MXPA99011357A - Composition comprising ketanserin and l-carnitine or an alkanoyl l-carnitine for the treatment of crps - Google Patents
Composition comprising ketanserin and l-carnitine or an alkanoyl l-carnitine for the treatment of crpsInfo
- Publication number
- MXPA99011357A MXPA99011357A MXPA/A/1999/011357A MX9911357A MXPA99011357A MX PA99011357 A MXPA99011357 A MX PA99011357A MX 9911357 A MX9911357 A MX 9911357A MX PA99011357 A MXPA99011357 A MX PA99011357A
- Authority
- MX
- Mexico
- Prior art keywords
- carnitine
- alkanoyl
- acid
- ketanserin
- pharmacologically acceptable
- Prior art date
Links
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 title claims abstract description 42
- -1 alkanoyl l-carnitine Chemical compound 0.000 title claims abstract description 35
- FPCCSQOGAWCVBH-UHFFFAOYSA-N Ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 229960005417 ketanserin Drugs 0.000 title claims abstract description 31
- 239000000203 mixture Substances 0.000 title claims description 33
- 229960001518 levocarnitine Drugs 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000011780 sodium chloride Substances 0.000 claims abstract description 25
- 239000002253 acid Substances 0.000 claims description 25
- 238000001802 infusion Methods 0.000 claims description 11
- 238000001990 intravenous administration Methods 0.000 claims description 10
- 230000001225 therapeutic Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 229940009098 Aspartate Drugs 0.000 claims description 6
- CKLJMWTZIZZHCS-UHFFFAOYSA-N DL-aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 6
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N fumaric acid Chemical compound OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-L maleate(2-) Chemical compound [O-]C(=O)\C=C/C([O-])=O VZCYOOQTPOCHFL-UPHRSURJSA-L 0.000 claims description 6
- 229940095064 tartrate Drugs 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- RDHQFKQIGNGIED-MRVPVSSYSA-N Acetylcarnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 claims description 4
- UFAHZIUFPNSHSL-MRVPVSSYSA-N O-propanoyl-L-carnitine Chemical compound CCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C UFAHZIUFPNSHSL-MRVPVSSYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004432 carbon atoms Chemical group C* 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- NDVRKEKNSBMTAX-BTVCFUMJSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O NDVRKEKNSBMTAX-BTVCFUMJSA-N 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K 2qpq Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- QWYFHHGCZUCMBN-SECBINFHSA-N O-butanoyl-L-carnitine Chemical compound CCCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C QWYFHHGCZUCMBN-SECBINFHSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- IGQBPDJNUXPEMT-SNVBAGLBSA-N isovaleryl-L-carnitine Chemical compound CC(C)CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C IGQBPDJNUXPEMT-SNVBAGLBSA-N 0.000 claims description 3
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 3
- PXQPEWDEAKTCGB-UHFFFAOYSA-M orotate Chemical compound [O-]C(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-M 0.000 claims description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-L oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 239000003708 ampul Substances 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims 3
- JZWGYZLPEYCFFC-GFCCVEGCSA-N C(CCCC)(=O)[C@](O)(C[N+](C)(C)C)CC([O-])=O Chemical compound C(CCCC)(=O)[C@](O)(C[N+](C)(C)C)CC([O-])=O JZWGYZLPEYCFFC-GFCCVEGCSA-N 0.000 claims 2
- DSLZVSRJTYRBFB-DUHBMQHGSA-L galactarate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C([O-])=O DSLZVSRJTYRBFB-DUHBMQHGSA-L 0.000 claims 2
- 208000002193 Pain Diseases 0.000 description 19
- 206010053552 Allodynia Diseases 0.000 description 10
- 210000003491 Skin Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 206010065952 Hyperpathia Diseases 0.000 description 4
- 208000008454 Hyperhidrosis Diseases 0.000 description 3
- 206010061255 Ischaemia Diseases 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 230000001684 chronic Effects 0.000 description 3
- 230000037315 hyperhidrosis Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 210000003414 Extremities Anatomy 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 206010022114 Injury Diseases 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 2
- 210000003462 Veins Anatomy 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 125000001589 carboacyl group Chemical class 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 231100000486 side effect Toxicity 0.000 description 2
- 230000002195 synergetic Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 208000008787 Cardiovascular Disease Diseases 0.000 description 1
- PHIQHXFUZVPYII-UHFFFAOYSA-N Carnitine Chemical compound C[N+](C)(C)CC(O)CC([O-])=O PHIQHXFUZVPYII-UHFFFAOYSA-N 0.000 description 1
- 229960004203 Carnitine Drugs 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- ACGDKVXYNVEAGU-UHFFFAOYSA-N Guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
- 229960003602 Guanethidine Drugs 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 210000003127 Knee Anatomy 0.000 description 1
- 210000001700 Mitochondrial Membranes Anatomy 0.000 description 1
- 102000004020 Oxygenases Human genes 0.000 description 1
- 108090000417 Oxygenases Proteins 0.000 description 1
- 210000002820 Sympathetic Nervous System Anatomy 0.000 description 1
- VSNFQQXVMPSASB-JTQLQIEISA-N Valerylcarnitine Chemical group CCCCC(=O)O[C@@H](CC([O-])=O)C[N+](C)(C)C VSNFQQXVMPSASB-JTQLQIEISA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000003042 antagnostic Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000002744 anti-aggregatory Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 230000000903 blocking Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cells Anatomy 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 230000001435 haemodynamic Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001077 hypotensive Effects 0.000 description 1
- 230000001771 impaired Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000000051 modifying Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 230000002085 persistent Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- 230000001737 promoting Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002889 sympathetic Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000000304 vasodilatating Effects 0.000 description 1
Abstract
The use of ketanserin in combination with L-carnitine, some alkanoyl L-carnitines and the pharmacologically acceptable salts thereof is disclosed for the treatment of CRPS.
Description
Composition that includes ketanserin and L-carnitine or an alkanoyl L-carnitine for the treatment of Chronic Localized Pain Syndrome
Description of the Invention Pharmaceutical composition for the treatment of Localized Chronic Pain Syndrome. The present invention relates to L-carnitine and lower alkanoyl L-carnitines or pharmacologically acceptable salts thereof in combination with ketanserin for the therapeutic treatment of Chronic Localized Pain Syndrome (SDCL). The SDCL is a pain syndrome, which affects several subjects after a trauma, even a slight entity trauma. It is associated to the SDCL disturbances in blood circulation with ischemia and pain, where, ischemia causes pain and pain causes ischemia. Other important symptoms presented by patients affected by LPS are hyperpathia and allodynia. The origin of the SDCL is not yet clear; for several years it has been considered that the sympathetic nervous system is * involved. REF .: 32153
For that reason, the most effective therapy was carried out by blocking the sympathetic innervation with phenol, thermolesion or treating it with guanethidine. The restoration of circulation with ketanserin, a serotonin antagonist, constituted an improvement in the treatment of such a disease. With this drug it is possible to treat most symptoms, but not those caused by hyperpathia and allodynia [A. Moesker et al., In Konservative Therapie Arterieller Durchblutungsstoerungen, Georg Thieme Verlag (Stuttgart, New York), 148-152, 1986; A. Moesker et al., The'pain Clinic vol. 8, no. 1, 31-37 (1995); A. Moesker et al., Ibid. vol 12, 269-302 (1991)]. More recently, following the identification of the oxygen free radical during SDCL, dimethyl sulfoxide has been used (RJA Goris et al., Free Rad. Res. Co m. 1987, 13-18; WW Zuurmond et al., Acta Anaesthesiol. Sean.) Without any therapeutic result for the symptoms caused by hyperpathy and allodynia. Therapeutic treatment with dimethyl sulfoxide proved effective only during acute LDS. Ketanserin is a well-known synthetic drug (The Merck Index llth Ed., Page 834), which has the formula
and is a specific antagonist of the S2 receptor with hypotensive properties, first described in EP Application No. 13,612. Ketanserin has been used for the evaluation of its effect on the central and coronary haemodynamic circulation [J. Cardiovasc Phar achol 1998 Dec; 32 (6): 983-7]; and in the treatment of intermittent claudication (J. De Cree et al., Lancet 2, 775 (1984).] L-carnitine and alkanoyl L-carnitines are well-known compounds US Patent 4,255,449 and US Patent 4,268,524 describe the use of L-carnitine and alkanoyl L-carnitines, respectively, to normalize high abnormalities of low density lipoproteins (LDL) + very low density lipoproteins (VLDL) to high density lipoproteins (HDL), which is an etiological factor In several cardiovascular diseases, through beta oxidation of fatty acids, L-carnitine is able to prevent its accumulation and to provide the energy requirement for the cell (Bremner Y, TIBS 2, 201, 1977) via extra CoA modulation and intra-mitochondrial.
L-carnitine and particularly propionyl L-carnitine or acetyl L-carnitine can act by varying the lipid substrate from which various vasoconstrictors and factors that promote aggregation are derived as a result of the effects of the oxygenase and lipo-oxygenase cycle, reducing their formation and promoting the synthesis of anti-aggregant and vasodilatory factors. Carnitine contains a single center of asymmetry and therefore can exist as two enantiomers, designated D (+) - carnitine and L (-) - carnitine and obviously in the racemate form. Of these, only L (-) -carnitine is found in the living organism, where it functions as a vehicle to transport fatty acids through the mitochondrial membranes. further, L-carnitine may be in the form of an internal salt or in the pharmacologically acceptable salt form. For the sake of simplicity, reference will now be made only to L-carnitine or alkanoyl L-carnitine, it being understood that the compositions described herein apply to the internal salts of L-carnitine or alkanoyl L-carinitins, or acceptable pharmacological salts of the same . To date, the combined use of L-carnitine and ketanserin is not known for any therapeutic indication.
It has now unexpectedly been found that the coordinated use, term to be explained in detail in successive lines, of L-carnitine or of an alkanoyl L-carnitine in which the straight or branched alkanoyl chain has 2 to 6 carbon atoms, or one of its pharmacologically acceptable salts, in combination with ketanserin shows a potent synergistic effect in the treatment of LDSS. With the composition of the invention, patients are able either to recover from the symptoms of blood circulation or from the symptoms of hyperpathia and allodynia. This pharmacological activity is very important because for the first time it is possible to cure these symptoms in patients affected by the SDCL. The very poor knowledge of toxicity and side effects of L-carnitine or alkanoyl L-carnitine and ketanserin facilitates its coordinated use, according to the invention, particularly useful and safe for the treatment of LDS. In the context of the invention described herein, what is indicated as "coordinated use" of the aforementioned compounds is, either their co-administration, i.e. the substantially simultaneous administration of L-carnitine or one of the alkanoyl L-carnitines, or one of its
pharmacologically acceptable salts, and ketanserin or indifferently, the administration of a composition containing a combination or mixture of the aforementioned active ingredients, in addition to any excipient included. The scope of the present invention therefore comprises both the co-administration of L-carnitine or the alkanoyl L-carnitine, or one of its pharmacologically acceptable salts, together with ketanserin and pharmaceutical compositions, which can be administered orally. , parenterally or by intravenous infusion, containing a mixture of the two active ingredients. In a preferred embodiment of the invention, the alkanoyl L-carnitine will be selected from the group consisting of acetyl, propionyl, butyryl, valeryl and isovaleryl L-carnitine or one of its pharmacologically acceptable salts. What is indicated by pharmacologically acceptable salt of L-carnitine or of an alkanoyl L-carnitine is any salt with an acid that does not give rise to undesirable toxicity or side effects. These acids are well known to pharmacologists and pharmacy experts.
Examples of pharmacologically acceptable salts of L-carnitine or alkanoyl L-carnitine, but not exclusively these, are chloride, bromide, orotate, aspartate, aspartate acid, acid citrate, acid phosphate, fumarate and fumarate acid, lactate, maleate and acid maleate , mucato, acid oxalate, acid sulfate, glucose phosphate, tartrate and acid tartrate. A preferred composition, in unit dosage form, is a composition containing 5-100 mg of ketanserin and 500-3000 mg of L-carnitine or an equivalent amount of alkanoyl L-carnitine. This pharmaceutical composition is useful for the treatment of symptoms related to LDSS. The pharmacological results of experimental studies showing evidence of the surprising and unexpected synergistic effect achieved with the combination of the invention are shown below. In the following description, reference will be made only to L-carnitine, having considered that the compositions described also apply to the aforementioned alkanoyl L-carnitines and pharmacologically acceptable salts of both L-carnitines and the aforementioned alkanoyl L-carnitines .
Diagnostic method of the SDCL The diagnosis of chronic localized pain syndrome was made in the presence of at least five of the following symptoms: persistent pain at rest, increased pain during exercise, abnormal feeling of pain such as hyperpathia or allodynia, cooling of the skin, battered or bruised skin, hyperhidrosis, edema, impairment of mobility. These symptoms were considered at the beginning of the treatment and after three months of oral treatment. All patients gave their informed consent. The patient data are shown in Table 1. .
+,. *
All patients had a surgical history in the affected area of the hand, foot or knee. Although this group comprises only 12 5 patients, they all present the general scheme of patients with LPS found in large studies such as H. JM Veld an et al., The Lancet, 342, 1012-1016 (1993). In a group of 829 patients with SDCL, Veldman had 76% women and 24% men. In the group treated according to the present invention were 67% female and 33% male.
The average age of the Valdeman study was 42 years, in the present study according to the example of the present invention, it was 40.7 years. Veldman found 59% of the SCDL in the upper limit and 41% in the lower limit. In the group were 42% of SDCL in the upper limit and 58% of SDCL in the lower limit. The delay time between the onset of symptoms and the start of treatment was 33 months in the present case. This extremely long interval time is the consequence of two patients with a delay of 108 and 192 months. If we eliminate these two patients, the delay time is reduced to 9.5 months, and for six patients the delay time is six months or less. The objective of the measurement of skin temperature was used to observe the phenomenon of a heating or cooling of the SDCL. ,. * Taking into account that the normal temperature of the skin is 32 ° C, 7 were observed in the cold limit and five normal or in the hot limit. Special attention was given to the symptoms of feeling of abnormal pain, hyperpathy and allodynia. This type of symptoms occurred in six patients.
Treatment All treatments i.v. were carried out after at least 15 minutes of acclimatization at constant temperature (20-23 ° C). - The temperature of the affected limb was recorded with Hewlett Packard electro-skin probe between the digit 4 and 5. Complementing it with records of continuous photoplethysmography of the hand (digit 2) or foot (digit 1) affected, blood pressure and heart rate. All patients received a 10 mg bolus of ketanserin i.v. in a saline infusion run. • The administration of ketanserin was continued at a rate of 4 mg per hour. After one hour, a bolus injection of 1000 mg of L-carnitine was given. After starting the infusion, an oral maintenance therapy was started with ketanserin three times daily 20 mg and L-carnitine three times daily 990 mg.
Results An evaluation was made with seven symptoms to compare the clinical manifestation of the SDCL before and after the infusion treatment, followed by three months of oral therapy.
The seven symptoms were: pain at rest, pain during exercise, impaired mobility, hyperhidrosis, edema, small veins and allodynia / hyperpathy.
A scale with five degrees was used. The nurse recorded the patient's degree of symptoms according to the following scale: absent, mild, reasonable, moderate and severe. Fig. 1 shows the inventory at the start time; Special attention was given to the symptom of allodynia, which is signaled in the first line. This symptom occurred in six of twelve patients. The results after three months are shown in Fig. 2. After intravenous treatment with ketanserin all patients had peripheral circulation of the normalized affected limb, as was demonstrated in the past by Moesker (cited above) and M. H. Harina et al. [Pain, 38,
145-150 (1989)]. The symptom of the small vein disappeared and the temperature of the skin normalized. After three months of treatment with the two compounds according to the invention, patient "F" was a severe case with delay time of 108 months, had
still the worst symptomatology, with pain at rest, pain during exercise and impairment of mobility. Patient "C" was an extraordinary case, who had a good recovery, but still edema and hyperhidrosis. Patient "B" was fully cured of any malignancy of the SDCL, despite the fact that he had three months of an old total blow of the SDCL, with a skin temperature of 29.1 ° C and severely weakened allodynia of the affected foot. It is worth noting that the symptom of allodynia disappeared in all the patients who showed this symptom. Impairment of mobility and pain during exercise did not completely disappear, probably because the treatment time with the combination according to the present invention was very short. Other positive results were obtained by changing the therapeutic treatment protocol mentioned above. In fact, it is possible to increase or decrease the amount of the two compounds, either during the initial intravenous infusion or during the therapeutic maintenance treatment (os). In mild or recent SDCL it is possible to start directly with the therapeutic maintenance treatment (os) mentioned above with ketanserin and L-carnitine, three times daily.
An objective of the present invention is an orally or parenterally administrable composition containing ketanserin and L-carnitine or an alkanoyl L-carnitine or a pharmacologically acceptable salt thereof. The object of the present invention is also the coordinated use of the aforementioned compounds, i.e. the simultaneous administration substantially of the L-carnitine or one of the alkanoyl L-carnitines, or one of its pharmacologically acceptable salts and ketanserin or indifferently, the administration of a composition containing a combination or mixture of the aforementioned active ingredients, in addition to any excipient included. The composition of the invention can be administered orally, parenterally or intravenously by infusion. The composition according to the invention can be in the form of tablets, capsules, effervescent "sachets", suppositories or ampoules. Another point to consider of the present invention is to provide a therapeutic kit that contains in the same package: a) a first set of ampules for intravenous infusion, the first set of ampoules contains 5-50 mg of ketanserin in mixture with vehicle and / or pharmacologically acceptable excipient, a second set of
vials for intravenous infusion, the second set of ampoules contains 500-2000 mg of L-carnitine or an equivalent amount of an alkanoyl L-carnitine or one of the pharmacologically acceptable salts with pharmaceutical composition containing 100-3000 mg thereof, in mixture with pharmacologically acceptable carrier and / or excipient; and also contained in the same package. b) a first orally administrable pharmaceutical composition containing 5-100 mg of ketanserin and a second orally administrable mg of L-carnitine or of an alkanoyl L-carnitine or one of the pharmacologically acceptable salts thereof, in mixture with vehicle and / or pharmacologically acceptable excipient.
It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers.
Claims (4)
1. A combination, characterized in that it consists of ketanserin and L-carnitine or an alkanoyl L-carnitine or one of the pharmacologically acceptable salts thereof.
2. Pharmaceutical composition, characterized in that it contains as active ingredients ketanserin and L-carnitine or an alkanoyl L-carnitine where the straight or branched chain of the alkanoyl group has 2 to 6 carbon atoms or one of the pharmacologically acceptable salts thereof, in mixture with pharmacologically acceptable carrier and / or excipient.
3. The composition according to claim 2, for oral, parenteral or intravenous infusion. The composition according to claim 2, characterized in that the alkanoyl L-carnitine is selected from the group consisting of acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine and isovaleryl L-carnitine. The composition according to claim 2, characterized in that the pharmacologically acceptable salt of L-carnitine or of the alkanoyl L-carnitine is selected from the group consisting of chloride, bromide, orotate, aspartate, aspartate, acid citrate, acid phosphate, fumarate and acid fumarate, lactate, maleate and acid maleate, mucate, acid oxalate, acid sulfate, glucose phosphate, tartrate and acid tartrate. The composition according to claim 2, in unit dosage form, characterized in that it contains 5-100 mg of ketanserin and 100-3000 mg of L-carnitine or of the alkanoyl L-carnitine. The composition according to claim 6, characterized in that it is suitable for oral administration. The composition according to any of the preceding claims for the therapeutic treatment of the SDCL. Coordinated use of ketanserin and L-carnitine or of an alkanoyl L-carnitine or one of its pharmacologically acceptable salts for the treatment of LDS. . A case, characterized in that it comprises in the same package a first series of ampules for intravenous infusion, the first series of ampoules comprises 5- 50 mg of ketanserin in admixture with vehicle and / or pharmacologically acceptable excipient, a second series of vials for intravenous infusion, the second series of vials comprises 500-2000 mg of L-carnitine or an equivalent amount of an alkanoyl L-carnitine where the straight or branched chain of the alkanoyl group has 2 to 6 carbon atoms or pharmacologically acceptable salts thereof, in admixture with pharmacologically acceptable carrier and / or excipient. 11. A package according to claim 10, characterized in that it also contains in the same package a composition of claim 7. 12. A package according to claim 10, characterized in that it also comprises in the same package a first pharmaceutical composition orally administrable containing 5-100 mg of ketanserin and a second orally administrable pharmaceutical composition containing 100-3000 mg of L-carnitine or of an alkanoyl L-carnitine. 13. Use of ketanserin and L-carnitine or of an alkanoyl L-carnitine, characterized by the straight or branched chain of the alkanoyl group having 2 to 6 carbon atoms or one of its pharmacologically acceptable salts for the preparation of a medicament for the treatment of the SDCL. . Use according to claim 13, characterized in that the alkanoyl L-carnitine is selected from the group consisting of acetyl L-carnitine, propionyl L-carnitine, butyryl L-carnitine, valeryl L-carnitine and isovaleryl L-carnitine. . Use according to claim 13, characterized in that the pharmacologically acceptable salt of L-carnitine or of the alkanoyl L-carnitine is selected from the group consisting of chloride, bromide, orotate, aspartate, acid aspartate, acid citrate, acid phosphate, fumarate and fumarate acid, lactate, maleate and acid maleate, mucate, acid oxalate, acid sulfate, glucose phosphate, tartrate and acid tartrate. . Use according to claim 13, characterized in that the medicament comprises 5-100 mg of ketanserin and 100-3000 mg of L-carnitine or of an alkanoyl L-carnitine, in the form of a single unit dosage. . Use according to claim 13, characterized in that the medicament comprises 5-100 mg of ketanserin in a first unit dosage form and 100-3000 mg of L-carnitine or of an alkanoyl L-carnitine in a second unit dosage form, first and second forms of unit doses physically separated from each other.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MIMI98A000774 | 1998-04-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA99011357A true MXPA99011357A (en) | 2000-12-06 |
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