CA2851947C - Use of extracts from filipendula for the treatment and prophylaxis of chronic pain conditions - Google Patents
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Abstract
The invention relates to the use of extracts from Filipendula for the treatment or prophylaxis of chronic pain conditions that have no identifiable organic causes.
Description
Doc. No.: 106-84 CA/PCT
Patent USE OF EXTRACTS FROM FILIPENDULA FOR THE TREATMENT AND
PROPHYLAXIS OF CHRONIC PAIN CONDITIONS
The present invention relates to the use of extracts from Filipendula for the treatment or prophylaxis of chronic pain without identifiable organic causes.
Chronic pain is more or less severe pain, which can affect one or more body regions and which lasts more than three months. Different processes can result in chronic pain (e.g. trauma, nerve damages, previous diseases or psychological factors), for which reason the symptoms of chronic pain are allocated to different indication areas (e.g. ICD-10 F45 õSomatoform Disorders", G43 õMigraine", G44 õOther Headache Syndromes", R51 õHeadache", R52 õPain, not elsewhere classified", M79.7 õFibromyalgia" R20.2 õParesthesia of the Skin", K58 õIrritable Bowel Syndrome", N94.3 õPremenstrual Complaints"). Chronic pain that is affected by this patent is only such in which no acute organic reasons for pain can be detected.
Chronic pain is clearly different from acute pain, since acute pain has a clear physiological function, namely avoiding further harmful impact on the corresponding tissue or the complete organism. Acute pain is induced by an acute stimulus (e.g.
temperature, pressure, injury, infection), is usually locally restricted to the affected site, is perceived as "sharp" and leads to a protection and avoidance reaction that should prevent further harmful impact. As soon as the impairment is over, also the pain disappears.
This physiological function is not present in chronic pain. The pain is not connected with an acute danger of a physiological impairment. Often, chronic pain is also less locally directed and perceived as rather "vague" and located deeper in the tissue. Chronic pain does not disappear. Hyperalgesia is a typical symptom of chronic pain, where pain caused by a similar stimulus is perceived much stronger than would normally be the case. Another example is allodynia, wherein a stimulus is perceived as painful, which normally does not cause pain.
Doc. No.: 106-84 CA/PCT
Patent Acute and chronic pain can also mechanically be distinguished well. Acute pain is caused by a stimulus of the nociceptive nerve endings (either directly or via receptors) and is processed as an action potential via the spinal cord and the brain.
This leads to clear activation of nerves that afterwards go back to the initial state. When the peripheral stimulus triggering is prevented, also the pain can be prevented.
Additionally, substances in the central nervous system can influence the pain processing and thereby cause analgesic perceptions.
In chronic pain different stimuli of the nerve system occur. Presently it is presumed that dysregulation of the nerve system e.g. a loss of inhibition of the NMDA
receptor and defective processing of pain processes in the brain are involved in chronic pain (Villman and Becker 2007; Neuroscientist; 13 (6); 594-615 / Woolf and Salter 2000, Science;
288; 1765-1768). Additionally, learn and psychosocial processes are involved in pain perception. This leads as a complex and multifactorial system to a continuous pain perception, for which in many cases no physical cause is detected. Since not only "typical" processes of pain processing are involved, neither analgesic substances that prevent the peripheral conduction of the stimuli (e.g. lidocaine), nor several centrally active analgesics have a long-term therapeutic benefit (Mello and Dickenson 2008;
British Journal of Anaesthesia; 101 (1); 8-16 / Hucho and Levine 2007; Neuron;
55; 365-376). Additionally, such substances (e.g. opioids) often have a problematic spectrum of side effects.
In contrast, in many chronic pain disorders, psychoactive medicaments such as e.g. pregabalin, ketamine or milnaciprane are used in individual cases, of which the effects are however limited (Lawson 2008; Drug Discovery Today; 13 (7-8); 333-Hauser et al 2009; JAMA; 301 (2); 198-209 / Sud et al. 2008; European Journal of Pharmacology; 588; 217-231). Therefore, there are no generally effective standard treatments available for chronic pain. Additionally, the discussed psychoactive substances are often contraindicated due to their neurological side effects.
Patent USE OF EXTRACTS FROM FILIPENDULA FOR THE TREATMENT AND
PROPHYLAXIS OF CHRONIC PAIN CONDITIONS
The present invention relates to the use of extracts from Filipendula for the treatment or prophylaxis of chronic pain without identifiable organic causes.
Chronic pain is more or less severe pain, which can affect one or more body regions and which lasts more than three months. Different processes can result in chronic pain (e.g. trauma, nerve damages, previous diseases or psychological factors), for which reason the symptoms of chronic pain are allocated to different indication areas (e.g. ICD-10 F45 õSomatoform Disorders", G43 õMigraine", G44 õOther Headache Syndromes", R51 õHeadache", R52 õPain, not elsewhere classified", M79.7 õFibromyalgia" R20.2 õParesthesia of the Skin", K58 õIrritable Bowel Syndrome", N94.3 õPremenstrual Complaints"). Chronic pain that is affected by this patent is only such in which no acute organic reasons for pain can be detected.
Chronic pain is clearly different from acute pain, since acute pain has a clear physiological function, namely avoiding further harmful impact on the corresponding tissue or the complete organism. Acute pain is induced by an acute stimulus (e.g.
temperature, pressure, injury, infection), is usually locally restricted to the affected site, is perceived as "sharp" and leads to a protection and avoidance reaction that should prevent further harmful impact. As soon as the impairment is over, also the pain disappears.
This physiological function is not present in chronic pain. The pain is not connected with an acute danger of a physiological impairment. Often, chronic pain is also less locally directed and perceived as rather "vague" and located deeper in the tissue. Chronic pain does not disappear. Hyperalgesia is a typical symptom of chronic pain, where pain caused by a similar stimulus is perceived much stronger than would normally be the case. Another example is allodynia, wherein a stimulus is perceived as painful, which normally does not cause pain.
Doc. No.: 106-84 CA/PCT
Patent Acute and chronic pain can also mechanically be distinguished well. Acute pain is caused by a stimulus of the nociceptive nerve endings (either directly or via receptors) and is processed as an action potential via the spinal cord and the brain.
This leads to clear activation of nerves that afterwards go back to the initial state. When the peripheral stimulus triggering is prevented, also the pain can be prevented.
Additionally, substances in the central nervous system can influence the pain processing and thereby cause analgesic perceptions.
In chronic pain different stimuli of the nerve system occur. Presently it is presumed that dysregulation of the nerve system e.g. a loss of inhibition of the NMDA
receptor and defective processing of pain processes in the brain are involved in chronic pain (Villman and Becker 2007; Neuroscientist; 13 (6); 594-615 / Woolf and Salter 2000, Science;
288; 1765-1768). Additionally, learn and psychosocial processes are involved in pain perception. This leads as a complex and multifactorial system to a continuous pain perception, for which in many cases no physical cause is detected. Since not only "typical" processes of pain processing are involved, neither analgesic substances that prevent the peripheral conduction of the stimuli (e.g. lidocaine), nor several centrally active analgesics have a long-term therapeutic benefit (Mello and Dickenson 2008;
British Journal of Anaesthesia; 101 (1); 8-16 / Hucho and Levine 2007; Neuron;
55; 365-376). Additionally, such substances (e.g. opioids) often have a problematic spectrum of side effects.
In contrast, in many chronic pain disorders, psychoactive medicaments such as e.g. pregabalin, ketamine or milnaciprane are used in individual cases, of which the effects are however limited (Lawson 2008; Drug Discovery Today; 13 (7-8); 333-Hauser et al 2009; JAMA; 301 (2); 198-209 / Sud et al. 2008; European Journal of Pharmacology; 588; 217-231). Therefore, there are no generally effective standard treatments available for chronic pain. Additionally, the discussed psychoactive substances are often contraindicated due to their neurological side effects.
2 Doc. No.: 106-84 CA/PCT
Patent In many diseases with chronic pain without organic cause, stress is discussed as an important inducing or accompanying parameter. It is known that continuing stress is often accompanied by the symptoms of chronic pain and causes this also in animal experiments (Dina et al. 2009; Neuroscience; 160; 501-507 / Imbe et al 2006;
Frontiers in Bioscience; 11; 2179-2192 / Vidal and Jacob 1986; Annals New York academy of sciences; 73-81).
The object of the present invention is therefore to provide a means, which can effectively be used in the treatment of chronic pain without identifiably organic cause and which is substantially free of side effects.
This object is, according to the invention, solved by using extracts from Filipendula species, preferably of Filipendula ulmaria, for therapy and prophylaxis of chronic pain without identifiable organic causes, especially of chronic pain, which is caused by somatoform disorders, and of vulvodynia as well as of abdomen, jaw joint, other joint, extremities, neck, shoulder, back, lumber, pelvic or spinal pain which is not of rheumatic origin, as well as of chronic pain which is induced by irritable bowel syndrome or by premenstrual complaints, by fibromyalgia or by paresthesia of the skin or migraine, cluster headache, chronic paroxysmal hemicrania, vasomotoric headache, tension headache or chronic posttraumatic headache. Preferably, the above-ground parts of plants (foliage) are used.
Filipendula is classified in the family of the Rosaceae and includes according to the invention the following species: F. ulmaria, F. angustiloba, F. digitata, F. formosa, F. glaberrima, F. kamtschatica, F. kiraishiensis, F. multijuga, F.
occidentalis, F. palmata, F. purpurea, F. rufinervis, F. rubra, F. vestita und F. vulgaris (syn. F.
hexapetala). A
preferred Filipendula species is Filipendula ulmaria. A further preferred Filipendula species is Filipendula vulgaris. A further preferred Filipendula species is Filipendula purpurea. The distribution region of the preferred plant Filipendula a ulmaria includes the northern regions of Europe, America and Asia. The traditional medicinal uses can be found in the area of colds and rheumatoid diseases (as diseases which involve
Patent In many diseases with chronic pain without organic cause, stress is discussed as an important inducing or accompanying parameter. It is known that continuing stress is often accompanied by the symptoms of chronic pain and causes this also in animal experiments (Dina et al. 2009; Neuroscience; 160; 501-507 / Imbe et al 2006;
Frontiers in Bioscience; 11; 2179-2192 / Vidal and Jacob 1986; Annals New York academy of sciences; 73-81).
The object of the present invention is therefore to provide a means, which can effectively be used in the treatment of chronic pain without identifiably organic cause and which is substantially free of side effects.
This object is, according to the invention, solved by using extracts from Filipendula species, preferably of Filipendula ulmaria, for therapy and prophylaxis of chronic pain without identifiable organic causes, especially of chronic pain, which is caused by somatoform disorders, and of vulvodynia as well as of abdomen, jaw joint, other joint, extremities, neck, shoulder, back, lumber, pelvic or spinal pain which is not of rheumatic origin, as well as of chronic pain which is induced by irritable bowel syndrome or by premenstrual complaints, by fibromyalgia or by paresthesia of the skin or migraine, cluster headache, chronic paroxysmal hemicrania, vasomotoric headache, tension headache or chronic posttraumatic headache. Preferably, the above-ground parts of plants (foliage) are used.
Filipendula is classified in the family of the Rosaceae and includes according to the invention the following species: F. ulmaria, F. angustiloba, F. digitata, F. formosa, F. glaberrima, F. kamtschatica, F. kiraishiensis, F. multijuga, F.
occidentalis, F. palmata, F. purpurea, F. rufinervis, F. rubra, F. vestita und F. vulgaris (syn. F.
hexapetala). A
preferred Filipendula species is Filipendula ulmaria. A further preferred Filipendula species is Filipendula vulgaris. A further preferred Filipendula species is Filipendula purpurea. The distribution region of the preferred plant Filipendula a ulmaria includes the northern regions of Europe, America and Asia. The traditional medicinal uses can be found in the area of colds and rheumatoid diseases (as diseases which involve
3 Doc, No.: 106-84 CA/PCT
Patent inflammatory processes), wherein as medicinal substance both the flowers, as well as the dried above-ground parts of the flowering plant are used (foliage).
Filipendula ulmaria contains salicylic acid derivatives and is brought in connection with the development of aspirin. Aspirin belongs as a salicylic acid derivative in the group of non-steroidal anti-rheumatics (NSAIDs), of which the common working principle is the inhibition of Cyclooxygenase 1 and 2 (COX 1 and 2). By the inhibition of the COX
enzymes, the inflammatory cascade is inhibited, since the cyclooxygenases produced the inflammatory mediating prostaglandins from arachidonic acid.
Prostaglandins are next to the actual inflammation also involved in the mediation of pain caused by inflammation, for which reason NSAIDs are also used in acute, inflammation-mediated pain (Brune 2004; Rheumatology; 43 (Supp1.1; i16-i20) / Wallace 2007; British Journal of Pharmacology; 152; 421-428).
It was now surprisingly found that extracts from Filipendula are effective in animal models for non-inflammatory chronic pain, which suggests their therapeutic usefulness in chronic pain without identifiable organic causes. Such an effect has not yet been described for Filipendula extracts and was not to be expected on the pharmacological and clinical effects which were until now known for Filipendula.
To prepare the extracts from Filipendula which are used according to the present invention, the dried and ground plant material is extracted with an organic solvent or water or a mixture of one or more organic solvents and/or water at a temperature between 10 C and 100 C. The extracted plant material is separated from the extract solution, e.g. by filtration, and optionally again extracted with a solvent according to the first step and again separated from the extract solution. The thereby obtained extract solutions are combined, evaporated and dried.
Preferred organic solvents for the extraction are alcohols or ketones, preferably ethanol or acetone and mixtures thereof with water. Especially preferred are mixtures of ethanol and water in a weight ratio of 20/80 to 80/20 (20 wt.% to 80 wt.%), preferably 50/50 to 70/30 (50 wt.% to 70 wt.%), as well as water. Useful extraction methods are
Patent inflammatory processes), wherein as medicinal substance both the flowers, as well as the dried above-ground parts of the flowering plant are used (foliage).
Filipendula ulmaria contains salicylic acid derivatives and is brought in connection with the development of aspirin. Aspirin belongs as a salicylic acid derivative in the group of non-steroidal anti-rheumatics (NSAIDs), of which the common working principle is the inhibition of Cyclooxygenase 1 and 2 (COX 1 and 2). By the inhibition of the COX
enzymes, the inflammatory cascade is inhibited, since the cyclooxygenases produced the inflammatory mediating prostaglandins from arachidonic acid.
Prostaglandins are next to the actual inflammation also involved in the mediation of pain caused by inflammation, for which reason NSAIDs are also used in acute, inflammation-mediated pain (Brune 2004; Rheumatology; 43 (Supp1.1; i16-i20) / Wallace 2007; British Journal of Pharmacology; 152; 421-428).
It was now surprisingly found that extracts from Filipendula are effective in animal models for non-inflammatory chronic pain, which suggests their therapeutic usefulness in chronic pain without identifiable organic causes. Such an effect has not yet been described for Filipendula extracts and was not to be expected on the pharmacological and clinical effects which were until now known for Filipendula.
To prepare the extracts from Filipendula which are used according to the present invention, the dried and ground plant material is extracted with an organic solvent or water or a mixture of one or more organic solvents and/or water at a temperature between 10 C and 100 C. The extracted plant material is separated from the extract solution, e.g. by filtration, and optionally again extracted with a solvent according to the first step and again separated from the extract solution. The thereby obtained extract solutions are combined, evaporated and dried.
Preferred organic solvents for the extraction are alcohols or ketones, preferably ethanol or acetone and mixtures thereof with water. Especially preferred are mixtures of ethanol and water in a weight ratio of 20/80 to 80/20 (20 wt.% to 80 wt.%), preferably 50/50 to 70/30 (50 wt.% to 70 wt.%), as well as water. Useful extraction methods are
4 Doc. No. 106-84 CA/PCT Patent e.g. maceration or percolation (see European Pharmacopeia, Edition 6.0).
Drying is possible by methods known per se, such as e.g. freeze drying or drying in vacuum at room temperature or elevated temperature. To increase the concentration of selected ingredients, further concentration steps can be performed, such as e.g. liquid-liquid distribution with e.g. 1-butanol/water or ethyl acetate/water, adsorption-desorption on ion exchangers, Sephadex LH20, Diaion HP20 and other resins, or chromatographic separations over RP 18, silica gel, etc.
In a preferred embodiment, a kind of the grinded foliage (above-ground parts) of the desired Filipendula species is stirred with five to ten parts 50 wt.% to 70 wt.%
ethanol during 1/2 hour to 3 hours at 50 C to 60 C. The extracted plant material is separated from the extract solution by filtration and again stirred with five to ten parts 50 wt.% to 70 wt.% ethanol during 1/2 hour to 3 hours at 50 C to 60 C and filtered. The combined filtrates from both extraction steps are freed from the ethanol in a vacuum at 40 C to 60 C and freeze dried and/or dried in vacuum at 40 C to 60 C in a drying cabinet.
The extracts can preferably orally be administered in form of drops, powders, granules, tablets, coated tablets or capsules. However, also a parenteral administration in the form of an injection solution or a topical application in form of creams, ointments, suppositories, patches or similar formulations is possible.
For the preparation of tablets, the extract is mixed with excipients that are pharmaceutically acceptable and acceptable according to food law such as e.g.
lactose, cellulose, silicon dioxide, croscarmellose and magnesium stearate and pressed into tablets, that can optionally be provided with a suitable coating, e.g. of hydroxymethylpropyl cellulose, polyethylene glycol, dyes (e.g. titanium dioxide, iron oxide) and talcum.
Drying is possible by methods known per se, such as e.g. freeze drying or drying in vacuum at room temperature or elevated temperature. To increase the concentration of selected ingredients, further concentration steps can be performed, such as e.g. liquid-liquid distribution with e.g. 1-butanol/water or ethyl acetate/water, adsorption-desorption on ion exchangers, Sephadex LH20, Diaion HP20 and other resins, or chromatographic separations over RP 18, silica gel, etc.
In a preferred embodiment, a kind of the grinded foliage (above-ground parts) of the desired Filipendula species is stirred with five to ten parts 50 wt.% to 70 wt.%
ethanol during 1/2 hour to 3 hours at 50 C to 60 C. The extracted plant material is separated from the extract solution by filtration and again stirred with five to ten parts 50 wt.% to 70 wt.% ethanol during 1/2 hour to 3 hours at 50 C to 60 C and filtered. The combined filtrates from both extraction steps are freed from the ethanol in a vacuum at 40 C to 60 C and freeze dried and/or dried in vacuum at 40 C to 60 C in a drying cabinet.
The extracts can preferably orally be administered in form of drops, powders, granules, tablets, coated tablets or capsules. However, also a parenteral administration in the form of an injection solution or a topical application in form of creams, ointments, suppositories, patches or similar formulations is possible.
For the preparation of tablets, the extract is mixed with excipients that are pharmaceutically acceptable and acceptable according to food law such as e.g.
lactose, cellulose, silicon dioxide, croscarmellose and magnesium stearate and pressed into tablets, that can optionally be provided with a suitable coating, e.g. of hydroxymethylpropyl cellulose, polyethylene glycol, dyes (e.g. titanium dioxide, iron oxide) and talcum.
5 Doc. No.. 106-84 CA/PCT
Patent The extracts can also, optionally by adding excipients that are pharmaceutically acceptable and acceptable according to food law such as e.g. stabilizers, fillers etc., be filled in capsules.
The dosing is such that 5 to 2000 mg per day, preferably 10 to 1000 mg, especially preferred 60 to 600 mg extract are administered.
The extracts as well as the products made from them can be used both as drug products and as food products. Food products are here to be understood as especially dietetic food products, food supplements such as "medical food" and "dietary supplements".
The effectiveness of the extracts from Filipendula is demonstrated by the experiments described below.
Pharmacological studies Swimming stress induced hyperalgesia:
The pain sensitivity of rats is tested on a hot plate. The licking of the food or jumping is considered as a pain reaction. The time until this reaction occurs is measured and used as a measure for the pain sensation. Swimming stress during three consecutive days (30 min each) results in a clear reduction of the pain threshold (hyperalgesia). This effect can be reversed by the treatment with extract from Filipendula ulmaria according to Example 1 or ketamine 5 mg/kg (reference substance).
Figure 1 shows the influence of extract from Filipendula ulmaria according to Example 1 on hyperalgesia induced by swimming stress. The base values of the reaction times on the hot plate at different days (1 and 4), as well as the times 30 and 60 minutes after the p.o. administration of solvent control, extract or reference substance at day 4 (arrow) are indicated.
Patent The extracts can also, optionally by adding excipients that are pharmaceutically acceptable and acceptable according to food law such as e.g. stabilizers, fillers etc., be filled in capsules.
The dosing is such that 5 to 2000 mg per day, preferably 10 to 1000 mg, especially preferred 60 to 600 mg extract are administered.
The extracts as well as the products made from them can be used both as drug products and as food products. Food products are here to be understood as especially dietetic food products, food supplements such as "medical food" and "dietary supplements".
The effectiveness of the extracts from Filipendula is demonstrated by the experiments described below.
Pharmacological studies Swimming stress induced hyperalgesia:
The pain sensitivity of rats is tested on a hot plate. The licking of the food or jumping is considered as a pain reaction. The time until this reaction occurs is measured and used as a measure for the pain sensation. Swimming stress during three consecutive days (30 min each) results in a clear reduction of the pain threshold (hyperalgesia). This effect can be reversed by the treatment with extract from Filipendula ulmaria according to Example 1 or ketamine 5 mg/kg (reference substance).
Figure 1 shows the influence of extract from Filipendula ulmaria according to Example 1 on hyperalgesia induced by swimming stress. The base values of the reaction times on the hot plate at different days (1 and 4), as well as the times 30 and 60 minutes after the p.o. administration of solvent control, extract or reference substance at day 4 (arrow) are indicated.
6 Doc. No. 106-84 CA/PCT Patent Glucocorticoid induced hyperalgesia:
Stress reactions are physiologically largely mediated by the release of glucocorticoids (Kolber et al. 2008; Stress; 11(5); 321-338). By administering corticosterone via drinking water during a time period of 14 days, a chronic stress situation is simulated in rats, which causes a hyperalgesia. This hyperalgesia is measured by an apparatus which determines the pain threshold when exercising an increasing pressure on a back paw. Here, the time until the paw is drawn away as a pain reaction is measured. At day 15, 6 measurements are performed over a time period of 8 hours (0, 1/2, 1, 2, 4, 8 hours) and the "Area under the Curve"
(AUC) is calculated on the basis thereof. As can be derived from Figure 2, the extract from Filipendula ulmaria according to Example 1 inhibits in all evaluated dosages the hyperalgesia induced by corticosterone.
Figure 2 shows the influence of extract from Filipendula ulmaria on hyperalgesia induced by corticosterone. Indicated is the "Area under the Curve" of the time course measurement curves. *: error probability p 5_ 0.05 Example 1: Extract from Filipendula ulmaria 600 g of finely ground foliage (above-ground parts) of Filipendula ulmaria are stirred twice with 4200 g 60 wt.% ethanol during 1 hour at 60 C, the suspension is subsequently drawn via a Fritte P4, the combined filtrates are freed from ethanol in vacuum at 60 C, the remaining aqueous residue frozen and lyophilized. The obtained solid is dried in vacuum at 40 C over P205 and KOH: 146.2 g (24.4%) dry extract.
Example 2: Tablets A dry extract from Filipendula ulmaria (extract according to Example 1) is mixed with excipients and pressed to tablets (tablet core = position 1 ¨ 6). The tablets are coated with a coating of hydroxypropyl methyl cellulose (position 7 ¨ 10).
Stress reactions are physiologically largely mediated by the release of glucocorticoids (Kolber et al. 2008; Stress; 11(5); 321-338). By administering corticosterone via drinking water during a time period of 14 days, a chronic stress situation is simulated in rats, which causes a hyperalgesia. This hyperalgesia is measured by an apparatus which determines the pain threshold when exercising an increasing pressure on a back paw. Here, the time until the paw is drawn away as a pain reaction is measured. At day 15, 6 measurements are performed over a time period of 8 hours (0, 1/2, 1, 2, 4, 8 hours) and the "Area under the Curve"
(AUC) is calculated on the basis thereof. As can be derived from Figure 2, the extract from Filipendula ulmaria according to Example 1 inhibits in all evaluated dosages the hyperalgesia induced by corticosterone.
Figure 2 shows the influence of extract from Filipendula ulmaria on hyperalgesia induced by corticosterone. Indicated is the "Area under the Curve" of the time course measurement curves. *: error probability p 5_ 0.05 Example 1: Extract from Filipendula ulmaria 600 g of finely ground foliage (above-ground parts) of Filipendula ulmaria are stirred twice with 4200 g 60 wt.% ethanol during 1 hour at 60 C, the suspension is subsequently drawn via a Fritte P4, the combined filtrates are freed from ethanol in vacuum at 60 C, the remaining aqueous residue frozen and lyophilized. The obtained solid is dried in vacuum at 40 C over P205 and KOH: 146.2 g (24.4%) dry extract.
Example 2: Tablets A dry extract from Filipendula ulmaria (extract according to Example 1) is mixed with excipients and pressed to tablets (tablet core = position 1 ¨ 6). The tablets are coated with a coating of hydroxypropyl methyl cellulose (position 7 ¨ 10).
7 Doc. No.: 106-84 CAIPCT Patent Component mg/tablet 1 Dry extract from Filipendula ulmaria 100.0 according to Example 1 2 Microcrystalline cellulose 117.0 3 Lactose monohydrate 58.0 4 Croscarmellose 15.0 Highly dispersed silicon dioxide 3.0 6 Magnesium stearate 6.0 7 Hydroxypropyl methyl cellulose 15.0
8 Polyethylene glycol 3.0
9 Talcum 1.0 Titanium dioxide 2.0
Claims (6)
1. Use of an extract from Filipendula for the treatment or prophylaxis of chronic pain, in which stimuli of the nerve system occur, wherein the extract is obtained by extraction with 50-70 wt.% ethanol, wherein the chronic pain is caused by at least one somatoform disorder selected from the group consisting of psychalgia, headache, back pain, chronic pain disorder with somatic and psychological factors, vulvodynia pain, abdomen pain, shoulder pain, back pain, lumber pain, spinal pain which is not of rheumatic origin, chronic pain induced by irritable bowel syndrome or by premenstrual complaints, chronic pain induced by paresthesia of the skin, chronic pain induced by cluster headache, chronic paroxysmal hemicrania, vasomotoric headache, tension headache, and chronic posttraumatic headache.
2. The use of the extract from Filipendula according to claim 1, wherein the Filipendula for production of the extract is selected from the group consisting of F. ulmaria, F. angustiloba, F. digitata, F. formosa, F. glaberrima, F.
kamtschatica, F. kiraishiensis, F. multijuga, F. occidentalis, F. palmata, F. purpurea, F.
rufinervis, F. rubra, F. vestita and F. vulgaris
kamtschatica, F. kiraishiensis, F. multijuga, F. occidentalis, F. palmata, F. purpurea, F.
rufinervis, F. rubra, F. vestita and F. vulgaris
3. The use of the extract from Filipendula according to claim 2, wherein Filipendula ulmaria is used as the Filipendula for production of the extract.
4. The use of the extract from Filipendula according to any one of claims 1 to 3, wherein the extract is made with above-ground parts of Filipendula.
5. The use of the extract from Filipendula according to any one of claims 1 to 4, wherein a drug or food product comprising the extract from Filipendula is used in the treatment or prophylaxis of the chronic pain.
6. The use of the extract from Filipendula according to claims 5, comprising use of pharmaceutically acceptable excipients.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| DE102011085413.4 | 2011-10-28 | ||
| DE102011085413A DE102011085413A1 (en) | 2011-10-28 | 2011-10-28 | Use of extracts from Filipendula for the treatment and prophylaxis of chronic pain conditions |
| PCT/EP2012/071031 WO2013060714A1 (en) | 2011-10-28 | 2012-10-24 | Use of extracts from filipendula for the treatment and prophylaxis of chronic pain conditions |
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| CA2851947A1 CA2851947A1 (en) | 2013-05-02 |
| CA2851947C true CA2851947C (en) | 2020-03-24 |
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| CA2851947A Active CA2851947C (en) | 2011-10-28 | 2012-10-24 | Use of extracts from filipendula for the treatment and prophylaxis of chronic pain conditions |
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| EP (1) | EP2780025B1 (en) |
| KR (1) | KR20140087018A (en) |
| CN (1) | CN104768562A (en) |
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| CA (1) | CA2851947C (en) |
| DE (1) | DE102011085413A1 (en) |
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| HU (1) | HUE026719T2 (en) |
| MX (1) | MX348397B (en) |
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| RU (1) | RU2608442C2 (en) |
| UA (1) | UA110735C2 (en) |
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| CN104383167A (en) * | 2014-10-24 | 2015-03-04 | 辛海滨 | Chinese and western compound medicinal tablet for treating migraine |
| CN104383146A (en) * | 2014-12-02 | 2015-03-04 | 莫海棠 | Drug for fumigating neck |
| PL412214A1 (en) | 2015-05-04 | 2016-11-07 | Biovico Spółka Z Ograniczoną Odpowiedzialnością | Composition of plants with anti-inflammatory, antiallergic and/or antiasthmatic properties and its applications |
| KR102444911B1 (en) * | 2019-07-12 | 2022-09-21 | 코스맥스바이오 주식회사 | Composition for preventing or treating muscle-related diseases, improvement of muscular function or exercise performance comprising an extract of wild edible greens as an active ingredient |
| KR102256821B1 (en) * | 2019-07-17 | 2021-05-27 | 재단법인 경기도경제과학진흥원 | Composition for Improving Wrinkle Using an Extract of Filipendula palmata |
| KR102221265B1 (en) * | 2019-10-10 | 2021-03-04 | 한국과학기술연구원 | Food compositions and pharmaceutical compositions containing Filipendula glaberrima extract for lowering blood cholesterol levels and for improving atherosclerosis |
| KR102259214B1 (en) * | 2020-11-30 | 2021-05-31 | 한경훈 | Kimchi seasoning using functional substances and method for producing Kimchi using the same |
| CN113024494B (en) * | 2021-03-15 | 2022-07-12 | 西安交通大学 | Phenanthrene compound, preparation method and application |
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| EP0507035A1 (en) * | 1991-04-03 | 1992-10-07 | Synthelabo | Meadowsweet extracts, preparation and use thereof |
| RU2149009C1 (en) * | 1996-11-27 | 2000-05-20 | Гаврилин Олег Николаевич | Agent for treatment of trophic ulcers |
| US7033618B2 (en) * | 1999-02-26 | 2006-04-25 | Rutgers University, The State University Of New Jersey | Methods of administering gaultherin-containing compositions |
| US6528076B2 (en) * | 2001-07-06 | 2003-03-04 | Magic Herb Corp. | Topical compositions and methods for treating pain |
| RU2210380C1 (en) * | 2002-05-16 | 2003-08-20 | Горбачёва Анастасия Викторовна | Anti-inflammatory agent |
| MXPA04002940A (en) * | 2004-03-26 | 2005-09-28 | Velez Rivera Hector | Phyto-composition for the treatment of articular diseases. |
| DE202005005557U1 (en) * | 2005-04-08 | 2005-06-16 | Leibner, Sieglinde | Oil or balm for treating rheumatism, gout, sciatica, joint pain and back pain comprises a St John's wort extract, an arnica extract and essential oils |
| US20070134195A1 (en) * | 2005-12-13 | 2007-06-14 | Ward Aurelia L | Topical Analgesic for Sensitive Skin |
| RU2308284C1 (en) * | 2006-02-14 | 2007-10-20 | Виктор Владимирович Кузнечиков | Method for production of immunostimulating agent from dropwort filipendula ulmaria (l) |
| RU2430750C2 (en) * | 2006-02-21 | 2011-10-10 | Айрм Ллк | Methods and compositions for treating hyperalgesia |
| US20080014272A1 (en) * | 2006-07-11 | 2008-01-17 | Phil Skolnick | Compositions and Methods for Treatment of Chronic Pain Conditions |
| KR20110122448A (en) * | 2010-05-04 | 2011-11-10 | 주식회사 코리아나화장품 | Cosmetic composition comprising the extract of filipendula formosa as active ingredient |
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2011
- 2011-10-28 DE DE102011085413A patent/DE102011085413A1/en not_active Withdrawn
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2012
- 2012-10-24 CN CN201280052840.1A patent/CN104768562A/en active Pending
- 2012-10-24 AU AU2012330478A patent/AU2012330478B2/en active Active
- 2012-10-24 CA CA2851947A patent/CA2851947C/en active Active
- 2012-10-24 HU HUE12775513A patent/HUE026719T2/en unknown
- 2012-10-24 EP EP12775513.0A patent/EP2780025B1/en active Active
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- 2012-10-24 PL PL12775513T patent/PL2780025T3/en unknown
- 2012-10-24 UA UAA201405471A patent/UA110735C2/en unknown
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| AU2012330478A1 (en) | 2014-04-24 |
| RU2014115214A (en) | 2015-12-10 |
| AU2012330478B2 (en) | 2016-12-08 |
| HUE026719T2 (en) | 2016-07-28 |
| CA2851947A1 (en) | 2013-05-02 |
| EP2780025B1 (en) | 2015-12-16 |
| PL2780025T3 (en) | 2016-04-29 |
| MX348397B (en) | 2017-06-08 |
| ES2559293T3 (en) | 2016-02-11 |
| KR20140087018A (en) | 2014-07-08 |
| EP2780025A1 (en) | 2014-09-24 |
| UA110735C2 (en) | 2016-02-10 |
| DE102011085413A1 (en) | 2013-05-02 |
| RU2608442C2 (en) | 2017-01-18 |
| WO2013060714A1 (en) | 2013-05-02 |
| CN104768562A (en) | 2015-07-08 |
| MX2014005008A (en) | 2014-07-09 |
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