WO1999016435A1 - Pharmaceutical compositions containing ricinoleic acid and their use in anti-inflammatory and analgesic therapy - Google Patents
Pharmaceutical compositions containing ricinoleic acid and their use in anti-inflammatory and analgesic therapy Download PDFInfo
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- WO1999016435A1 WO1999016435A1 PCT/EP1998/006070 EP9806070W WO9916435A1 WO 1999016435 A1 WO1999016435 A1 WO 1999016435A1 EP 9806070 W EP9806070 W EP 9806070W WO 9916435 A1 WO9916435 A1 WO 9916435A1
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- ricinoleic acid
- use according
- esters
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- pharmaceutically acceptable
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
Definitions
- the present invention refers to pharmaceutical compositions containing as active principle ricinoleic acid and to their use for the treatment of pain caused by inflammations and allergies.
- state of the art
- Tachykinines (Substance P and neurokinin A) which are locally released by peripheral nerve ending of the primary afferent fibres of type C play an important role in many inflammatory and allergic pathologies. Moreover, this group of sensory nerves carries nociceptive information from the peripheral to the central nervous system. From the pharmacological point of view these nerves are characterised by their specific sensibility to capsaicine and represent the main determinants of pathologies characterised by neurogenic inflammation. Capsaicine has been used for more than twenty years both for studying pain neurophysiolgy and in the therapy of some neuropathies and skin affections.
- capsaicine acts on a sub-group of primary afferent nerves (mainly type C fibres) binding to a receptor of the nervous ending and causing the release of tachykinines. It is also accepted that its pharmacological effect takes place in to phases, first exciting and thereafter desensitising the nerve to the nociceptive stimulation. At the skin level the excitation gives a strong burning and tingling feeling in the derma area where the capsaicine is applied. The desensitising corresponds to a depletion phase of tachykinins and concurrent inhibition of the afferent sensory function of such nervous fibres.
- capsaicine is useful in the treatment of pain neurological disorders and other disorders having inflammatory cause on the other hand its use is strongly limited by its side effects. These side effects are mainly tingling and burning, these sensations can be rather strong, following the topical application on the skin or mucous membranes or injection in tissues like the derma, cerebrospinal canal or blood vessels.
- compositions containing capsaicine in combination with anaesthetics could not reduce satisfactorily the burning sensation. Therefore it is still necessary to find a product capable of desensitising primary afferent nerves without producing the irritant or painful side effects.
- Such product would have interesting application in therapy for many neurological and inflammatory disorders characterised by a nervous inflammatory component or by an exaggerated stimulation of the capsaicine-sensible nervous fibres.
- ricinoleic acid [R-(Z)-12-hydroxy-9-octadecanoic acid or d-12- hydroxyoleic acid (see formula (I)] is the main component of castor oil (it contains about 87% of ricinoleic acid), known for its lassative properties.
- the analgesic properties as the inhibition of neurogenic inflammation of ricinoleic oil, which are at the basis of the present invention were never described before nor could be inferred on the basis of its properties already reported in literature, for example: inhibition of phospholypase A 2 , (WO 91/03512), direct cell damage (Gaginella et al.
- Gastrenterology, 1977, 73, 95-101 inhibition of leukotriene B 4 (Vasange-Tuominen et al. Prostaglandins, Leukotrienes Essent. Fatty Acids, 1994, 50(5), 279-84), alteration of mucosae membrane permeability (Gaginella et al. Gastroenterology, 1977, 73, 95-101 ), stimulation of the adenyl cyclase-cyclic AMP system (Racusen and Binder, I. Clin. Invest., 1979, 63, 743-9) or release of prostaglandins (Beibler and Juan, J. Pharm. Pharmacol., 1979, 63, 681-5).
- the present invention allows to overcome the above said problems thanks to pharmaceutical compositions containing as active principle ricinoleic acid having anti-inflammatory and analgesic properties.
- ricinoleic acid possess the necessary characteristic to overcome the previously described problems.
- Ricinoleic acid is easily available on the market as solution of 80% - 99% purity. It can be used as such or mixed up with the suitable pharmaceutical carriers in order to be administered in composition containing it in a quantity comprised between 0.01 and 100% by weight.
- the present invention comprises also the pharmaceutical composition containing castor oil, as a source of ricinoleic acid, and their use for the above mentioned pathologies.
- the anti-inflammatory/analgesic composition can be administered orally, topically (transdermal or trans-mucosal), intranasal, epidural, intrarectal, parenteral or intravenously to human or animal patients.
- the present invention refers to pharmaceutical composition for use as anti- inflammatory or analgesic containing ricinoleic acid as active principle eventually in combination with the suitable carriers and/or excipient.
- the present invention is useful for the treatment of various kind of painful inflammation disorders as for example: neuralgia, rheumatoid and painful arthritis, bursitis, myositis, eczema, psoriasis, sprains, allergic and vasomotor rhinitis, postherpetic neuralgia, trifacial neuralgia, muscular dilaceration, hematoma, bruise, carpal tunnel syndrome, enteral inflammation , colon irritability syndrome, haemorrhoids, ulcerative rectocolitis, blepharitis, diabetic neuropathy, cluster headache, pain therapy post-mastectomy, acne, conjunctivits, urticaria, itching, orofacial pain, detrusor hyperreflexia, uracratia, asthma and al pathologies characterised by neurogena inflammation and stimulation of the capsaicin- sensible
- Ricinoleic acid as normally used in the present invention has purity comprised between 99%-80%, for example 87%, preferably ricinoleic acid having purity higher than 97% is used.
- castor oil can be used wherein the ricinoleic acid is present in a concentration comprised between 80-90%, preferably 87% and wherein also oleic, linoleic, palmitic and stearic acids are present.
- the treatment with the composition according to the invention can consist in a single application per day or can be repeated during the day.
- the treatment can be repeated for 10-15 days without interruption.
- the compositions according to the present invention do not involve any irritation on the skin or the mucosae, contrary to what happens when capsaicine or its analogues are applied. Moreover they do not present the other side effects which are often associated to the administration of the well known non-steroidal anti- inflammatory agents having similar therapeutic effects, such as: somnolence, confusion, gastric disorders, gastric bleeding, and kidneys disorders.
- the present invention refers obviously also to pharmaceutical composition comprising other products as gelifiers and fillers, flavouring agents and various excipients for oral, topical, parenteral, intravenous, intranasal and intrarectal application as it is known to the men skilled in the art.
- Compositions according to the present invention may include also other products having antibacterial, antifungal, antiprotozoal and antiviral action. Accordingly to the above said, it is an object of the present invention to make available a composition and a method for the treatment of inflammatory and painful disorder by oral, topical (transdermal/transmucosal), intranasal, intrarectal, parenteral or intravenous application.
- Cream for topic use :
- Castor oil (87% in ricinoleic acid) 500 mg in a hard gelatine capsule type 00 or in a soft gelatine capsule.
- Example 5 Castor oil (87% in ricinoleic acid) 500 mg in a hard gelatine capsule type 00 or in a soft gelatine capsule.
- ricinoleic acid as analgesic and antiinflammatory, and the absence of irritation after administration can be illustrated by the following tests.
- Dunkin-Hartley guinea pigs (weight 250-350 g) were treated. Ricinoleic acid at concentration of 30 mM was applied topically on the right eyelid 30 minutes before inducing the oedema by intradermal injection of 300 micrograms of carrageen in 0.1 ml of PBS. Thereafter the animals were treated topically with 30 mM ricinoleic acid once a day for the following 6 days. The control were treated topically with the ricinoleic acid carrier (peanuts oil). The eight day the animals were again treated topically with the carrier or the ricinoleic acid 30 minutes before a new induction of the oedema in the right eyelid by an intradermic injection of carrageen.
- the oedema entity was quantified measuring, by an ophthalmic calibre, the eyelid thickness (mm) before and 3 hours after the carrageen injection. In the same animals the carrageen oedema was repeated after 7 and 21 days after the interruption of the treatment with ricinoleic acid. Table 1 reports the oedema values measured 3 hours after the injection in the last day of the treatment and after 7 and 21 days. The reported values refer to 6 animal per group, at least. Group Days after Eyelid oedema lnhib.% last treatment (mm) (M+SEM)
- Ricinoleic acid after 8 days of treatment, produced a marked and persistent antiinflammatory effect. The effect persisted for at least 3 weeks after the treatment.
- the right eye conjunctiva of guinea pigs is treated topically twice a day with 10 microliters of solutions containing 0.1 , 1 and 10 mg/ml of ricinoleic acid.
- 10 microliters of a solution containing 1 mg/ml of capsaicine is applied to the right eye conjunctiva and the cleansing movements were numbered during the first 5 minutes following the application.
- the data reported in the following Table refers to six animals for each group.
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- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
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Abstract
The application refers to the use of ricinoleic acid, its esters or pharmaceutically acceptable salts in the treatment of pain caused by inflammations or allergies.
Description
PHARMACEUTICAL COMPOSITIONS CONTAINING RICINOLEIC ACID AND
THEIR USE IN ANTI-INFLAMMATORY AND ANALGESIC THERAPY
Field of the invention
The present invention refers to pharmaceutical compositions containing as active principle ricinoleic acid and to their use for the treatment of pain caused by inflammations and allergies. State of the art
Tachykinines (Substance P and neurokinin A) which are locally released by peripheral nerve ending of the primary afferent fibres of type C play an important role in many inflammatory and allergic pathologies. Moreover, this group of sensory nerves carries nociceptive information from the peripheral to the central nervous system. From the pharmacological point of view these nerves are characterised by their specific sensibility to capsaicine and represent the main determinants of pathologies characterised by neurogenic inflammation. Capsaicine has been used for more than twenty years both for studying pain neurophysiolgy and in the therapy of some neuropathies and skin affections. It is accepted that capsaicine acts on a sub-group of primary afferent nerves (mainly type C fibres) binding to a receptor of the nervous ending and causing the release of tachykinines. It is also accepted that its pharmacological effect takes place in to phases, first exciting and thereafter desensitising the nerve to the nociceptive stimulation. At the skin level the excitation gives a strong burning and tingling feeling in the derma area where the capsaicine is applied. The desensitising corresponds to a depletion phase of tachykinins and concurrent inhibition of the afferent sensory function of such nervous fibres. If it is true that capsaicine is useful in the treatment of pain neurological disorders and other disorders having inflammatory cause on the other hand its use is strongly limited by its side effects. These side effects are mainly tingling and burning, these sensations can be rather strong, following the topical application on the skin or mucous membranes or injection in tissues like the derma, cerebrospinal canal or blood vessels.
The efforts aimed to eliminate or reduce the side effects of capsaicine or its analogues gave very poor results. For example, resiniferatoxin, was described as
a very potent analogue having a lower irritating effect, but since this product is an ester of phorbole it could have carcinogenic properties.
Moreover pharmaceutical compositions containing capsaicine in combination with anaesthetics could not reduce satisfactorily the burning sensation. Therefore it is still necessary to find a product capable of desensitising primary afferent nerves without producing the irritant or painful side effects. Such product would have interesting application in therapy for many neurological and inflammatory disorders characterised by a nervous inflammatory component or by an exaggerated stimulation of the capsaicine-sensible nervous fibres. It is also known that ricinoleic acid [R-(Z)-12-hydroxy-9-octadecanoic acid or d-12- hydroxyoleic acid (see formula (I)] is the main component of castor oil (it contains about 87% of ricinoleic acid), known for its lassative properties. The analgesic properties as the inhibition of neurogenic inflammation of ricinoleic oil, which are at the basis of the present invention were never described before nor could be inferred on the basis of its properties already reported in literature, for example: inhibition of phospholypase A2, (WO 91/03512), direct cell damage (Gaginella et al. Gastrenterology, 1977, 73, 95-101 ), inhibition of leukotriene B4 (Vasange-Tuominen et al. Prostaglandins, Leukotrienes Essent. Fatty Acids, 1994, 50(5), 279-84), alteration of mucosae membrane permeability (Gaginella et al. Gastroenterology, 1977, 73, 95-101 ), stimulation of the adenyl cyclase-cyclic AMP system (Racusen and Binder, I. Clin. Invest., 1979, 63, 743-9) or release of prostaglandins (Beibler and Juan, J. Pharm. Pharmacol., 1979, 63, 681-5).
OH ( I )
Detailed description of the invention The present invention allows to overcome the above said problems thanks to pharmaceutical compositions containing as active principle ricinoleic acid having anti-inflammatory and analgesic properties.
In fact, it was surprisingly found that ricinoleic acid possess the necessary characteristic to overcome the previously described problems. Ricinoleic acid is easily available on the market as solution of 80% - 99% purity. It can be used as such or mixed up with the suitable pharmaceutical carriers in order to be administered in composition containing it in a quantity comprised between 0.01 and 100% by weight.
The present invention comprises also the pharmaceutical composition containing castor oil, as a source of ricinoleic acid, and their use for the above mentioned pathologies. The anti-inflammatory/analgesic composition can be administered orally, topically (transdermal or trans-mucosal), intranasal, epidural, intrarectal, parenteral or intravenously to human or animal patients.
The present invention refers to pharmaceutical composition for use as anti- inflammatory or analgesic containing ricinoleic acid as active principle eventually in combination with the suitable carriers and/or excipient.
By administering the composition, for example topically on the inflamed area, it is possible to hale more efficiently the inflammation disorders. The present invention is useful for the treatment of various kind of painful inflammation disorders as for example: neuralgia, rheumatoid and painful arthritis, bursitis, myositis, eczema, psoriasis, sprains, allergic and vasomotor rhinitis, postherpetic neuralgia, trifacial neuralgia, muscular dilaceration, hematoma, bruise, carpal tunnel syndrome, enteral inflammation , colon irritability syndrome, haemorrhoids, ulcerative rectocolitis, blepharitis, diabetic neuropathy, cluster headache, pain therapy post-mastectomy, acne, conjunctivits, urticaria, itching, orofacial pain, detrusor hyperreflexia, uracratia, asthma and al pathologies characterised by neurogena inflammation and stimulation of the capsaicin- sensible sensor nerves.
Ricinoleic acid as normally used in the present invention has purity comprised between 99%-80%, for example 87%, preferably ricinoleic acid having purity higher than 97% is used.
As already said also castor oil can be used wherein the ricinoleic acid is present in a concentration comprised between 80-90%, preferably 87% and wherein also
oleic, linoleic, palmitic and stearic acids are present.
The treatment with the composition according to the invention can consist in a single application per day or can be repeated during the day. The treatment can be repeated for 10-15 days without interruption. The compositions according to the present invention do not involve any irritation on the skin or the mucosae, contrary to what happens when capsaicine or its analogues are applied. Moreover they do not present the other side effects which are often associated to the administration of the well known non-steroidal anti- inflammatory agents having similar therapeutic effects, such as: somnolence, confusion, gastric disorders, gastric bleeding, and kidneys disorders.
The present invention refers obviously also to pharmaceutical composition comprising other products as gelifiers and fillers, flavouring agents and various excipients for oral, topical, parenteral, intravenous, intranasal and intrarectal application as it is known to the men skilled in the art. Compositions according to the present invention may include also other products having antibacterial, antifungal, antiprotozoal and antiviral action. Accordingly to the above said, it is an object of the present invention to make available a composition and a method for the treatment of inflammatory and painful disorder by oral, topical (transdermal/transmucosal), intranasal, intrarectal, parenteral or intravenous application.
It is another object of the present application to make available a composition and a method for the treatment of inflammatory pathologies which is safe and effective without presenting the side effects of capsaicine and its analogues or of the conventional therapy using non steroidal anti-inflammatories. Hereinafter some examples of pharmaceutical compositions according to the invention are reported:
Example 1
Gel for topic application:
Ricinoleic acid 5%
Cellulose ether 4%
Glycerin 30%
Preservative q.s.
Distilled water q.s. to 100
Example 2
Cream for topic use:
Ricinoleic acid 8 g
Stearyl alcohol 7.2 g
Vaseline 25 g
Propylenglycol 12 g
Tween 20 0.5 g
Methyl-p-oxybenzoate 0.025 g
Propyl p-oxybenzoate 0.015 g
Cellulose (microcrystal) 47.26 g
Example 3
Ointment for topic administration:
Ricinoleic acid 5 g
Polyglycol 4000 19 g
Glycerin 30 g
Stearyl alcohol 30 g
Sodium laurylsulfate 1 9
Distilled water 15 g
Example 4
Capsule for oral administration:
Castor oil (87% in ricinoleic acid) 500 mg in a hard gelatine capsule type 00 or in a soft gelatine capsule.
Example 5
Tablet for oral administration
Ricinoleic acid 500 mg
Avicel 400 mg
Colloidal Silica 200 mg
Magnesium stearate 10 mg
Example 6
Emulsion for injections:
Ricinoleic acid 10
Soya phospholipides 1.2
Sorbitole 5 g
Water for injection q.s. to 100 ml.
The pharmacological activity of ricinoleic acid as analgesic and antiinflammatory, and the absence of irritation after administration can be illustrated by the following tests.
Antiinflammatory effect of ricinoleic acid in carrageen-edema induced in guinea pig eyelid.
Dunkin-Hartley guinea pigs (weight 250-350 g) were treated. Ricinoleic acid at concentration of 30 mM was applied topically on the right eyelid 30 minutes before inducing the oedema by intradermal injection of 300 micrograms of carrageen in 0.1 ml of PBS. Thereafter the animals were treated topically with 30 mM ricinoleic acid once a day for the following 6 days. The control were treated topically with the ricinoleic acid carrier (peanuts oil). The eight day the animals were again treated topically with the carrier or the ricinoleic acid 30 minutes before a new induction of the oedema in the right eyelid by an intradermic injection of carrageen. The oedema entity was quantified measuring, by an ophthalmic calibre, the eyelid thickness (mm) before and 3 hours after the carrageen injection. In the same animals the carrageen oedema was repeated after 7 and 21 days after the interruption of the treatment with ricinoleic acid. Table 1 reports the oedema values measured 3 hours after the injection in the last day of the treatment and after 7 and 21 days. The reported values refer to 6 animal per group, at least.
Group Days after Eyelid oedema lnhib.% last treatment (mm) (M+SEM)
Control 0.98 +0.1 —
Ricinoleic acid 0 -0.16 +0.02 100
Ricinoleic acid 7 0.07+_0.02 93
Ricinoleic acid 21 0.10+_0.01 90
Ricinoleic acid, after 8 days of treatment, produced a marked and persistent antiinflammatory effect. The effect persisted for at least 3 weeks after the treatment.
Absence of irritation of ricinoleic acid on the guinea pig conjunctiva. Ricinoleic acid (0.1-10 mg/ml, 10 microliters on the right conjunctiva) was tested for its irritant effect after direct application on the conjunctiva of non anhaestetized guinea pigs. Capsaicine (0.10 - 1 mg/ml) was used as control. The animals were observed and the number of cleansing movements of the eyelid were numbered in the 5 minutes following the application. At least five animals per group were tested.
Group Concentration N° cleansing/min
(mg/ml) (M+SEM)
Ricinoleic acid 0.1 0.03+0.1
1 4.00+0.3
10 3.00+0.4
Capsaicine 0.01 11.00+1
0.1 23.00+4
1 37.00+5
The data show that ricinoleic acid up to the highest concentration used has a minimal irritating effect on the non anaesthetised guinea pigs conjunctiva, being at least 100 fold less irritating than capsaicine
Analgesic effect of ricinoleic acid
The right eye conjunctiva of guinea pigs is treated topically twice a day with 10 microliters of solutions containing 0.1 , 1 and 10 mg/ml of ricinoleic acid. At the eight day 10 microliters of a solution containing 1 mg/ml of capsaicine is applied to the right eye conjunctiva and the cleansing movements were numbered during the first 5 minutes following the application. The data reported in the following Table refers to six animals for each group.
Group Concentration N° cleansing/min lnhib.%
(mg/ml) (M+SEM)
Capsaicine 1 37+5 —
Ricinol. Acid 0.1 26+3 31
1 15+2 59
10 9±2 76
Eight days treatment with ricinoleic acid produced a dose-dependent analgesic effect reducing the effect induced by capsaicine.
Claims
Claims
1. Use of ricinoleic acid, its esters or pharmaceutically acceptable salts, possibly in combination with a pharmaceutically acceptable carrier, for the manufacture of an antiinflammatory and analgesic medicament for pathologies characterised by neurogena inflammation mediated by the stimulation of capsaicine-sensible sensory fibres.
2. Use according to claim 1 wherein the ricinoleic acid, its salts or esters, has a purity higher than 80%.
3. Use according to claim 2 wherein the ricinoleic acid, its salts or esters, has a purity higher than 90%.
4. Use according to claim 1 wherein the ricinoleic acid, its salts or esters, has a purity higher than 97%.
5. Use according to Claim 1 wherein the ricinoleic acid is in the form of castor oil containing ricinoleic acid in a concentration comprised between 80 - 90%, preferably 97%.
6. Use according to Claim 1 wherein the ricinoleic acid, its salts or esters, is present in a concentration of 0.1 - 100% (by weight).
7. Use according to claim 6 wherein the ricinoleic acid, its salts and esters, is present in concentration 0.5 - 10% by weight. 8. Use according to Claim 1 wherein the analgesic and antiinflammatory medicament is for the treatment of painful, inflammatory or allergic pathologies acute or chronic.
9. use according to Claim 8 for the treatment of: neuralgia, rheumatoid and painful arthritis, bursitis, myositis, eczema, psoriasis, sprains, allergic and vasomotor rhinitis, postherpetic neuralgia, trifacial neuralgia, muscular dilaceration, hematoma, bruise, carpal tunnel syndrome, enteral inflammation , colon irritability syndrome, haemorrhoids, ulcerative rectocolitis, blepharitis, diabetic neuropathy, cluster headache, pain therapy post-mastectomy, acne, conjunctivits, urticaria, itching, orofacial pain, detrusor hyperreflexia, uracratia, asthma. 10. Use according to claim 1 wherein the medicament is for topical application on the skin.
ricinoleic acid is used in the form of lotion, solution, cream, gel, transdermic plaster or paste in combination with the suitable excipients. 12. Use according to Claim 1 wherein the medicament is for application on mucosae. 13. Use according to Claim 12 wherein the ricinoleic acid is used in the form of solution, suspension, nasal spray, suppositories.
14. Use according to Claim 1 wherein the medicament is for injections.
15. Use according to Claim 1 wherein the medicament is for intranasal administration. 16. Use according to Claim 1 wherein the medicament is for oral administration.
17. Use according to Claim 1 wherein the ricinoleic acid is used in combination with at least another principle having antibacterial, antifungal, antiprotozoal or antiviral activity.
18. Pharmaceutical composition containing ricinoleic acid, its esters or pharmaceutically acceptable salts, for use as antiinflammatory and analgesic in pathologies characterised by neurogena inflammation mediated by the stimulation of capsaicine-sensible sensory fibres.
19. Composition according to Claim 18 for the treatment acute or chronic treatment of painful inflammatory or allergic pathologies. 20. Composition according to claim 18 wherein the ricinoleic acid, its esters or salts, is present in concentration 0.1 - 30% by weight.
21. Composition according to claim 18 for topical treatment by application on the skin.
22. Composition according to claim 21 in the form of lotion, solution, cream, gel, transdermic plaster or paste.
23. Composition according to Claim 18 for application on mucosae.
24. Composition according to Claim 23 in the form of solution, suspension, nasal spray, suppositories.
25. Compositions according to Claim 18 for injection. 26. Composition according to claim 18 for intranasal application.
27. Composition according to Claim 18 for oral administration.
28. Composition according to claim 18, containing at least another principle having
antibacterial, antifungal, antiprotozoal or antiviral activity.
29. Composition containing ricinoleic acid, its esters or pharmaceutically acceptable salts, possibly in combination with a pharmaceutically acceptable excipient for topical administration. 30. Composition according to claim 29 wherein the topical application is on skin.
31. Composition according to Claim 29 wherein the topical application is on mucosae.
32. Composition according to claim 31 wherein the application is intranasal.
33. Composition containing ricinoleic acid, its ester or pharmaceutically acceptable salts, possibly in combination with a pharmaceutically acceptable carrier, for application by injection.
34. Composition containing ricinoleic acid, its esters or pharmaceutically acceptable salts, possibly in combination with a pharmaceutically acceptable carrier, for application as suppository.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU10263/99A AU1026399A (en) | 1997-09-29 | 1998-09-23 | Pharmaceutical compositions containing ricinoleic acid and their use in anti-inflammatory and analgesic therapy |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITFI97A000217 | 1997-09-29 | ||
| ITFI970217 IT1295658B1 (en) | 1997-09-29 | 1997-09-29 | PHARMACEUTICAL COMPOSITIONS CONTAINING RICINOLEIC ACID AND THEIR USE FOR ANTI-FLAMMATORY AND ANALGESIC THERAPY |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1999016435A1 true WO1999016435A1 (en) | 1999-04-08 |
Family
ID=11352253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1998/006070 Ceased WO1999016435A1 (en) | 1997-09-29 | 1998-09-23 | Pharmaceutical compositions containing ricinoleic acid and their use in anti-inflammatory and analgesic therapy |
Country Status (4)
| Country | Link |
|---|---|
| AR (1) | AR010432A1 (en) |
| AU (1) | AU1026399A (en) |
| IT (1) | IT1295658B1 (en) |
| WO (1) | WO1999016435A1 (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8309053B2 (en) * | 2003-04-17 | 2012-11-13 | The General Hospital Corporation | Method for monitoring blood flow and metabolic uptake in tissue with radiolabeled alkanoic acid |
| WO2014129384A1 (en) * | 2013-02-21 | 2014-08-28 | 国立大学法人京都大学 | Intestinal tract-protecting agent containing hydroxylated fatty acid |
| US20140271946A1 (en) * | 2013-03-15 | 2014-09-18 | Altria Client Services Inc. | Modifying taste and sensory irritation of smokeless tobacco and non-tobacco products |
| WO2015111701A1 (en) * | 2014-01-24 | 2015-07-30 | 国立大学法人京都大学 | Anti-inflammatory agent containing rare fatty acid |
| US20150342916A1 (en) * | 2012-10-29 | 2015-12-03 | Kyoto University | Metabolism-improving agent comprising rare fatty acid |
| US9572844B2 (en) | 2013-02-22 | 2017-02-21 | Nitto Pharmaceutical Industries, Ltd. | Immunostimulation agent |
| US11957152B2 (en) | 2010-04-14 | 2024-04-16 | Altria Client Services Llc | Preformed smokeless tobacco product |
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|---|---|---|---|---|
| BE829678A (en) * | 1974-05-31 | 1975-09-15 | READY-TO-USE LIQUID MEDICINAL PRODUCT EXERCISING ANTI-MICROBIAL EFFECT | |
| DE2423397A1 (en) * | 1974-05-14 | 1975-11-27 | Heimbach Irmgard | Deep-acting collodion solution medicament - contg. Terebinthina, castor oil, plant extracts, and salicylic acid |
| FR2485001A1 (en) * | 1980-06-02 | 1981-12-24 | Svatos Antonin | 4-Chloro and 2,4-di:chloro 3,5-xylyl ricinoleate(s) - used as fungicides, insecticides, parasiticides and antiinflammatories |
| US4919934A (en) * | 1989-03-02 | 1990-04-24 | Richardson-Vicks Inc. | Cosmetic sticks |
| WO1991003512A1 (en) * | 1989-08-29 | 1991-03-21 | Virginia Commonwealth University | Cytoprotective fatty moiety compounds |
| DE19544507A1 (en) * | 1995-11-29 | 1997-06-05 | Sandoz Ag | Cyclosporin containing preparations |
| US5686488A (en) * | 1995-08-25 | 1997-11-11 | Alcon Laboratories, Inc. | Polyethoxylated castor oil products as anti-inflammatory agents |
-
1997
- 1997-09-29 IT ITFI970217 patent/IT1295658B1/en active IP Right Grant
-
1998
- 1998-09-23 AU AU10263/99A patent/AU1026399A/en not_active Abandoned
- 1998-09-23 WO PCT/EP1998/006070 patent/WO1999016435A1/en not_active Ceased
- 1998-09-30 AR ARP980104875 patent/AR010432A1/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| ITFI970217A1 (en) | 1999-03-29 |
| AR010432A1 (en) | 2000-06-07 |
| AU1026399A (en) | 1999-04-23 |
| IT1295658B1 (en) | 1999-05-24 |
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