GB2192541A - Bromocriptine - Google Patents
Bromocriptine Download PDFInfo
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- GB2192541A GB2192541A GB08716323A GB8716323A GB2192541A GB 2192541 A GB2192541 A GB 2192541A GB 08716323 A GB08716323 A GB 08716323A GB 8716323 A GB8716323 A GB 8716323A GB 2192541 A GB2192541 A GB 2192541A
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- bromocriptine
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- diabetes
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- glomerulonephritis
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/48—Ergoline derivatives, e.g. lysergic acid, ergotamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
GB2192541A 1 SPECIFICATION quent to preliminary cyclosporin monotherapy or
cyclosporin/Bromocriptine mixed therapy, New use of Bromocriptine e.g. for use in the remission phase of the disease or as maintainance therapy, thus alle The present invention relates to novel means 70 viating the need for continued long term cy of therapy, in particular immunosuppressive closporin therapy.
therapy, for the treatment of auto-immune dis- In accordance with the foregoing the pre ease. More especially the present invention re- sent invention provides a method of treating a lates to novel means of therapy as aforesaid disease selected from the group consisting of:
and comprising administration of Bromocriptine 75 (a)Myasthenia gravis; for the treatment of specific auto-immune dis- (b) Endocrine opthalmopathy; I eases. (c) Graves disease; Bromocriptine, also known as 2-bromo-12'- (d) Juvenile diabetes (diabetes mellitus type hydroxy-2'-(methylethyl)-5'-(2-methylpropyl)-er- 1); gotaman-3',6',18-trione and 2-bromo-a-ergok- 80 (e) Glomerulonephritis (with or without ne ryptin (c.f. MERCK INDEX, 10th. Edition phrotic syndrome); (1983), item 1386) is a known compound (f) Systemic lupus erythematosus; having valuable pharmaceutical properties, in (g) Autoimmune hernatological disorder; particular prolactin secretion inhibitory activity. (h) Multiple sclerosis; and It is commercially available in pharmaceutically 85 (i) Autoimmune inflammatory bowel dis acceptable acid addition salt form, i.e. as the ease; methane sulfonate, under Registered Trade in a subject in need of such treatment, Marks PARLODEL@ and PRAVIDELO, for use which method comprises administering to said in the treatment of e.g. hyperprolactinaernia, subject an effective amount of Bromocriptine.
Parkinson's disease and acromegaly. 90 Specific disease sub-groups to which the In accordance with the present invention it method of the invention is applicable include:
has now surprisingly been found that, of the (el) Idiopathic nephrotic syndrome or mini many various auto-immune diseases known mal change nephropathy; from the literature, effective and advantageous (gl) Heamolytic anaemia; treatment of the specific diseases: 95 (g2) Aplastic anaemia; (a) Myasthenia gravis; (g3) Pure red cell anaemia; (b) Endocrine opthalmopathy; (g4) Idiopathic trhombocytopaenia; (c) Graves disease; (il) Chron's disease; and (d) Juvenile diabetes (diabetes mellitus type (i2) Ulcerative colitis.
3 5 1); 100 As previously indicated Bromocriptine exists (e) Glomerulonephritis (with or without ne- in both free and acid addition salt forms. In phrotic syndrome); general the pharmaceutically acceptable acid (f) Systemic lupus erythematosus; addition salts of Bromocriptine, e.g. the com (g) Autoimmune hernatological disorder; mercially available Bromocriptine mesylate, (h) Multiple Sclerosis; and 105 have been found to have the same level or (i) Autoimmune inflammatory bowel dis- order of tolerability and effectiveriess as the ease; free compound. References to Bromocriptine can be effected employing Bromocriptine as throughout the present specification and monotherapy. For these specific diseases Broclaims are accordingly to be understood as mocriptine alone, administered at appropriate 110 including both the free compound and its dosage rates/in accordance with an appropri- pharmaceutically acceptable acid addition salts ate dosage regimen or technique, provides unless otherwise specified.
adequate and unexpectedly beneficial medica- For use in accordance with the present in tion. vention Bromocriptine is preferably employed This finding may be seen to be of excep- 115 in pharmaceutically acceptable acid addition tional benefit in relation to the long-term treat- salt form, most preferably as Bromocriptine ment of subjects exhibiting the particular dis- mesylate.
eases (a) to (i) listed above, or in the treat- The method in accordance with the present ment of said diseases in subjecis "resistant" invention is especially applicable to subjects to cyclosporin therapy or considered "at risk" 120 undergoing maintainance therapy or in the re- to potential cyclosporin induced organ dam- mission phase of specified diseases (a) to (i).
age, e.g. for the treatment of said diseases in Effectiveness of Bromocriptine in accordance infants and children or in patients already exhi- with the method of the invention may be de biting organ, e.g. kidney or liver, damage or monstrated in standard animal test models as malfunction. 125 well as in clinical trials, carried out e.g. as Thus for the specific listed auto-immune dis- follows:
eases (a) to (i), use of Bromocri.ptine monoth- [For all of the following tests and clinical erapy may be anticipated to be of particular trials, Bromocriptine is administered in the benefit in subjects, e.g. in the "resistant" or form of its mesylate (methane sulfonate) salt].
"at risk" categories above indicated, subse- 130 2 GB2192541A 2 1. JUVENILE DIABETES TYPE/ by intradermal injection into each hind foot 881Worcester Rat Model pad of 0. 1 mi of an emulsion comprising 2.5 The trial is based on the general methodo- 9 bovine spinal cord (lyophylised and reconsti logy described by Like et al. in Am. J. Pathol. tuted with 12 mi H20), 1. 5 m] Arlacel A, 8.0 117, 92-97 (1984). For purposes of the test, 70 mi Nujol and 0.2 m] saline containing 20 mg groups of BB/W (9 and 8) rats (a strain spon- killed, dried Mycobacterium phlei.
taneously developing auto-immune diabetes Test therapy consists of Bromocriptine ad comparable with juvenile diabetes type 1) aged ministered alone at dosages of from 1 to 10 days are employed. mg/kg/day s.c. administered daily or every Test therapy consists of Bromocriptine ad2nd day and continuing ca. 14 days.
ministered alone at dosages of from 3 to 10 During the treatment period, test animals are mg/kg/day administered continously through- examined daily for the symptoms of the dis out the day i.m., for 10 days. ease (paralysis in the hind limbs and tail) and Control groups receive olive oil placebo in disease appearance is scored as positive place of test substance. All test animals are 80 when complete involvement of both hind legs screened regularly for the occurrence of glyco- and the tail is observed. The test animals are suria. kept under observation for a total period of In groups receiving Bromocriptine, substan- 25 days.
tial reduction in the number of animals exhibit- In groups receiving the above therapy, sub ing diabetes, e.g. exhibiting abnormally elestantial reduction in appearance of EAE dis vated blood glucose leveis/glycosuria, is ob- ease symptoms is observed in comparison served in comparison with results for control with results for control groups receiving pla groups receiving placebo. cebo.
2. MYASTHENIA GRAVIS 90 4. SYSTEMIC LUPUS ERYTHEMA TOSUS Experimental Allergic Myasthenia Gravis (NZBI)NZW)Fl mouse model (EAMG) Trials are based on the (NZ13/NZW)F1 Testing is carried out in accordance with the mouse strain as described and discussed by general methodology described by V.A. Len- Steinberg et al. in Bulletin on the Rheumatic non et al. in J. Exp. Med. 141, 1365-1375 95 Diseases 28, Nos. 4-5, 940- 946 (1975). EAMG is induced in groups of 8 to (1977-1978) published by The Arthritis Foun 12 Lewis rats (9) weighing ca. 150200 9 by dation, Atlanta, Georgia. Females of this strain intracutaneous injection of a mixture containing spontaneously develop characteristica of the 1 part Freund's complete adjuvant (Difco, SLE syndrome including formation of anti-DNA 0638-60) and 1 part of a solution comprising 100 and anti-erythrocyte autoantibodies as well as 10, pg purified acetylcholine receptor (obtained proteinurea at age ca. 5 to 7.5 months. The from Torpedo california rats). Additional adju- condition ultimately leads to death.
vant (pertussia, 1 x 1010 units) is administered For the purpose of the trial, groups of 6 to s.c. into the hind paw pad. Autoantibody 8 9 mice are employed.
titres are determined at weekly intervals using 105 Test therapy consists of Bromocriptine ad ELISA technique. ministered at dosages of from 1 to 10 Test therapy consilsts of Bromocriptine ad- mg/kg/day s.c., 5xweekly.
ministered alone at dosages of from 1 to 10 Therapy is applied either prior to spontane mg/kg/day s.c., 5 days a week. ous development of auto-antibodies (e.g. at Therapy commences either: on the day of 110 ca. 5 months age) for determination of pro immunisation, to determine prophylactic effec- phylactic effectiveness, or subsequent to 1 4 tiveness; or after autoantibodies have already spontaneous development of auto-antibodies, been formed (generally ca. 14 days after im- (e.g. at ca. 8-9 months age) for determination munisation) to determine therapeutic effective- of therapeutic effectiveness. In both instances ness. 115 therapy is continued for a total of ca. 8 to 10 In groups receiving the above therapy, sub- weeks. Anti-DNA and anti- erythrocyte anti stantial inhibition of antibody formation em- body titres are measured at regular intervals ploying a prophylactic regime/reduction in during the trial period employing ELISA tech auto-antibody titres employing atherapeutic nique commencing from ca. 1 week prior to regime is observed in comparison with results 120 the start of therapy. Additional parameters for control groups receiving placebo. subject to control are development of protein uria (measured 1 x/week) and life span.
3. MULTIPLE SCLEROSIS In groups receiving the above therapy, sub Activity in Established Experimental Allergic stantial reduction of proteinuria as well as in- Encephalomyelitis (EAQ 125 crease in average life span is observed in both Testing is carried out in accordance with the prophylactic and therapeutic treatments com- general methodology described by Borel et al. pared with results for control groups receiving in -Agents and Action, 6, 468 (1976). EAE is placebo.
induced in groups of 8 to 12 Wistar (9) or Lewis (R) rats each weighing 150 to 200 g, 130 5.AUT0IMMUNE HEMA TOLOGICAL DIS- 3 GB2192541A 3 ORDER (HEMOLYTIC ANAEMIA) computer is used to quantify the intensity of Rat Erythrocyte Induced Anti-Mouse Erythro- the stained urine spots compared to a serial cyte Autoantibody Model dilution of bovine serum albumin. Levels of Testing is carried out in accordance with the protein above 100 mg % are considered ab- general methodology described by Naysmith et 70 normal and positive.
al. Immunological Rev. 55, 54-86 (1981). Mice are sacrificed at the end of each ex Four injections each comprising ca. 1011 well- periment and the kidneys routinely prepared washed rat erythrocytes are administered to for histological examination. Direct immunoflu groups of young, normal/healthy mice at days orescent studies are performed using antisera 0, 7, 14 and 21 of the test, injection being 75 directed against mouse Ig and C3 (Nordic).
effected i.p. From day 21 on the animals are Glomerulonephritis is classified into (i) mild en bled at fixed 5 to 7 day intervals into citrate dothdlialmesangial lesions, (ii) more severe saline, and a direct Coomb's test is performed segmental proliferative, and (iii) most severe using a broad spectrum sheep anti-mouse im- membrano-proliferative type. Scoring is from munoglobulin antiserum. Positive reaction in 80 no lesion progressing to severe lesion. Immu the Coomb's test is generally observed in con- nofluorescent scoring ranges from nothing to trol animals receiving no medication from ca. strong. Results are compared with a control week 3 to 4 of the trial on. The trial is con- group receiving placebo only. If an animal dies tinued for ca. 10 to 12 weeks. while having proteinurea during the experi- Test therapy consists of Bromocriptine alone 85 ment, it is considered positive.
administered at dosages of from 1 to 10 In groups receiving the above therapy, sub mg/kg/day p.o. or s.c., 5 x weekly. stantial reduction of deposition of immuno Therapy is applied either commencing on reactants and histological evidence of glomeru day 0 of the trial for determination of prophy- lonephritis is observed in comparison with re lactic effectiveness or commencing after auto- 90 sults for control groups receiving placebo.
antibodies have been developed (positive reac- Effectiveness of Bromocriptine in accordance tion in Coomb's test, generally ca. 21 to 28 with the method of the invention may also be days after day 0) for determination of thera- shown in clinical trials, e. g. performed as fol peutic effectiveness. In both instances therapy lows:
is continued for a total of ca. 4 to 6 weeks. 95 In groups receiving the above therapy, sub- CLINICAL TRIAL: JUVENILE DIABETES TYPE I stantial reduction in the number of animals re- The trial is carried out employing volunteer, acting positively in the Coomb's test following insulin-dependent diabetics, diagnosed as exhi prophylactic treatment/substantial reduction of biting Juvenile Diabetes Type 1. Diagnosis is response in the Coomb's test following thera- 100 made on clinical grounds in non-obese sub- peutic treatment is observed in comparison - jects with confirmed hyperlycaernia [National with results for control groups receiving pla- Diabetes Data Group, Diabetes 28, 1039 cebo. (1979)].
Baseline creatinine clearance, urinalysis, 6. GLOMERULONEPHRITISINEPHROTIC 105 serum creatinine, blood urea nitrogen, serum SYNDROME glutarnic-oxaloacetic transaminase (SGOT), and Back-Ground alkaline phosphatase levels are determined to Female NZB/W hybrid mice spontaneously ensure that these are normal.
develop renal disease characterised by immu- Trial medication is administered to each noglobulin (1g) and complement (C') deposition 110 subject in accordance with the medication re- at 3 to 6 months of age, with histological gimen below.
glomerulonephritis and proteinurea from about After discharge patients are seen weekly for 6 months, They thus provide an appropriate 2 weeks and monthly thereafter. At each in animal model for the disease glomerulonephri- clinic visit, blood is drawn for determination of tis as it occurs in man. 115 test substance levels, creatinine and electro lyte concentrations and for hernatological and Method liver function tests; basal and glucagon-stimu Female NZB/W mice are randomly sorted lated plasma C-peptide concentrations are into control and treatment groups of 10 mice measured at 1 month and at 3 months inter each. Each mouse is ear-marked to permit in- 120 vals thereafter.
dividual identification. Experiments are started During the course of the trial all patients are when the mice are aged 12, 24 or 36 weeks treated with insulin and are encouraged to ef old and test therapy continues for 12 weeks. fect administration 2xdaily and to monitor Test therapy consists of Bromocriptine ad- blood glucose concentrations using visual ministered -alone at dosages of from 1 to 10 125 matching or reference meter methods with re mg/kg/day p.o., 5 x weekly. agent strips. They are instructed in a diabetic The degree of proteinurea is estimated by diet appropriate for maintainance of normal staining 10 ul urine spots on filter paper with body weight and activity. Insulin dosage is ad bromophenol blue. A thin-layer-chromato- justed as far as possible to achieve a mean graphy scanner connected to an intergrating 130 blood glucose level of 7. 8 m mole/litre before 4 GB2192541A 4 the main meals and evening snack. Insulin do- Bromocriptine will preferably be administered sage is reduced when control of glycaemia is at dosage levels, and/or in accordance with a consistant with these targets or in order to daily administration regimen, and/or in a form avoid hypoglycaernia. Subjects for which insu- permitting round-the-clock, i.e. continuous, re lin is completely withdrawn for at least 1 70 duction of regular serum prolactin levels. In week without loss of target control or devel- normal subj6cts, serum prolactin levels e.g. as opment or ketonuria and who need not. re- determined by radioimmunoassay (RIA), exhibit sume insulin treatment during the course of cyclical variation during any 24 hour period, the study are classed as no longer-insulin-re- with average levels of the order of from ca.
quiring (NIR) and are deemed to be "in remis- 75 3-5 ng/ml (RIA) during the day time rising to sion". Where subjects becoming NIR subse- ca. 15-20 ng/ml (RIA) towards the evening quently develop hyperglycaernia exceeding and at night. Preferably in practicing the treatment goals, application of insulin or-the method of the present invention, bromocrip oral hypoglycemic agent glybenclamide is un- tine dosaging will be effected in such a man dertaken. 80 ner as to ensure that serum prolactin levels do not rise above 5, preferably about 3, more TRIAL MEDICATION REGIMEN preferably about 2 ng/ml (RIA) at any time Bromocriptine alone administered: during any 24 period. Suitably administration (i) initially at a dose of ca. 1.25 mg p.o. at will be effected in such a manner as to ensure sleep for ca. 3-4 days; increasing to- 85 that average serum prolactin levels in any 24 (ii) 1.25 mg/day p.o. in the morning plus hour period do not exceed above 3, preferably 1.25 mg p.o. at sleep for ca. 3-4 days (= 2.5 above 2 or even above 1 ng/ml (RIA).
mg/day in toto); increasing to- In order to achieve continuous reduction of (iii) 1.25 mg p.o., in the morning and 2.5 regular serum prolactin levels as described mg p.o. at sleep for ca. 3-4 days (=3.75 90 above, administration may be effected either mg/day in toto); with- enterally (e.g. orally) or parenterally (e.g. i.m. ) (iv) further possible increment in daily do- in divided doses administered e.g. 2xor sage of ca. 1.25-2.5 mg/day each 3-4 days more, preferably 3 X or more, /day, or by use to a maximum daily dosage of 10 mg/day in of an appropriate sustained release form.
toto. 95 A suitable oral Bromocriptine daily dosage will generally be of the order of from ca. 2.5 RESULTS (preferably ca. 3.75) to ca. 15 mg (preferably Results indicate a marked and significant in- ca. 10 mg) administered in divided doses, e.g.
crease of NIR remission in subjects receiving 2 to 4x/day, preferably 2x/day, for example the above medication as compared with re- 100 with a 1/3 dose at morning and a 2/3 dose mission (i, e. spontaneous NIR remissions) re- in the evening.
corded for groups of juvenile diabetics for Bromocriptine therapy is suitably introduced whom no therapy is attempted or in compari- in a step-wise fashion with incremental in son with NIR remissions recorded in groups of crease in daily dosage rate over a period of juvenile diabetics receiving alternative interven- 105 e.g. 3 to 5 or more weeks, until the final tion therapy. Results indicate effectiveness of desired dosage rate is achieved, for example Bromocriptine monotherapy in accordance with as hereinbefore described in relation to the the present invention. clinical trial method.
Results further indicate that medication is Both oral and parenteral dosage forms for well tolerated, e.g. as evidenced by measureBromocriptine suitable for use in practising the ment of other physiological parameters during method of the invention, are known in the art the course of the trial. and are commercially available. Thus Bromo Equivalent results to the above may be ob- criptine mesylate is commercially available un tained in analogously designed, clinical trials der the Registered Trade Marks Parlodel@ and for subjects exhibiting glomerulonephritis (with 115 Pravidel@ in 2.5 mg tablet form (divisible e.g.
or without nephrotic syndrome), myasthenia to provide a 1.25 mg dosage) as well as in 5 gravis, autoimmune hernatological disorder (in- mg and 10 mg capsule form.
cluding aplastic anaernia, pure red cell The present invention also provides the use anaernia, idiopatic thrombocytopaenia and, in of Bromocriptine for treating a disease se- particular, hemolyticanaemia), systemic lupus 120 lected from the group of diseases (a) to (i) erythematosus, autoimmune inflammato ry dis- mentioned above, as well as the use of Bro ease (including ulcerative colitis and, in particumocriptine for the manufacture of a pharma lar, Chron's disease), endocrine opthalmopa- ceutical composition for treating a disease se thy, Grave's disease or multiple sclerosis, em- lected from the above mentioned group.
ploying Bromocriptine mono-therapy. 125 The present invention further provides a Doses of Bromocriptine, e.g. in the form of pharmaceutical composition which incorporates its mesylate, to be administered in accordance Bromocriptine as active agent, for use in the with the present invention will of course vary, treatment of a disease selected from the e.g. depending on the mode of administration above mentioned group.
and the particular condition to be treated. 130 GB 2 192 541 A 5
Claims (5)
1); Printed by Burgess & Son (Abingdon) Ltd. Con. 1/87.
(e) Glomerulonephritis (with or without ne- phrotic pyndrome); (f) Systemic lupus erythematosus; (9) Autoimmune hematological disorder; (h) Multiple sclerosis; and (i) Autoirrimune inflammatory bowel disease in a subject in need of such treatment, which method comprises administering to said subject an effective amount of Bromocriptine.
2. The use of Bromocriptine for treating a disease selected from the group consisting of:
(a) Myasthenia gravis; (b) Endocrine opthalmopathy; (c) Grave's disease; (d) Juvenile diabetes (diabetes mellitus type 1); (e) Glomerulonephritis (with or without nephrotic syndrome); (f) Systemic lupus erythematosus; (g) Autoimmune hematological disorder; (h) Multiple sclerosis; and (i) Autoimmune inflammatory bowel disease.
3. The use of Bromocriptine for the manufacture of a pharmaceutical composition for treating a disease selected from the group consisting of:
(a) Myasthenia gravis; (b) Endocrine opthalmopathy; (c) Grave's disease; (d) Juvenile diabetes (diabetes mellitus type 1); (e) Glomerulonephritis (with or without ne phrotic syndrome); (f) Systemic lupus erythematosus; (9) Autoimmune hematological disorder; > 45 (h) Multiple sclerosis; and (i) Autoimmune inflammatory bowel dis ease.
4. A pharmaceutical composition which in corporates Bromocriptine as active agent, for use in the treatment of a disease selected from the group consisting of:
(a) Myasthenia gravis; (b) Endocrine opthalmopathy; (c) Grave's disease; (d) Juvenile diabetps (diabetes mellitus type 1); (e) Glomerulonephritis (with or without nephrotic syndrome);; (f) Systemic lupus erythematosus; (g) Autoimmune hematological disorder; (h) Multiple sclerosis; and (i) Autoimmune inflammatory bowel disease.
5. A pharmaceutical composition according to claim 4 wherein the Bromocriptine is Bro-
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US88511086A | 1986-07-14 | 1986-07-14 |
Publications (3)
Publication Number | Publication Date |
---|---|
GB8716323D0 GB8716323D0 (en) | 1987-08-19 |
GB2192541A true GB2192541A (en) | 1988-01-20 |
GB2192541B GB2192541B (en) | 1990-05-02 |
Family
ID=25386156
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB8716323A Expired - Lifetime GB2192541B (en) | 1986-07-14 | 1987-07-10 | New use of bromocriptine |
Country Status (13)
Country | Link |
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JP (1) | JPS6323817A (en) |
KR (1) | KR880001292A (en) |
AU (1) | AU602154B2 (en) |
CH (1) | CH672987A5 (en) |
DE (1) | DE3722383A1 (en) |
DK (1) | DK363887A (en) |
FR (1) | FR2601245A1 (en) |
GB (1) | GB2192541B (en) |
IT (1) | IT1224222B (en) |
NL (1) | NL8701631A (en) |
PH (1) | PH24525A (en) |
SE (1) | SE8702843L (en) |
ZA (1) | ZA875145B (en) |
Cited By (19)
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EP0327040A2 (en) * | 1988-02-05 | 1989-08-09 | Predrag Dr.Sc. Sikiric | Use of dopamine and/or dopamine agonists to prepare a medicine for the treatment of the digestive tract |
EP0440333A2 (en) * | 1990-01-10 | 1991-08-07 | Louisiana State University Agricultural And Mechanical College | Dopamine agonists for treating type II diabetes |
US5344832A (en) * | 1990-01-10 | 1994-09-06 | The Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates |
US5468755A (en) * | 1988-05-10 | 1995-11-21 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Therapeutic process for the treatment of the pathologies of Type II diabetes |
US5626860A (en) * | 1995-06-07 | 1997-05-06 | The Board Of Supervisors Of Louisana State And Agricultural And Mechanical College | Method for regulating metabolism with dopamine beta hydroxylase inhibitors |
US5679685A (en) * | 1993-12-22 | 1997-10-21 | Ergo Science, Incorporated | Accelerated release composition containing bromocriptine |
US5688794A (en) * | 1988-05-10 | 1997-11-18 | Ergo Science Incorporated | Method for modifying or regulating lipid metalolism in an animal or human subject with a proclactin stimulating compound |
US5696128A (en) * | 1994-07-07 | 1997-12-09 | The Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method of regulating immune function |
US5700795A (en) * | 1988-05-10 | 1997-12-23 | The General Hospital Corporation | Administration of pirenzepine, methyl scopolamine and other muscarinic receptor antagonists for treatment of type II diabetes |
US5700800A (en) * | 1988-05-10 | 1997-12-23 | Ergo Science Incorporated | Methods for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates with a prolactin stimulatory compound |
US5714519A (en) * | 1995-06-07 | 1998-02-03 | Ergo Science Incorporated | Method for regulating glucose metabolism |
US5716933A (en) * | 1988-05-10 | 1998-02-10 | Louisiana State University And Agricultural And Mechanical College | Process for the long term reduction of body fat stores, insulin resistance, and hyperinsulinemia in vertebrates |
US5760047A (en) * | 1988-05-10 | 1998-06-02 | The Board Of Supervisors Of Louisiana State University And Agriculture And Mechanical College | Method for treatment of obesity using prolactin modulators and diet |
US5830895A (en) * | 1988-05-10 | 1998-11-03 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Methods for the determination and adjustment of prolactin daily rhythms |
US6004972A (en) * | 1988-05-10 | 1999-12-21 | The Board Of Supervisiors Of Louisiana State University And Agricultural And Mechanical College | Therapeutic process for the treatment of the pathologies of type II diabetes |
US6855707B2 (en) | 1996-05-07 | 2005-02-15 | Pliva D.D. | Method for the treatment of lipid and glucose metabolism disorders |
WO2008061805A1 (en) * | 2006-11-23 | 2008-05-29 | Ergonex Pharma Gmbh | Pharmaceutical compositions for the treatment of capillary arteriopathy |
US20210130344A1 (en) * | 2016-04-20 | 2021-05-06 | Veroscience Llc | Composition and Method for Treating Metabolic Disorders |
US11883399B2 (en) | 2017-10-18 | 2024-01-30 | Veroscience Llc | Bromocriptine formulations |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3814521A1 (en) * | 1987-05-07 | 1988-11-17 | Sandoz Ag | NEW APPLICATION OF DOPAMINE RECEPTOR AGONISTS |
RU2104698C1 (en) * | 1991-12-23 | 1998-02-20 | Дзе Борд оф Сьюпервайзорз оф Луизиана Стейт Юниверсити энд Эгрикалчурал энд Мекэникал Колледж | Method of treatment of pathological deviations at diabetes mellitus of type-2 |
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US3752888A (en) * | 1968-05-31 | 1973-08-14 | Sandoz Ltd | 2-bromo-alpha-ergocryptine as a lactation inhibitor |
GB2154874A (en) * | 1984-02-29 | 1985-09-18 | Sandoz Ltd | Bromocriptine compositions |
Family Cites Families (1)
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CH666406A5 (en) * | 1984-02-29 | 1988-07-29 | Sandoz Ag | METHOD FOR PRODUCING microcapsules BROMOKRIPTINMESYLAT AS PHARMACOLOGICAL ACTIVE INCLUDED. |
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1987
- 1987-07-07 DE DE19873722383 patent/DE3722383A1/en not_active Withdrawn
- 1987-07-09 CH CH2611/87A patent/CH672987A5/de not_active IP Right Cessation
- 1987-07-10 IT IT48160/87A patent/IT1224222B/en active
- 1987-07-10 NL NL8701631A patent/NL8701631A/en not_active Application Discontinuation
- 1987-07-10 FR FR8709849A patent/FR2601245A1/en not_active Withdrawn
- 1987-07-10 GB GB8716323A patent/GB2192541B/en not_active Expired - Lifetime
- 1987-07-13 KR KR1019870007490A patent/KR880001292A/en not_active Application Discontinuation
- 1987-07-13 JP JP62174576A patent/JPS6323817A/en active Pending
- 1987-07-13 DK DK363887A patent/DK363887A/en not_active Application Discontinuation
- 1987-07-13 AU AU75587/87A patent/AU602154B2/en not_active Ceased
- 1987-07-13 SE SE8702843A patent/SE8702843L/en not_active Application Discontinuation
- 1987-07-14 ZA ZA875145A patent/ZA875145B/en unknown
- 1987-07-14 PH PH35534A patent/PH24525A/en unknown
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US3752814A (en) * | 1968-05-31 | 1973-08-14 | Sandoz Ltd | 2-bromo-alpha-ergocryptine |
GB2154874A (en) * | 1984-02-29 | 1985-09-18 | Sandoz Ltd | Bromocriptine compositions |
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EP0327040A3 (en) * | 1988-02-05 | 1990-11-28 | Predrag Dr.Sc. Sikiric | Use of dopamine and/or dopamine agonists to prepare a medicine for the treatment of the digestive tract |
US5700800A (en) * | 1988-05-10 | 1997-12-23 | Ergo Science Incorporated | Methods for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates with a prolactin stimulatory compound |
US5731312A (en) * | 1988-05-10 | 1998-03-24 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Process for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates |
US5712265A (en) * | 1988-05-10 | 1998-01-27 | The General Hospital Corporation | Administration of pirenzepine, methyl scopolamine and other muscarinin receptor antagonists for treatment of glucose metabolism disorders |
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US5554623A (en) * | 1988-05-10 | 1996-09-10 | Ergo Science Incorporated | Method for the long term reduction of body fat stores, insulin resistance, hypersinsulinemia and hyperglycemia in vertebrates |
US6004972A (en) * | 1988-05-10 | 1999-12-21 | The Board Of Supervisiors Of Louisiana State University And Agricultural And Mechanical College | Therapeutic process for the treatment of the pathologies of type II diabetes |
US5635512A (en) * | 1988-05-10 | 1997-06-03 | Ergo Science Incorporated | Method for modifying or resetting the prolactin rhythm of an insulin insensitive or diabetic animal or human |
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US5688794A (en) * | 1988-05-10 | 1997-11-18 | Ergo Science Incorporated | Method for modifying or regulating lipid metalolism in an animal or human subject with a proclactin stimulating compound |
US5760047A (en) * | 1988-05-10 | 1998-06-02 | The Board Of Supervisors Of Louisiana State University And Agriculture And Mechanical College | Method for treatment of obesity using prolactin modulators and diet |
US5700795A (en) * | 1988-05-10 | 1997-12-23 | The General Hospital Corporation | Administration of pirenzepine, methyl scopolamine and other muscarinic receptor antagonists for treatment of type II diabetes |
US5854255A (en) * | 1988-05-10 | 1998-12-29 | Ergo Research Corporation | Therapeutic package for the long term reduction of body fat stores insulin resistance hyperinsulinemia and hyperglycemia in vertebrates |
US5756513A (en) * | 1988-05-10 | 1998-05-26 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Therapeutic process for the treatment of the pathologies of type II diabetes |
US5468755A (en) * | 1988-05-10 | 1995-11-21 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Therapeutic process for the treatment of the pathologies of Type II diabetes |
US5716962A (en) * | 1988-05-10 | 1998-02-10 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Process for therapeutically modifying and resetting prolactin rhythm with a dopamine agonist |
US5716957A (en) * | 1988-05-10 | 1998-02-10 | The Board Of Supervisors Of Louisiana State And Agricultural And Mechanical College | Method for modifying and resetting the bloodstream prolactin levels of a human subject |
US5716933A (en) * | 1988-05-10 | 1998-02-10 | Louisiana State University And Agricultural And Mechanical College | Process for the long term reduction of body fat stores, insulin resistance, and hyperinsulinemia in vertebrates |
US5719160A (en) * | 1988-05-10 | 1998-02-17 | The Board Of Supervisors Of Louisiana State And Agricultural And Mechanical College | Method for modifying and regulating lipid metabolism |
US5750519A (en) * | 1988-05-10 | 1998-05-12 | The Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Process for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates |
EP0440333A3 (en) * | 1990-01-10 | 1992-06-17 | Louisiana State University Agricultural And Mechanical College | Dopamine agonists for treating type ii diabetes |
US5344832A (en) * | 1990-01-10 | 1994-09-06 | The Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method for the long term reduction of body fat stores, insulin resistance, hyperinsulinemia and hyperglycemia in vertebrates |
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EP0440333A2 (en) * | 1990-01-10 | 1991-08-07 | Louisiana State University Agricultural And Mechanical College | Dopamine agonists for treating type II diabetes |
US5872133A (en) * | 1992-12-22 | 1999-02-16 | The Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method of regulating the immune response |
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US5679685A (en) * | 1993-12-22 | 1997-10-21 | Ergo Science, Incorporated | Accelerated release composition containing bromocriptine |
US5872127A (en) * | 1994-07-07 | 1999-02-16 | The General Hospital Corporation/Board Of Supervisors Of Louisiana State University | Method of regulating immune function |
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US6075020A (en) * | 1994-07-07 | 2000-06-13 | The General Hopital Corporation | Method of regulating immune function |
US5741503A (en) * | 1995-06-07 | 1998-04-21 | The Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Method for regulating metabolism with dopamine beta hydroxylase inhibitors |
US5714519A (en) * | 1995-06-07 | 1998-02-03 | Ergo Science Incorporated | Method for regulating glucose metabolism |
US5626860A (en) * | 1995-06-07 | 1997-05-06 | The Board Of Supervisors Of Louisana State And Agricultural And Mechanical College | Method for regulating metabolism with dopamine beta hydroxylase inhibitors |
US6855707B2 (en) | 1996-05-07 | 2005-02-15 | Pliva D.D. | Method for the treatment of lipid and glucose metabolism disorders |
WO2008061805A1 (en) * | 2006-11-23 | 2008-05-29 | Ergonex Pharma Gmbh | Pharmaceutical compositions for the treatment of capillary arteriopathy |
US9695173B2 (en) | 2006-11-23 | 2017-07-04 | Sinoxa Pharma Gmbh | Pharmaceutical compositions for the treatment of capillary arteriopathy |
US20210130344A1 (en) * | 2016-04-20 | 2021-05-06 | Veroscience Llc | Composition and Method for Treating Metabolic Disorders |
US11878974B2 (en) * | 2016-04-20 | 2024-01-23 | Veroscience Llc | Composition and method for treating metabolic disorders |
US11883399B2 (en) | 2017-10-18 | 2024-01-30 | Veroscience Llc | Bromocriptine formulations |
Also Published As
Publication number | Publication date |
---|---|
GB2192541B (en) | 1990-05-02 |
FR2601245A1 (en) | 1988-01-15 |
SE8702843L (en) | 1988-01-15 |
KR880001292A (en) | 1988-04-22 |
DK363887D0 (en) | 1987-07-13 |
JPS6323817A (en) | 1988-02-01 |
IT8748160A0 (en) | 1987-07-10 |
DK363887A (en) | 1988-01-15 |
SE8702843D0 (en) | 1987-07-13 |
GB8716323D0 (en) | 1987-08-19 |
IT1224222B (en) | 1990-09-26 |
CH672987A5 (en) | 1990-01-31 |
AU602154B2 (en) | 1990-10-04 |
AU7558787A (en) | 1988-01-21 |
DE3722383A1 (en) | 1988-01-28 |
NL8701631A (en) | 1988-02-01 |
ZA875145B (en) | 1989-02-22 |
PH24525A (en) | 1990-07-18 |
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