suitable compounds which have the therapeutic effect according to the invention , are compounds which have the same , but also reduced or enhanced , biological activity of vip or pacap . preferred compounds according to the invention have the same or an enhanced biological activity . all compounds falling under this group comprise the sequence arg - lys - gln - met - ala - val - lys - lys - tyr - leu ( seq id no . 4 ). the invention includes also derivatives of the disclosed peptides and polypeptides having the same biological activity . the term “ same biological activity ” means the biological , physiological or therapeutic activity or functionality compared with the relevant properties of said peptides and polypeptides , preferably vip or pacap . the term “ derivative ” means a peptide compound which derives more or less direct from the corresponding peptide , such as vip or pacap as such , and is altered by some additions , deletions , mutations or modifications without altering the biological properties of the parent peptide . suitable vip derivatives are , for example , disclosed in wo 8905857 , wo 9106565 , ep 0663406 and wo 9729126 ( fmoc protected vip ). the term includes also conjugates of peptides and polypeptides according to the invention which consist of the parent peptide or polypeptide coupled to lipophilic entities , such as liposomes . vip - liposome products are , for example , disclosed in wo 9527496 or wo 9735561 , and have improved properties with respect to bioavailability and proteolytic degradation . furthermore , the term includes also fragments , slightly modified fragments including truncated forms . the term “ analogue ” means a compound which may have a different structure and composition compared with the polypeptides and peptides according to the invention , preferably vip , however without having altered biological properties . vip analogues may be natural or synthetic peptides but also non - peptides . preferably , vip analogues according to the invention are peptides . examples for known vip analogues are disclosed in ep 0325044 ( cyclic peptides ), ep 0225020 ( linear peptides ), ep 0536741 ( cyclic vip modifications ), ep 0405242 , ep 0184309 and ep 0613904 . the term includes also vip or pacap homologues , which are not vip or pacap but show great structural similarity to vip . such a vip homologue according to the invention is pacap itself and its truncated form pacap - 27 . the term also includes such homologues which could form , like vip , amphipathic helices . preferred vip / pacap homologues are peptides that comprise one or more consensus sequences . examples are peptide histidine isoleucine ( phi ), peptide histidine methionine ( phm ), human growth hormone releasing factor ( grf ), pituitary adenylate cyclase activating peptide ( pacap ), secretin and glucagon . the term “ stabilized form ” means a derivative or analogue wherein the parent peptide was altered in order get more stability and increased half - life in blood and serum . such stabilized forms are preferred if the polypeptide is fragmented by enzyme activity . possible stabilized forms are cyclic peptides or polypeptides like cyclic vip or vyclic pacap , fusion proteins , preferably fc - fusion proteins or pegylated polypeptides , for example pegylated vip or pacap . methods for manufacturing such polypeptides are well known in the art . polypeptides and proteins may be protected against proteolysis by the attachment of chemical moieties . such attachment may effectively block the proteolytic enzyme from physical contact with the protein backbone itself , and thus prevent degradation . polyethylene glycol is one such chemical moiety which has been shown to protect against proteolysis ( sada , et al ., j . fermentation bioengineering 71 : 137 - 139 , 1991 ). in addition to protection against proteolytic cleavage , chemical modification of biologically active proteins has been found to provide additional advantages under certain circumstances , such as increasing the stability and circulation time of the therapeutic protein and decreasing immunogenicity . ( u . s . pat . no . 4 , 179 , 337 ; abuchowski et al ., enzymes as drugs ; j . s . holcerberg and j . roberts , eds . pp . 367 - 383 , 1981 ; francis , focus on growth factors 3 : 4 - 10 ; ep 0 401 384 ). the addition of polyethylene glycol increases stability of the peptides and polypeptides of this invention at physiological ph as compared to non - pegylated compounds . the pegylated polypeptide / protein is also stabilized with regard to salts . the term “ fusion protein ” means a compound , especially a stabilized form , consisting of a polypeptide according to the invention , preferably vip or a vip derivative or analogue , such as pacap , which is fused to another peptide or protein . such a protein is preferably an immunglobulin molecule , more preferably a sent thereof , most preferably a fc portion of an igg molecule , preferably an igg1 . a fc - vip fusion protein is described in wo 200024278 and shows an improved half - life in serum and blood . a further example is fc - pacap and fc - pacap - 27 . the compound according to the invention can be used as medicament or as diagnostic means to evaluate pathological conditions in an individual . the term “ individuar ” preferably refers to mammals , especially humans . the compound is used in a pharmaceutical composition and formulations , comprising , as a rule , a pharmaceutically acceptable carrier , excipient or diluents . techniques for the formulation and administration of the compounds of the present invention may be found in “ remington &# 39 ; s pharmaceutical sciences ” mack publishing co ., easton pa . as used herein , the term “ pharmaceutically acceptable carrier ” means an inert , non toxic solid or liquid filler , diluent or encapsulating material , not reacting adversely with the active compound or with the patient , or any other formulation such as tablets , pills , dragees , capsules , gels , syrups , slurries , suspensions and the like . suitable , preferably liquid carriers are well known in the art such as sterile water , saline , aqueous dextrose , sugar solutions , ethanol , glycols and oils , including those of petroleum , animal , vegetable , or synthetic origin , for example , peanut oil , soybean oil and mineral oil . the formulations according to the invention may be administered as unit doses containing conventional non - toxic pharmaceutically acceptable carriers , diluents , adjuvants and vehicles which are typical for parenteral administration . the term “ parenteral ” includes herein subcutaneous , intravenous , intra - articular and intratracheal injection and infusion techniques . parenteral compositions and combinations are most preferably administered intravenously either in a bolus form or as a constant fusion according to known procedures . also other administrations such as oral administration or administration by inhalation or nasal spray are suitable . tablets and capsules for oral administration contain conventional excipients such as binding agents , fillers , diluents , tableting agents , lubricants , disintegrants , and wetting agents . the tablets may be coated according to methods well known in the art . for inhalations the compound according to the invention is preferably brought in an aerosol form . aerosols and techniques to make them are well known in the art . aerosols applicable by inhalers containing a peptide or polypeptide of the invention , for example , vip or pacap are preferred if direct pulmonary symptoms have to be treated . unit doses according to the invention may contain daily required amounts of the compound according to the invention , or sub - multiples thereof to make up the desired dose . the optimum therapeutically acceptable dosage and dose rate for a given patient ( mammals , including humans ) depends on a variety of factors , such as the activity of the specific active material employed , the age , body weight , general health , sex , diet , time and route of administration , rate of clearance , enzyme activity , the object of the treatment , i . e ., therapy or prophylaxis and the nature of the disease to be treated . therefore , in compositions and combinations in a treated patient ( in vivo ) a pharmaceutical effective daily dose of the compound of this invention is between about 5 ng and 200 μg / kg body weight , preferably between 20 ng and 20 μg / kg body weight . surprisingly , it was found that the peptides and polypeptides as defined above and in the claims , above all vip and pacap , have beneficial effects in the treatment of sarcoidosis as demonstrated in the following example . these data show a dramatic improvement for the treatment of as yet not sufficiently treatable diseases . it is a benefit of this invention that all tested polypetides comprising the highly conservative decapeptide sequence as depicted in above are efficacious . a patient with severe sarcoidosis stadium 3 and secondary pulmonary hypertension was under therapy with cortocosteroids , furosemid , oxygen and an anticoagulant . right heart catheterization ( swan - ganz , baxter , irvine , calif ., usa ) was performed to measure mean pulmonary artery pressure ( mpap ), cardiac output ( co ), mean arterial pressure ( map ), pulmonary capillary wedge pressure ( pcwp ) mixed venous oxygen saturation ( svo 2 %) and systemic arterial oxygen pressure ( pao 2 %) for and after treatment with vip inhalation ( 200 μg in 12 ml 0 , 9 % nacl per day , 4 × 3 ml per inhalation ) for 12 weeks . fev1 ( forced expiratory volume in one second ), fvc ( forced vital capacity ), tlc ( total lung capacity ), aado2 ( arterial - alveolar oxygen difference ) of sarcoidosis patient is measured according to standard methods for and after treatment with vip ( 200 μg in 12 ml 0 , 9 % nacl per day ) for 12 weeks . vip was inhaled for 12 weeks via the microdrop master jet ( mpv , truma , germany ) using a particle size of 3 μm to provide alveolar deposition of the substance . hemodynamic and lung function parameters of the sarcoidosis patient before and after the treatment with vip for 12 weeks are summarized in table 2 . in the 6 - minutes walk test , the patient improved from 210 meters before treatment to 350 meters after the treatment . 4 . crystal r g , bitterman p b , rennard s l hance a j , keogh b a . interstitial lung diseases of unknown cause . disorders characterized by chronic inflammation of the lower respiratory tract ( first of two parts ). n engl j med 1994 ; 310 : 154 - 66 . 5 . staton g w jr , ingram r h jr . chronic diffuse infiltrative lung disease . in : dale d c , federman d d , eds . scientific american medicine . new york : scientific american , 1997 : 11 - 24 . 6 . winterbauer r h , hutchinson j f . use of pulmonary function tests in the management of sarcoidosis . chest 1980 ; 78 : 640 - 7 . 7 . muther r s , mccarron d a , bennett w m . renal manifestations of sarcoidosis . arch intern med 1981 ; 141 : 643 - 5 . 9 . sharma o p , maheshwari a , thaker k myocardial sarcoidosis . chest 1993 ; 103 : 253 - 8 . 10 . eklund a g . sarcoidosis . in : rakel r e , ed . conn &# 39 ; s current therapy , 1997 : latest approved methods of treatment for the practicing physician . philadelphia : saunders , 1997 : 229 - 31 .
the present invention relates to peptides which arm highly biologically and pharmacologically active as therapeutic drug for the treatment of diseases related to sarcoidosis . the peptides which can be used according to the invention for the treatment of said disease comprise at least one specific highly conservative amino acid residue sequence which seem to play an important role in connection with pulmonary and arteriolar hypertension events . it could be shown that the known naturally occurring peptides “ vasoactive intestinal peptide ” and “ pituitary adenylate cyclase - activating polypeptide ”, having these specific sequences are potent drugs which can be successfully used for treatment of sarcoidosis . furthermore , the present invention discloses a method for the treatment patients suffering from sarcoidosis .