs comprising: Hardy rubber tree ( Cortex Eucommiae), Qian Nian Jian (Rhizoma Homalomenae) , Chinese Tinospora (Tinospora sinensis ), Tu Fu-ling (Smilax glabra), Du Huo ( Radix Angelicae pubescentis ), Qiang Huo (Notopterygium incisium), Ox Knee ( Radix Achyranthis bidentatae ), Large cocklebur (Xanthium strumarium ), Ivy Tree (Schefflera heptaphylla), Strychnine tree (Strychnos nux - vomica), Fang Feng ( Radix Saposhnikoviae divaricatae ), Sang Ji Sheng ( Herba Taxilli ), Gentian Root {Radix Gentianae), St Paul’s-wort (Sigesbeckia orientalis), Cang Zhu (Atractylodes lancea), Tu Fu-ling {Smilax glabra), Fu-ling ( Poria ), Chinese foxglove {Radix Rehmanniae glutinosae), Chinese Foxglove (Rehmannia glutinosa), Ginger (Zingiber officinale), Xi Xin {Radix et Rhizoma Asari), Bai Zhi (Angelica dahurica) and White willow (Salix alba), and other species belonging to Salix genus or medicinal herbs with equivalent effects. Preferably, the blood activating component comprises at least eight or nine of these medicinal herbs. Most preferably, the blood activating component comprises at least ten of these medicinal herbs.
In a further embodiment of the present invention, the bone tonifying and pain- relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove and White willow.
In another more embodiment of the present invention, the bone tonifying and pain-relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove.
In still another more embodiment of the present invention, the bone tonifying and pain-relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Fu-ling, Chinese foxglove, Xi Xin and White willow.
In one embodiment of the present invention, the preparation of the present invention further comprises neurotransmitters. Said neurotransmitters comprises at least one in the medicinal herbs comprising: Velvet bean (Semen Mucuna pruriens) and Stag’s-hom clubmoss (Lycopodium clavatum L .) or medicinal herbs with
equivalent effects. Preferably, said neurotransmitters comprises Velvet bean and Stag’s-hom clubmoss.
In another embodiment of the present invention, the preparation of the present invention comprises components in percentage by weight as follows: the blood activating component: 20-50%, preferably 25-45%, most preferably 30-40%, in a particular embodiment the blood activating component is of 30%; the qi-blood tonifying and drug delivering component: 2-40%, preferably 5- 30%, most preferably 10-20%, in a particular embodiment the qi-blood tonifying and drug delivering component is of 10%; the bone tonifying and pain-relieving component: 5-40 preferably 10-30%, most preferably 15-20%, in a particular embodiment the bone tonifying and pain- relieving component is of 30%; neurotransmitters: 0-35%, preferably 5-30%, most preferably 10-25%; in a particular embodiment neurotransmitters is of 25%; and excipients, q.s. to 100%.
In one embodiment of the present invention, the blood activating component comprises in percentage by weight:
Nattokinase: 25-95%, preferably 30-90%, most preferably 35-85%;
Medicinal leech, Earthworm*: 0-25%, preferably 2-22%, most preferably 5-
20%;
Dangshen, Szechuan lovage, Safflower*: 0.1-10%; preferably 0.2-8%, most preferably 0.5-6%;
Fo-Ti, Dongquai, E Jiao*: 2-30%, preferably 7-27%, most preferably 10- 25%; and
Chinese peony: 0-30%, preferably 7-27%, most preferably 10-25%.
*At least one of said medicinal herbs.
In one embodiment of the present invention, the qi-blood tonifying and drug delivering component comprises in percentage by weight:
Ginseng, Bai Zhu, Dangshen*: 20-60%, preferably 25-55%, most preferably 30-50%;
Jujube fruit, Notoginseng, Mongolian milkvetch*: 0-35%, preferably 5-30%, most preferably 7-27%;
Liquorice: 0-20%, preferably 5-17%, most preferably 7-15%;
Peach blossom: 0-35%, preferably 5-30%, most preferably 7-27%; and
Cinnamon: 0-45%, preferably 5-42%, most preferably 7-40%.
*At least one of said medicinal herbs.
In one embodiment of the present invention, the bone tonifying and pain- relieving component comprises comprises in percentage by weight:
The extract of White willow (Salix alba) and other species belonging to Salix*: 0-80%, preferably 25-65%, most preferably 30-60%;
Hardy rubber tree, Qian Nian Jian*: 1-20%, preferably 5-17%, most preferably 7-15%,
Chinese Tinospora, Tu Fu-ling, Du Huo, Qiang Huo*: 0.5-20%, preferably 1- 17%, most preferably 2-12%;
Ox Knee, Large cocklebur, Ivy Tree*: 0.5-20%, preferably 1-17%, most preferably 2-12%;
Strychnine tree, Fang Feng*: 0.5-20%, preferably 1-17%, most preferably 2-
12%;
Sang Ji Sheng: 0.5-20%, preferably 1-17%, most preferably 2-12%;
Gentian Root, St Paul’s-wort, Cang Zhu*: 0.5-20%, preferably 1-17%, most preferably 2-12%;
Tu Fu-ling, Fu-ling*: 0-18%, preferably 5-17%, most preferably 7-15%;
Chinese foxglove, Chinese Foxglove*: 5-20%, preferably 7-175, most preferably 9-15%; and
Ginger, Xi Xin, Bai Zhi*: 0-15%, preferably 0.2-12%, most preferably 0.5-
10%.
*At least one of said medicinal herbs.
In one embodiment of the present invention, the neurotransmitters comprises in percentage by weight:
Extract of Stag’s-hom clubmoss: 0-70%, preferably 20-65%, most preferably 25-60%; and
Velvet bean: 0-70%, preferably 20-65%, most preferably 25-60%.
In one still other embodiment, the preparation of the present invention further comprises excipients of natri benzoat, magie stearat and talc powder q.s. to 100% of the preparation weight.
Brief Description of the Drawings
FIG.l is the micro-histological image of the control group in the pharmacological study cua Example 1, which showed a wide centeral degenerative region with multiple degenerative polymorphonuclear leukocytes.
FIG.2 is the micro-histological image of the control group in the anti inflammatory study, which showed that the degenerative wall had many fibroblasts and polymorphonuclear leukocytes and lymphocytes.
FIG.3 is the micro-histological image of the orally methylprednisolon group with concentration of 10 mg/kg, which showed the much appearance of polymorphonuclear leukocytes in the internal area.
FIG.4 is the micro-histological image of the orally methylprednisolon group with concentration of 10 mg/kg, which showed the less appearance of polymorphonuclear leukocytes in the external area.
FIG.5 is the anatomic image of rat tissue after oral administration of the preparation of a low dose of 0.54 capsule/kg/day. The image showed that the
necrotic areas contained many polymorphonuclear leukocytes, but do not contain any lymphocytes after 10-day oral administration of CT1.
FIG.6 is the anatomic image of rat tissue afer oral administration of the preparation of a low dose of 0.54 capsule/kg/day. The image showed that the peripheral areas contain additionally many polymorphonuclear leukocytes and lymphocytes after 10-day oral administration of CT1.
FIG.7 is the anatomic image of rat tissue after oral administration of the preparation with a high dose of 1.62 capsule/kg/day. The image showed that the necrotic areas contain many polymorphonuclear leukocytes and contain few lymphocyte after 10-day oral administration of CT1.
FIG.8 is the anatomic image of rat tissue after oral administration of the preparation with a high dose of 1.62 capsule/kg/day. The image showed that that the peripheral areas appear additionally many polymorphonuclear leukocytes and lymphocytes after 10-day oral administration of CT1.
Detailed Description of the Invention
The present invention will be described below in detail with the preferred embodiments specific illustrative examples. These embodiments and examples are given for the purpose of well understanding the present invention but not to limit the scope of protection of the present invention.
In this specification, all weights are represented in percentage by weight, when referring to a percentage range of a particular component, for example ‘in a/the range of A to B%’ means to include both A and B values and any values between A and B. In addition, when referring to a particular percentage value, for example ‘C%’ is defined as a range around the C value, which is usually 10% greater or less. This ensures that the variants of the present invention are realized clearly and within the tolerances for mixing multiple components together.
The blood activating component of the present invention enhances blood circulation, reduces the formation of thrombosis, this component is in the range of 20-50%, preferably 25-45%, most preferably 30-40% by weight of the preparation.
In some particular embodiments, the amount of the blood activating component in the preparation of the present invention is 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50% by weight of the preparation.
The blood activating component comprises at least three, preferably four, and most preferably five of the medicinal herbs in percentage by weight as follows: Nattokinase, Medicinal leech, Earthworm, Dangshen, Szechuan lovage, Safflower, Fo-Ti, Dongquai, E Jiao and Chinese peony.
In some preferable embodiments, an amount of Nattokinase in the blood activating component is in a range of 25-95%, preferably 30-90% and most preferably of 35-85% by weight of the blood activating component. In some particular embodiments, an amount of Nattokinase in the blood activating component is 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or 95% by weight of the blood activating component. In the most preferable embodiment, Nattokinase used most preferably is 60% by weight of the blood activating component.
In some preferable embodiments, an amount of Medicinal leech and/or Earthworm in the blood activating component is in a range of 0-25%, preferably 2- 22% and most preferably 5-20% by weight of the blood activating component. In some particular embodiments, an amount of Medicinal leech and or Earthworm in the blood activating component is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25% by weight of the blood activating component. In the most preferable embodiment, an amount of Medicinal leech used is most preferably 20% by weight of the blood activating component.
In some preferable embodiments, an amount of Dangshen, Szechuan lovage, Safflower, or a combination of at least two of them in the blood activating component is in a range of 0.1-10%, preferably 0.2-8% and most preferably 0.5- 6% by weight of the blood activating component. In some particular embodiments, an amount of Dangshen, Szechuan lovage, Safflower, or a combination of at least two of them in the blood activating component is 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10% by weight of the blood activating component. In the most preferable
embodiment, an amount of Dongquai used is most preferably 2% by weight of the blood activating component.
In some preferable embodiments, an amount of Fo-Ti, Dongquai, E Jiao, or a combination of at least two of them in the blood activating component is in a range of 2-30%, preferably 7-27% and most preferably 10-25% by weight of the blood activating component. In some particular embodiments, an amount of Fo-Ti, Dongquai, E Jiao, or a combination of at least two of them in the blood activating component is 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or 30% by weight of the blood activating component. In the most preferable embodiment, an amount of Dongquai used is most preferably 20% by weight of the blood activating component.
In some preferable embodiments, an amount of Chinese peony in the blood activating component is in a range of 0-30%, preferably 7-27% and most preferably 10-25% by weight of the blood activating component. In some particular embodiments, an amount of Chinese peony in the blood activating component is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30% by weight of the blood activating component. In the most preferable embodiment, an amount of Chinese peony used is most preferably 20% by weight of the blood activating component.
The qi-blood tonifying and drug delivering component of the present invention enhances and tonifies qi-blood, leading the drugs, therefore this component increases therapeutic effect while enhancing the health of patients. The qi-blood tonifying and drug delivering component is in the range of 2-40%, preferably 5-30% and most preferably 10-20% by weight of the preparation. In some particular embodiments, an amount of the qi-blood tonifying and drug delivering component in the preparation of the present invention is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40% by weight of the preparation.
The qi-blood tonifying and drug delivering component of the present invention comprises at least one, preferably two or three and most preferably four
of the following medicinal herbs: Ginseng, Bai Zhu, Dangshen, Jujube fruit, Notoginseng, Mongolian milkvetch, Liquorice, Peach blossom and Cinnamon.
In some preferable embodiments, an amount of Ginseng, Bai Zhu, Dangshen or a combination of at least two of them used is in a range of 20-60%, preferably 25-55% and most preferably 30-50% by weight of the qi-blood tonifying and drug delivering component. In some particular embodiments, an amount of Ginseng, Bai Zhu, Dangshen or a combination of at least two of them in the qi-blood tonifying and drug delivering component is 20, 25, 30, 35, 40, 45, 50, 55 or 60% by weight of the qi-blood tonifying and drug delivering component. In the most preferable embodiment, an amount of Dangshen used is most preferably 30% by weight of the qi-blood tonifying and drug delivering component.
In some preferable embodiments, an amount of Jujube fruit, Notoginseng, Mongolian milkvetch or a combination of at least two of them used is in a range of 0-35%, preferably 5-30% and most preferably 7-27% by weight of the qi-blood tonifying and drug delivering component. In some particular embodiments, Jujube fruit, Notoginseng, Mongolian milkvetch or a combination of at least two of them in the qi-blood tonifying and drug delivering component is 0, 5, 10, 15, 20, 25, 30 or 35% by weight of the qi-blood tonifying and drug delivering component. In the most preferable embodiment, an amount of Notoginseng used is most preferably 25% by weight of the qi-blood tonifying and drug delivering component.
In some preferable embodiments, an amount of Liquorice used is in a range of 0-20%, preferably 5-17% and most preferably 7-15% by weight of the qi-blood tonifying and drug delivering component. In some particular embodiments, an amount of Liquorice in the qi-blood tonifying and drug delivering component is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% by weight of the qi-blood tonifying and drug delivering component. In the most preferable embodiment, an amount of Liquorice used is most preferably 15% by weight of the qi-blood tonifying and drug delivering component.
In some preferable embodiments, an amount of Peach blossom used is in a range of 0-35%, preferably 5-30% and most preferably 7-27% by weight of the qi-
blood tonifying and drug delivering component. In some particular embodiments, an amount of Peach blossom in the qi-blood tonifying and drug delivering component is 0, 0.5, 1, 5, 10, 15, 20, 25, 30 or 35% by weight of the qi-blood tonifying and drug delivering component. In the most preferable embodiment, an amount of Peach blossom used is most preferably 20% by weight of the qi-blood tonifying and drug delivering component.
In some preferable embodiments, an amount of Cinnamon used is in a range of 0-45%, preferably 5-42% and most preferably 7-40% by weight of the qi-blood tonifying and drug delivering component. In some particular embodiments, an amount of Cinnamon in the qi-blood tonifying and drug delivering component is 0, 5, 10, 15, 20, 25, 30, 35, 40 or 55% by weight of the qi-blood tonifying and drug delivering component. In the most preferable embodiment, an amount of Cinnamon used is most preferably 30% by weight of the qi-blood tonifying and drug delivering component.
Often diseases related to thrombosis often cause inflammation, bleeding in places where there is a blood clot in the vessel wall causing pain. The combination of ingredients for tonic and pain relief, combined with active ingredients, helps reduce circulation and especially protects the vessel wall, reduces inflammation.
The bone tonifying and pain-relieving component in combination with the blood activating component increases the effect of treating thrombosis. Commonly, thrombosis relating diseases often cause inflammation and bleeding in the internal vessel walls of thrombosis leading in pains. By using a combination of the bone tonifying and pain-relieving component and the blood activating component helps increasing blood circulation and especially protecting vessel walls, and reducing or preventing from inflammation. The bone tonifying and pain-relieving component in the preparation is in the range of 5-40% by weight of the preparation. In some preferable embodiments, the bone tonifying and pain-relieving component in the preparation of the present invention preferably is in a range of 10-30% by weight of the preparation, more preferably is is in a range of 15-20% by weight of the preparation. In some particular embodiments, the amount of the bone tonifying and
pain-relieving component in the preparation of the present invention is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40% by weight of the preparation.
The bone tonifying and pain-relieving component comprises at least seven, preferably eight or nine, most preferably ten of the following medicinal herbs: Extract of White willow, other species belonging to Salix, Hardy rubber tree, Qian Nian Jian, Chinese Tinospora, Tu Fu-ling, Du Huo, Qiang Huo, Ox Knee, Large cocklebur, Ivy Tree, Strychnine tree, Fang Feng, Sang Ji Sheng, Gentian Root, St Paul’s-wort, Cang Zhu, Tu Fu-ling, Fu-ling, Chinese foxglove, Chinese Foxglove, Ginger, Xi Xin and Bai Zhi.
In some preferable embodiments, an amount of White willow and/or other species belonging to Salix used is in a range of 0-80%, preferably 25-65% and most preferably 30-60% by weight of the bone tonifying and pain-relieving component. In some particular embodiments, an amount of White willow in the bone tonifying and pain-relieving component is 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 or 80% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of White willow used is most preferably 50% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Hardy rubber tree and/or Qian Nian Jian used is in a range of 1-20%, preferably 5-17% and most preferably 7- 15% by weight of the bone tonifying and pain-relieving component. In some particular embodiments, an amount of Hardy rubber tree in the bone tonifying and pain-relieving component is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Hardy rubber tree used is most preferably 12% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Chinese Tinospora, Tu Fu- ling, Du Huo, Qiang Huo or a combination of at least two of them used is in a range of 0.5-20%, preferably 1-17% and most preferably 2-12% by weight of the bone tonifying and pain-relieving component. In some particular embodiments, an
amount of Du Huo in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain- relieving component. In the most preferable embodiment, an amount of Du Huo used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Ox Knee, Large cocklebur, Ivy Tree or a combination of at least two of them used is in a range of 0.5-20%, preferably 1-17% and most preferably 2-12% by weight of the bone tonifying and pain-relieving component. In some particular embodiments, an amount of Ox Knee in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Ox Knee used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Fang Feng and/or Strychnine tree used is in a range of 0.5-20%, preferably 1-17% and most preferably 2-12% by weight of the bone tonifying and pain-relieving component. In some particular embodiments, an amount of Fang Feng in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Fang Feng used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Sang Ji Sheng is used in a range of 0.5-20%, preferably 1-17% by weight of the bone tonifying and pain- relieving component. In some particular embodiments, an amount of Sang Ji Sheng in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Sang Ji Sheng used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Gentian Root, St PauTs-wort, Cang Zhu or a combination of at least two of them used is in a range of 0.5-20%, preferably 1-17% by weight of the bone tonifying and pain-relieving component.
In some particular embodiments, an amount of Gentian Root in the bone tonifying and pain-relieving component is 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Gentian Root used is most preferably 10% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Fu-ling and/or Tu Fu-ling used is in a range of 0-18%, preferably 5-17% and most preferably 7-15% by weight of the bone tonifying and pain-relieving component. In some particular embodiments, an amount of Fu-ling in the bone tonifying and pain-relieving component is 0, 3, 5, 7, 9, 11, 13, 15, 17, 18 or 20% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Fu-ling used is most preferably 12% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Chinese foxglove and/or Chinese Foxglove used is in a range of 5-20%, preferably 5-17% and most preferably 7-15% by weight of the bone tonifying and pain-relieving component. In some particular embodiments, an amount of Chinese foxglove in the bone tonifying and pain-relieving component is 5, 10, 15, 17 or 20% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Chinese foxglove used is most preferably 12% by weight of the bone tonifying and pain-relieving component.
In some preferable embodiments, an amount of Ginger, Xi Xin, Bai Zhi or a combination of at least two of them used is in a range of 0-15%, preferably 0.2- 12% and most preferably 0.5-10% by weight of the bone tonifying and pain- relieving component. In some particular embodiments, an amount of Xi Xin in the bone tonifying and pain-relieving component is 0.1, 0.2, 0.5, 0.7, 1, 1.2, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10% by weight of the bone tonifying and pain-relieving component. In the most preferable embodiment, an amount of Xi Xin used is most preferably 6% by weight of the bone tonifying and pain-relieving component.
Neurotransmitters in the preparation of the present invention is for sedation, reducing symtoms of memory loss due to the embolism impact by thrombosis, helping to restore the nervous system damages. The neurotransmitters in the preparation of the present invention comprises Velvet bean and Stag’s-hom clubmoss, in the range of 0-35%, preferably 5-30%, most preferably 10-25% by weight of the preparation.
In some preferable embodiments, an amount of Velvet bean used is in a range of 0-70%, preferably 20-65%, and most preferably 25-60% by weight of the neurotransmitters. In some particular embodiments, an amount of Velvet bean in the neurotransmitters is 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or 70% by weight of the neurotransmitters. In the most preferable embodiment, an amount of Velvet bean used is most preferably 40% by weight of the neurotransmitters.
In some preferable embodiments, an amount of Stag’s-hom clubmoss used is in a range of 0-70%, preferably 20-65%, and most preferably 25-60% by weight of the neurotransmitters. In some particular embodiments, an amount of Velvet bean in the neurotransmitters is 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65 or 70% by weight of the neurotransmitters. In the most preferable embodiment, an amount of Velvet bean used is most preferably 60% by weight of the neurotransmitters.
In addition, the preparation of the present invention further comprises excipients including natri benzoat, talc, magie stearat. These excipients play the roles of fillers, preservatives or flavor enhancers. These excipients can be substituted by other ones, depending on the purposes of use in the preparation, thus known by a person in the field. Such excipients are known and available for sale.
According to another preferalbe embodiment, the preparation of the present invention consists of a bone tonifying and pain-relieving component including at least Hardy mbber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove and White willow.
It has supprisingly been found that with the combination of White willow (bone tonifying and pain-relieving effect) together with Dangshen and Cinnamon (drug delivering effect) and Notoginseng and Peach blossom (blood tonifying
effect), the preparation of the present invention has acchieved unexpected effects of pain-relieving and anti-inflammatory on the regions of head, neck, shoulder and upper arm, i.e the upper body parts. Dangshen, Cinnamon and Peach blossom own light and flexible behaviors, thus make them the ability of delivering drugs veiy well to the upper body parts. This is a very special effect of the preparation of the present invention, since almost existing remedies are effective to the lower joints (wrists, knee joints, etc.) but not or less to the upper body parts (head, neck, shoulder and upper arm) as the the preparation of the present invention is.
According to another preferalbe embodiment, the preparation of the present invention consists of components the blood activating component including at least: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech; and the bone tonifying and pain-relieving component including at least: Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove; and neurotransmitters including: Velvet bean and Stag’s-hom clubmoss.
It has supprisingly been found that with the combination of Medicinal leech (blood activating effect) and Stag’s-hom clubmoss (bone tonifying and pain- relieving effect), the preparation of the present invention has strong effect on treating thrombosis and reducing complications in the brain.
According to another preferalbe embodiment, the preparation of the present invention consists of the bone tonifying and pain-relieving component including at least: Hardy mbber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove and White willow; the blood activating component including at least: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech; the bone tonifying and pain-relieving component including at least: Hardy mbber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove; and the neurotransmitters including: Velvet bean and Stag’s-hom clubmoss.
It has supprisingly been found that the combination of components White willow, Medicinal leech, Stag’s-hom clubmoss together with Dangshen, Notoginseng and Peach blossom allows the preparation of the present invention to have pain-relieving and anti-inflammatory effect while its effect of preventing and
treating thrombosis is much better than using individual remedy for each particular effect. This is especially beneficial because the symtoms of pain caused by inflammation and thrombosis often come together, and the preparation of the present invention will help the patients’use of the medicines more conveniently and effectively.
These are the creative advantages of the preparation of the present invention.
The preparation of the present invention is useful for pain-relieving and anti inflammatory and for preventing and treating thrombosis. The preparation, therefore, are effective in treating musculoskeletal and joints diseases, pains of neck, shoulder, back neck due to cervical degenerative disease, herniated disc leading in compression of nerves and blood vessels, obstructing cerebral circulation. The preparation is also useful for treatmenting and/or protecting cerebral vessels because of vasodilation, protecting blood vessel walls, supporting treatment of complications caused by strokes.
Examples
Example 1. Preparing the components
The components are prepared according to know techniques in the field. That is, each component can be prepared individually, then mixed at defined proportions; or all components can be prepared at the same time at defined proportions; or in any known proper techniques. Below is an example of preparing the components together at the same time, wherein their proportions are referenced in Example 2.
- Medicinal leech is prepared by selecting large and strong leeches, then soaking them with alcohol to their death. The dead leaches are picked out, washed, then cut open, turned the entire intestine out. Then they are rinsed with saline water for several times, following by boiled up, cu tinto pieces and then dried. After that, the dried Medicinal leeches are grinded into powder. Then said powder is sifted using 0.2mm sieve to obtain Medicinal leach powders.
- Each component of Chinese peony, Dongquai, Szechuan lovage, Dangshen, Notoginseng, Liquorice, Peach blossom, Cinnamon, White willow, Hardy rubber
tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Fu-ling, Chinese foxglove, Xi Xin, Stag’s-horn clubmoss is collected, processed according to pharmacopoeia’s guides, washed and put into pot for being extracted 3 times, each for 3 hours. The extract is filtered and evaporated until it becomes a concentrated form with moisture content of about 20%. The obtained concentrate can be added with nipagin and nipasol that have been dissolved in an enough amout of 96% ethanol, while stirring. Then the obtained material is poured into moulds to obtain concentrated extract cakes having moisture content of 20%. These cakes are cut into thin slices of about 3-5cm thickness. The thin slices are preaded over a tray and put in a static oven, dried at a temperature of about 85 °C to dry. The dried product is let to cool in the room temperature then finely grinded with a hammer mill, then sifted through a 0.2mm sieve to obtain powders, each has a moisture content of about 5%.
- Nattokinase extract is prepared by soaking soybeean seeds, peeling off the skin, riped up, adding Baccillus natto, then incubating at 42°C for 5 hours. The fermented soybean extract then is dried and ground into a fine powder.
- Velvet bean is collected, washed, dried, then finely ground, sifted through a 0.2mm sieve to obtain a fine powder.
Example 2. Preparation of pain-relieving and anti-inflammatory preparation and treatment thrombosis
In Table 1 below is examples of preparation formulation of lOOg pain- relieving and anti-inflammatory preparation for preventing and treating thrombosis of the present invention, in which preperation method of the components has been described in Example 1.
Example 3. Toxicity test a) Acute toxicity test:
Toxicity test was performed on mice according to standard evaluation procedures for clinical trials on animals. Test mice were white mice, healthy, uniform in weight, tested with preparations CT1, CT2, CT3 and CT4 obtained from Example 2.
Dosage is evaluated independently for each preparation with a dosage from 1 capsule/kg (0.786g - 0.913g/capsule) body weight to 50 capsules/kg body weight, equivalent to the highest dose of 0.25mg/10g, 3 times for 24 hours. No dead mice were reported, no abnormal symptoms appeared within 72 hours after taking a
single dosage of the preparation and during 7 days. Therefore, all 4 preparations are not toxic to mice with doses up to 0.25mg/g. b) Subchronic toxicity test
Mice are tested separately for subchronic toxicity based on the standard test during a 3-month period with preparations CT1, CT2, CT3 and CT4. The tested dosage is evaluated as 5g/kg/day continuously for 12 weeks. The test result showed that:
- The tested doses did not harmfully affect the general status, level of increasing mice weights compared to the control group (use placebo);
- There was no change in the test result on hematopoietic function (amount of red blood cells, hemoglobin content, hematocrit, average volume of red blood cells, amount of white blood cells and leukocyte formulas) compared to the control group;
- There was no change in the test results on the evaluation of liver function (total bilirubin concentration, albumin and total cholesterol in rat blood) compared to the control group;
- There was no degradation of liver cells (AST and ALT activities in rat blood) compared to control group;
- There was no change in the test result on creatinine in rat blood after a 12- day period using drugs continuously, compared to the control group;
- There was no harmful affect on appearances when observing macro-organs of white rats compared to the control group;
- The structure of micro-histological of rat livers did not appear to cause any damages after a 12-week period using the preparations, compared to the control group;
- The structure of micro-histological of rat kidneys had mild damage after a 12-week period using preparations, compared to the control group. c) Pharmacological test
To evaluate the anticoagulant effect of the preparations of the invention in a capsule form in coagulant pattern by using thrombin and fibrin injection in rabbits, the following dosages were used:
- Dosages of 0.36 capsule/kg (equivalent to expected dosage in the clinic) and 1.08 capsule/kg (equivalent to 03 times more than the expected dosage), which have anticoagulant effect on coagulant pattern by using thrombin and fibrin injection in rabbits and show the long-term effect of APTT(s) and APTT disease- symptom;
- Dosages of 0.36 capsule/kg (equivalent to expected dosage in the clinic) and 1.08 capsule/kg (equivalent to 3 times more than the expected dosage), which have reduced fibrin (blood clots) via the decrease of D-Dimer concentration, compared to pattern group.
Anticoagulant test of the preparations of the invention in a capsule form, which used coagulant pattern by using lipopolysaccharit in rats was taken as below:
- The dosage of 0.54capsule/kg (equivalent to the expected dosage in the clinic): did not appear to have any anticoagulant effect with the coagulant pattern via LPS in rats;
- The dosage of 1.62capsule/kg (equivalent to 03 times more than the expected dosage in the clinic) and has anticoagulant effect on coagulant pattern via LPS and also indicate the long-term effects as APTT(s) and APTT diseases- symptoms, compared to control group.
The test results of the anti-inflammatory effect of the drug on rats of chronic inflammation by implantation of asbestos fibers gave the following results:
- A dosage of 0.54 capsule/kg (equivalent to the expected dosage in the clinic) tends to appear anti-chronic inflammatory effect in rats via granulomatous inflammation pattern to reduce the weight of granulomas, reduce the amount of inflammatory cells on granulomatous cortex. The results were shown in FIGs. 5 and 6 to compare with the result of the placebo control group (FIGs. 1 and 2) and it indicated that the result was significantly effective.
- Preparations of CT1 and CT2 with the dosage of 1.62 capsule/kg/day (equivalent to 3 times more than the clinical dosage) (FIGs. 6 and 7), which have significant anti-chronic inflammatory effect in rats via granulomatous inflammation pattern. This effect is equivalent to methylprednisolon with the dosage of lOmg/kg (FIGs. 3 and 4). The test formulas do not appear to have any changes on uric acid index, blood glucose during the entire using drug process. For the DC formulas, the indexes of anti-inflammatory effects are much lower than CT1, CT2 and CT3.
Example 4. The test of evaluating anti-inflammatory and treatment thrombosis
To evaluate the ability of the preparation for anti-inflammatory, pain-relieving and thrombosis therapies, trials on volunteers were conducted. The test was conducted randomly, double-blinded and had comparison between the parallel dosage groups.
Study subjects included 180 patients at the National Hospital of Traditional Medicine, were divided randomly 3 groups: A, B and C. The patients had symptoms of cervical pain, headache, numbness, dizzy, insomnia and Alzheimer. The study did not require patients to be hospitalized (except having the indication from doctors). In the case of hospitalization, patients will be followed and monitored until return the stable situation in accordance with the evaluation of researchers.
Group 1 (A) used placebo as control group. Group 2 (B) used CT2 and CT3 received from the example 1 in turn. Group 3 (C) used CT1 from the example 1.
For each group: to compare the effective and safety variables at each evaluating point (after 15 days with the T1 treatment, after 1 month with the T2 treatment, after terminating the T3 treatment) and compare them with the time point before TO treatment; use the equivalent inspection for different data as below:
- Quantitative (NDI scale, clinical point scale): based on the international questionnaires of evaluating patient life quality.
- Evaluate the level of spastic muscles, radiculopathy, cervical syndrome, syndrome of vertebral artery before and after treatment.
- The result of inspection and report via p index.
- Evaluate the VAS scale of 03 patient groups at treatment points.
- Evaluate the exercise limitation level of 03 patient groups before and after treatment.
Table 2.
The result is shown in accordance with frequency and percentage (%) (except they are marked as TB±DLC: average ± standard deviation)
Three study groups did not differ from the ages and the average age of the study group 1 is 60.1±12.4 age, the study group 2 with 59.4±12.2 age and the control group are 58.5±12.9 age.
Medical history of cervical syndrome, disc herniation and other diseases are equivalent in 03 study groups. Group 1 has the rate of vertebral degeneration, disc herniation and others as 21.7%; 5% va 43.3% respectively; group 2 has these rates
as 30%, 6.7%; va 41.7% respectively; and control group has the rates as 30%; 1.7%; va 50% respectively.
Three study groups did not differ from the weight, height, BMI index and overweight rate. The averages of weight and height in 03 groups are 57.2 kg va 158.7 cm respectively. BMI indexes before treatment of 03 groups as 23; 22.7 and 22.4 kg/m2 respectively. Overweight rates of 03 groups were 46.7%; 43.3% and 40.7%.
The indexes of survival signs before treatment did not differ from from 03 groups. Generally, the average heart rate is 74.6 times/min, the average of body temperature is 36.5°C, average of systolic pulse pressure is 118.5 and
average diastolic pulse pressure is 72.9 mmHg.
The result was shown in accordance with average ± standard deviation.
The index of blood formulas before treatment on 03 groups are in normal range and almost did not have any significant differences (except the amount of lymphocytes in group 2 was higher than others). For 03 groups, the average of red blood cells was 4,8G/dL, average white blood cells was 7 G/L, average platelets was 247.1 G/L, average hemoglobin was 14.4 g/dL, average hematocrit was 43%. White blood cells contain neutrophil, eosinophil, basophil, monocyte and lymphocyte which have the average as 55.5%, 3.6%, 0.99%, 7.7%, va 32.3% respectively.
Similarily, chemical blood index before treatment did not have any differences (except the rates of lymphocyte and cholesterol concentration). The average of AST, ALT in liver as 30.4 and 45.9U/L, GGT index was 35.8U/L, total bilirubin was 18mmol/L, creatinine was 70.9mmol/L, albumin was 38.6g/L, total cholesterol was 5.1mmol/L and glucoza was 5.7mmol/L.
The result is shown in accordance with frequency and percentage (%)
The characteristics of CXR before treatment showed that there were few cases with abnormal situations. Generally, 02 cases had big cardiac silhouette, 01 case had degenerative central artery and other 03 cases had abnormal signs on straight CXR. Moreover, the abnormal cases were evenly separated in 03 study groups.
Cervical spine X-ray showed that abnormal images appeared in all 03 groups and accounted for a high rate. The images of narrowing joint spaces were found with 44.4% of total studied patients. This rate in study group 2 was 31.7% which was lower than n group 1 (48.3%) and in the control group (53.3%). The images of degenerative bones under cartilages appeared with 56.7% of total samples and did not have any significant differences among 03 groups. 80.6% of total study patients appeared the images of spinal stenosis and this rate was equivalent in all 03 groups. Vertebral degenerative sites often appeared at C4, C5 and C6 with 91%, 93.4% and 79.5% respectively on total study samples. At C3 and C7 had the rate of vertebral degeneration were 59.6% and 45,8% respectively. It is so rare to appear at C2 (1.2%). In all 03 groups, the images of vertebral degeneration were equivalent at C2, C3, C4 and C5. Specifically, C6 and C7 were different from others: the images of vertebral degeneration at C6 in 03 groups as 56.4%, 32.1%, and 49.1% respectively. Moreover, other abnormalities in the vertebral X-ray was 27.8% and they were equivalent to 03 groups.
The characteristics of MRI images did have some differences among 03 study groups. Generally, the percentage of disc herniation was 95%, the rate of disc degeneration images was 68.7%; the rate of disc injury was 97.8% and other was 55.6%. The sites of disc injury were equivalent to vertebral sites which had degeneration X-ray images. The disc sites at C3-C4, C4-C5 and C5-C6 had the
highest injury rate as 73.9%, 92.6% and 80.1% in turn. At C2-C3 and C6-C7, the injury rate was low as 0.6% and 19.9% respectively.
The results after the test are showed as from Table 5 to Table 26 as below.
Table 5
Progress of exercise limitation level in daily routine: pain intensity with the time points on patients with cervical syndromes
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 6
Progress of exercise limitation level in daily routine: personal activities with the following time points
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 7
Progress of exercise limitation level in daily routine: lifting stuffs with the following time points
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 9
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 10
Progress of exercise limitation level in daily routine: ability to concentrate with the following time points
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 11
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 12.
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 v.s. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 13
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 14
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 15
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Generally, 03 study groups did not have any significant differences from each other for each factor of evaluating activity limitation level caused by cervical pains at each following point. In general, in terms of restricted daily activities, group B and group C showed better improvement than the control group, but the difference was not that clear and the difference was not inferior to each other. The rate of none/mild limitation (<14point) at after 1 -month termination of 03 groups were 86,7%, 90% and 95%, respectively. Some aspects of limited assessment have differences between the 3 groups but only appear in T2 and T3, eg personal activities, headaches and work.
The result of evaluating the pain level based on the VAS scale
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
The pain points based on the VAS scale of 03 study groups were not significantly different at the time before treatment (TO), but over time of follow-up there was a difference in the three groups. Specifically, at T3 (after 1 -month treatment), group B had the rate of no pains or mild pains was 90%, group A was 78.3% while group C was 70%.
The result is to evaluate the ability of cervical exercise.
Table 17
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 18
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 19
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 20
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 21
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 22
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Table 23
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
Generally, evaluation of cervical exercise limitation level with the following time points had a slight deviation among 03 study groups. Almost indexes have the improvement in both group B and group C but did not any significant differences. Regarding the progress of cervical exercise limitation in the following points showed that there were not any significant differences among 03 groups. After 1- month treatment, the cases passed no limitation of less limitation in 03 groups as 93.3%, 91.7% and 95% respectively.
The result of evaluating spastic muscles, radiculopathy, cervical syndrome and syndrome of vertebral artery
Table 24
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
The situation of spastic muscles appeared on almost patients before treatment (TO), this rate reduced slightly after treatment, 52.4% patients had spastic muscles after 1 -month treatment (T3). There were significant differences among 03 study groups. After 1 -month treatment (T3), group A had 64.8% patients who get spastic muscles, group B had 57.1% while group C had only 35.7%.
Regarding radiculopathy, before treatment (TO) this syndrome appeared with 97.8% of the number of patients and reduced slightly in the following time while it had only 49.1% number of patients after 1 -month treatment. Otherwise, there were not any significant differences in 03 groups. At the point after 1 -month treatment (T3), the control group had 50% cases which got spastic muscles whereas the rates in group B and group C as 54.4% and 42.9%, respectively.
The cervical syndrome did not appear at the point before treatment (TO) and only appeared in 01 case at 15-day time point after treatment (Tl). For the control group, at T2 and T3 time point, there were not any cases with cervical syndrome.
The syndrome of vertebral artery appeared in 97.8% of patients at TO and reduced slightly after treatment; 46.7% of patients after 1 -month treatment (T3). Group A reduced less and 59.3% cases had this syndrome at T3. Moreover, group B and group C had the rates at T3 point as 42.1% and 39.3%.
Adaptation of treatment
The results are showed under frequency and percentage.
P values are compared at Tl, T2, T3 vs. TO: *** < 0.001 < ** < 0.01 < * < 0.05
NDI: Neck Disability Index
Total points of clinical facilities were equivalent on all 03 groups at TO with the average point was 15.4 points. Otherwise, the decrease of clinical facilities points in 02 groups was better than n control group. At T3 (after 1 -month termination of treatment), total points of clinical facilities on 03 groups were 5.1, 4.3 and 3.3 points.
The NDI deviations at Tl, T2 and T3 were different from at TO. Group A reduced less (-9.7 point), while group B and group C reduced more (13.1 points).
The NDI reducing efficiency is the rate of reducing total NDI points at Tl, T2 and T3, compared with NDI point at TO [(Total point at Tx - Total points at T) xl 00/total points at TO] Other results are calculated in accordance with the number of cases at Tl, T2 and T3, compared to at
TO.
The results are showed under frequency and percentage. KXD: inconclusive; TB±DLC: average ± standard deviation
Avantages of the present invention
Pain-relieving and anti-inflammatory preparations for preventing and treating thrombosis using natural medicinal herds of the present invention is combined by traditional medicine and modern medical knowledge to create high effects in pain relief, anti-inflammatory, thrombotic prevention and treatment, effects in the body through meridians according to the principles of traditional medicine, improves blood circulation, increases memory and prevents and reduces complications, pain relief, and anti-inflammatory, help to create a balanced treatment system.
The combination of components Medicinal leech, Nattokinase, White willow in accordance with with the Chinese, Japanese traditional medicine and Vietnam
traditional medicine, the inventors created effective preparations that have been demonstrated under modem aspects and conception. This is a new way to improve the effects of the traditional remedies under modem medicine aspects, thus contribute to improve the humanbeing healthcare.
Using extract of White willow to enhance the effects of the pain-relieving anti-inflammatory the cases of chronic inflammation, which combine mild and flexible ingredients as leading ingredients including Dangshen (Radix Salviae militiorrhizae) substitutes Ginseng (Panax Ginseng), Cinnamon (Ramulus Cinnamomi) substitutes Cinnamon (Cortex Cinnamomi) with the addition of Notoginseng (Radix Panax pseudoginseng), Peach blossom (Prunus persica) which have blood-replenishing effect, blood-activating effect; Peach blossom (Pmnus persica) has mild effect and use as a leading ingredients (leading upwards). As a result, products do not have any combined effects to lead ingredients downwards to some parts as knee or hand joints whereas they have effects on treating the upper parts of the body as shoulder, neck and head.
Apart from other products in the market at this time, products additionally combine with the ingredients which have complication-reducing effects on brain, help to strengthen vessels, improve neurotransmitters and enhance memory and other pain-relieving ingredients and anti-chronic inflammatory ingredients in the cases of neurological syndrome and clogging blood vessels at neck area.
Claims
1. A pain-relieving and anti-inflammatory preparation for preventing and treating thrombosis wherein the preparation comprises: the blood activating component including at least three of group medicinal herbs comprises: Nattokinase, Dangshen, Szechuan lovage, Safflower, Fo-Ti, Dongquai, E Jiao, Chinese peony, Medicinal leech, Earthworm; the qi-blood tonifying and drug delivering component including at least one of the medicinal herbs comprising: Ginseng, Bai Zhu, Dangshen, Jujube fruit, Notoginseng, Mongolian milkvetch, Liquorice, Peach blossom and Cinnamon; the bone tonifying and pain-relieving component including at least seven in the medicinal herbs comprising: Hardy rubber tree, Qian Nian Jian, Chinese Tinospora, Tu Fu-ling, Du Huo, Qiang Huo, Ox Knee, Large cocklebur, Ivy Tree, Strychnine tree, Fang Feng, Sang Ji Sheng, Gentian Root, St Paul’s-wort, Cang Zhu, Tu Fu-ling, Fu-ling, Chinese foxglove, Chinese Foxglove, Ginger, Xi Xin, Bai Zhi and White willow, other species belonging to Salix; and excipients.
2. The preparation according to claim 1, wherein the preparation further comprises neurotransmitters including at least one in the medicinal herbs comprising: Velvet bean and Stag’s-hom clubmoss.
3. The preparation according to any preceeding claims, wherein its components in percentage by weight are as follows: the blood activating component: 20-50%; the qi-blood tonifying and drug delivering component: 2-40%; the bone tonifying and pain-relieving component: 5-40%; neurotransmitters: 0-35%; and excipients, q.s. to 100%.
4. The preparation according to claim 3, wherein its components in percentage by weight are as follows:
the blood activating component: 25-45%; the qi-blood tonifying and drug delivering component: 5-30%; the bone tonifying and pain-relieving component: 10-30%; neurotransmitters: 5-30; and excipients, q.s. to 100%.
5. The preparation according to claim 3, wherein its components in percentage by weight are as follows: the blood activating component: 30-40%; the qi-blood tonifying and drug delivering component: 10-20%; the bone tonifying and pain-relieving component: 15-20%; neurotransmitters: 10-25%; and excipients, q.s. to 100%.
6. The preparation according to any preceeding claims, wherein the bone tonifying and pain-relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove and White willow.
7. The preparation according to any of claims 1-3, wherein: the blood activating component comprises: Nattokinase, Szechuan lovage, Dongquai, Medicinal leech; the bone tonifying and pain-relieving component comprises Hardy rubber tree, Du Huo, Ox Knee, Fang Feng, Sang Ji Sheng, Gentian Root, Chinese foxglove; and neurotransmitters comprises: Velvet bean and Stag’s-hom clubmoss.
8. The preparation according any of claims 1-3, wherein the blood activating component comprises components in percentage by weight as follows:
Nattokinase: 25-95, preferably 30-90, most preferably 35-85;
Medicinal leech: 0-25, preferably 2-22, most preferably 5-20;
Szechuan lovage: 0.1-10, preferably 0.2-8, most preferably 0.5-6;
Dongquai: 2-30, preferably 7-27, most preferably 10-25; and Chinese peony: 0-30, preferably 7-27, most preferably 10-25.
9. The preparation according any of claims 1-3, wherein the qi-blood tonifying and drug delivering component comprises components in percentage by weight as follows:
Dangshen: 20-60, preferably 25-55, most preferably 30-50;
Notoginseng: 0-35, preferably 5-30, most preferably 7-27;
Liquorice: 0-20, preferably 5-17, most preferably 7-15;
Peach blossom: 0-35, preferably 5-30, most preferably 7-27; and Cinnamon: 0-45, preferably 5-42, most preferably 7-40.
10. The preparation according any of claims 1-3, wherein the bone tonifying and pain-relieving component comprises components in percentage by weight as follows:
Extract of White willow: 0-80, preferably 25-65, most preferably 30-60;
Hardy rubber tree: 1-20, preferably 5-17, most preferably 7-15;
Du Huo: 0.5-20, preferably 1-17, most preferably 2-12;
Ox Knee: 0.5-20, preferably 1-17, most preferably 2-12;
Fang Feng: 0.5-20, preferably 1-17, most preferably 2-12;
Sang Ji Sheng: 0.5-20, preferably 1-17, most preferably 2-12;
Gentian Root: 0.5-20, preferably 1-17, most preferably 2-12;
Fu-ling: 0-18, preferably 5-17, most preferably 7-15;
Chinese foxglove: 5-20, preferably 7-17, most preferably 9-15; and Xi Xin: 0-15, preferably 0.2-12, most preferably 0.5-10.
11. The preparation according to claim 2 or 3, wherein neurotransmitters comprise components in percentage by weight as follows:
Extract of Stag’s-hom clubmoss: 0-70, preferably 30-65, most preferably 35- 60; and
Velvet bean: 0-70, preferably 30-65, most preferably 35-60.
12. The preparation according to any of preceeding claims, wherein the excipients are natri benzoat, magie stearat and talc powder.
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ANONYMOUS: "Second-class pharmaceutical products | Chinese medicine: Kakkonto extract tablet Kracie [Kracie Product: 4987045049224 (TS03-U)]", November 2011 (2011-11-01), JP, pages 1 - 2, XP009531118, Retrieved from the Internet <URL:https://www.kracie.co.jp/products/pdf/4987045049224.pdf> * |
CILIA ROBERTO, LAGUNA JANETH, CASSANI ERICA, CEREDA EMANUELE, POZZI NICOLÒ G., ISAIAS IOANNIS U., CONTIN MANUELA, BARICHELLA MICHE: "ClinicalTrials.gov identifier: : Mucuna pruriens in Parkinson disease - A double-blind, randomized, controlled, crossover study", NEUROLOGY, LIPPINCOTT WILLIAMS & WILKINS , PHILADELPHIA, US, vol. 89, no. 5, 1 August 2017 (2017-08-01), US, pages 432 - 438, XP055853776, ISSN: 0028-3878, DOI: 10.1212/WNL.0000000000004175 * |
LI XIN, KANG MINGQIN, MA NINGNING, PANG TAN, ZHANG YANJUN, JIN HUA, YANG ZHEN, SONG LILI: "Identification and Analysis of Chemical Constituents and Rat Serum Metabolites in Lycopodium clavatum Using UPLC-Q-TOF/MS Combined with Multiple Data-Processing Approaches", EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE, OXFORD UNIVERSITY PRESS, US, vol. 2019, 2 July 2019 (2019-07-02), US, pages 1 - 8, XP055853775, ISSN: 1741-427X, DOI: 10.1155/2019/5165029 * |
See also references of EP4142756A4 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2022272314A1 (en) * | 2021-06-21 | 2022-12-29 | Sunstar Joint Stock Company | Medicine composition for treatment of bone and joint diseases originated from medicinal materials and the process for producing thereof |
CN113876657A (en) * | 2021-10-29 | 2022-01-04 | 柳州两面针股份有限公司 | Application of bauhinia extract in oral care product |
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EP4142756A1 (en) | 2023-03-08 |
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