AU2010345621B2 - Use of pentoxifylline for preventing or treating constipation - Google Patents

Abstract

Use of pentoxifylline in preparation of medicaments for preventing or treating constipation, a pharmaceutical composition comprising pentoxifylline for preventing or treating constipation and a method for treating constipation by using pentoxifylline are disclosed. The trial of the present invention proves that pentoxifylline can improve constipation, especially functional constipation.

Description

Use of Pentoxifylline for Preventing or Treating Constipation TECHNICAL FIELD This invention relates to the field of pharmaceutics, and particularly relates to novel use of pentoxifylline, specifically to use of pentoxifylline in the preparation of medicaments for preventing or treating constipation, a pharmaceutical composition comprising pentoxifylline for preventing or treating constipation, and a method for preventing or treating constipation by using pentoxifylline. Particularly, said constipation is functional constipation. BACKGROUND ART Phosphodiesterases (PDEs) have the function of hydrolyzing intracellular second messengers of cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP), and terminating the biochemical actions mediated by these second messengers by degrading the intracellular cAMP or cGMP. The cAMP and cGMP play important roles in regulating cellular activities. The regulation of the concentrations of cAMP and cGMP mainly depends on the balance between the synthetic effect of nucleotide cyclase and the hydrolytic effect of PDEs. PDEs are widely distributed over human body with physiological effects concerning a number of research fields. Recently, PDEs, as a new target for treatment, have drawn wide attentions from many scholars, and become a new hot topic of research. PDE inhibitors belong to a big multi-gene family and are the agents for inhibiting the activities of PDEs. They are compounds capable of inhibiting the degradation of cAMP and cGMP in tissues. PDE inhibitors include non-specific and specific PDE inhibitors. The specific PDE inhibitors can only inhibit one kind of PDEs while have little effect on the other kinds. The non-specific PDE inhibitors include theophylline, aminophylline, pentoxifylline, pargeverine, caffeine and the likes. Theophylline is a white, amorphous and crystalline alkaloid comprised in teas. It is an isomer of theobromine and has similar structure and functions as caffeine. As a PDE inhibitor, theophylline can increase cAMP content in cells, relax smooth muscles, excite myocardium and exert diuresis effects. Aminophylline is a double-salt preparation of theophylline and ethylenediamine, which has been widely used in clinic for many years in China. Compared with theophylline, aminophylline has higher water solubility and is easy to be dissolved and absorbed. However, due to the strong alkalinity and high local stimulation, the oral administration of aminophylline frequently leads to gastrointestinal reactions such as nausea, vomiting, loss of appetite and the likes. Pargeverine is a skeletal muscle relaxant. Caffeine is an alkaloid extracted from teas or coffee berries. The appropriate use of caffeine may dispel fatigue and excite nerve system. Caffeine is used clinically for treating neurasthenic and for recovery from coma. Pentoxifylline (PTX) is an alkaloid obtained by incorporating a hexanone group into theobromine extracted from cocoa beans. Its molecular formula is C 13

H

2 0

N

4 0 3 and the chemical name is 3,7-dimethyl xanthine. It is a derivative of methyl xamthine and functions as a non-specific PDE inhibitor. PTX can increase the deformability of erythrocytes, improve the blood rheology properties of leukocytes, inhibit the adhesion and activation of neutrophils, expand micro-vessels, reduce blood viscosity and increase oxygen partial pressure in tissues. PTX has anti-inflammatory effects and can eliminate free radicals. In 1960's, PTX was used merely in the treatment of peripheral circulation disorders, and later as a vasodilator for treating vascular diseases for more than 10 years. It has also been used in the treatment of peripheral vascular diseases, such as atherosclerosis, thrombosis, diabetic vasculopathy, chilblains, venous ulcers and the likes. In 1970's, PTX began to be used in the treatment of male sterility and in vitro stimulation of sperm activity, and showed significant therapeutic effects. Furthermore, PTX also has efficacy on the obstruction of inner ear microcirculation, can prevent hepatic fibrosis, and has protective effects on kidney, lung, etc. The function of PTX in the promotion of learning and memory has been disclosed in "Pentoxifylline Promotes Learning and Memory Function of Aging Rats and Mice with Induced Memory Impairment", Journal of Southern Medical University, No.11, Vol.27, 2007 in details. "Studies on Radiosensitization By Pentoxifylline In Human Hepatoma Cell Lines and its Mechanism" disclosed that PTX exhibited cytotoxicity in a dose-dependent manner following a 48-hour treatment on human hepatoma cell lines HepG2 and Hep3b, with an optimum concentration at 2mmol/L. PTX has good intestinal absorption and a half-life of 30 min in plasma. Generally, PTX is metabolized in liver by demethylation and oxidation, and excreted mainly in two forms of 3-methyl purine and 7-methyl purine. -Constipation, especially chronic constipation, is a common symptom with complex pathogenesis. Constipation brings much distress to patients, and seriously affects the life quality of the patients. Along with the development of society, increase of life stress, intense competition and change of living habits such as diet, incidence of constipation is increasing. Rome I and Rome II criteria were internationally introduced in 1994 and 2000, respectively, for the diagnosis, pathophysiology and treatment of functional gastrointestinal disorders including constipation. Rome II criteria is adopted internationally as a common criteria for the definition of constipation, i.e. constipation is characterized by hard stools, a sense of difficulty passing stools or incomplete evacuation and infrequent stools. Based on the etiologies, the chronic constipation can be divided into organic constipation and functional constipation. Generally, the organic constipation is the ones caused by organic etiologies. The organic etiologies for chronic constipation are mainly gastrointestinal diseases (intestinal tumors, congenital megacolon, etc.), perianal diseases (rectal prolapse, anterior rectocele), nervous system diseases (multiple sclerosis, Parkinson's disease, stroke, spinal cord injury and peripheral neuropathy), endocrine or metabolic diseases (diabetic enteropathy, hypothyroidism, parathyroid diseases) and psychosis. Meanwhile, the constipation caused by drugs (opioids, anticholinergic agents, antidepressants, antagonists of calcium channels, antacids, ferralias, anti-diarrheal agents, diuretics, antihistamines, etc.) are excluded. 2 The functional constipation is the constipation other than those caused by organic etiologies and other factors, and complies with the following criterion: having two or more of the following symptoms for at least 12 weeks, which need not be consecutive, in the preceding 12 months: (1) straining in one-fourth of defecations; (2) lumpy or hard stools in one-fourth of defecations; (3) sensation of incomplete evacuation in one-fourth of defecations; (4) sensation of obstruction/blockage of the anus in one-fourth of defecations; (5) use of manual maneuvers to facilitate in one-fourth of defecations (pelvic floor dysfunctional diseases), and (6) less than three defecations per week. According to the blockage sites and motility dysfunction, the functional constipation can be generally divided into three types: slow transit constipation (STC), outlet obstructive constipation (OOC), and mixed constipation (MIX). STC is a common type of functional constipation, accounting for 40% of the cases. OOC usually occurs in children, women and the elderly. STC is related with the colonic motility disorders. The Bangkok new classification for disorders of gastrointestinal motility clearly indicates that intestinal neuropathy, intestinal myopathy, Parkinson's disease, endocrine disease, or spinal cord injury can lead to delayed colonic transit and STC in turn. Patients with STC have decreased amounts of the interstitial cells of Cajal (ICC) with reduced sizes. The decrease of ICC is thus considered as the main intestinal histocytological character of STC. As a proto-oncogene, c-kit locates on the W locus of Chromosome 5, and codes for a kit receptor, which belongs to tyrosine kinase membrane receptors. By expressing c-kit, ICC can receive a variety of signals via the receptor. If the c-kit receptor is blocked, not only the development but also the functions of ICC are affected. Hence, the expression of c-kit in ICC is closely related with intestinal motility. The ICC can be identified with anti-c-kit antibodies. OOC is related with the lack of coordination of anal sphincter functions or to the abnormal threshold of the sense of rectal defecation reflex. The chief complaints of OOC patients often include straining, sensations of anal tenesmus and incomplete evacuation, infrequent stools, hard or soft-formed stools. Mixed constipation has both of the above characters. Since each kind of constipations has different pathogenesis, the complaints of the patients about constipations should be paid more attention and analyzed in details for the initial classification and the appropriate therapy. The special lesion parts and pathogenesis of functional constipation make its clinical treatment very difficult. Common drugs currently used for constipation are undesirable in the respects of therapeutic effects, long course of treatment, ineffective or only a few of loose stools defecated or serious side-effects unbearable by the patients. Currently, non-drug and drug therapies are used in clinic. Surgeries may also be required for the severe cases. Most of non-drug therapies, for example the guidance on . defecation patterns, improvement of lifestyle such as diets, biofeedback therapy and the likes, need a long term for alleviation. Many patients cannot adhere to the therapy due to personal factors. The main drugs for constipation include irritant cathartics, emollient cathartics, bulk cathartics and osmotic laxatives, prokinetic drugs and the likes. Irritant cathartics have strong and rapid effects and are used mostly in patients with obstructed stools and needs of rapid 3 catharsis. However, the irritant cathartics are not suitable for long-term use, since they stimulate intestinal mucosa and intestinal plexus, increase mucosal permeability, affect or even disrupt the absorption of water, electrolytes and vitamins by intestine, and can lead to large intestine myasthenia, drug dependency and fecal incontinence. Bulk cathartics can 5 increase the volume of stools, but cannot effectively increase the tension of colon. The use of bulk cathartics in patients with slow intestinal movement is thus restricted. Emollient cathartics have poor taste and weak effects, and may cause adverse reactions such as malabsorption of fat-soluble vitamins, and perianal oil spillage in long-term use. Osmotic cathartics, such as lactulose, are not absorbed by small intestine. Instead, they exert the effects 10 in colon upon degradation by colonic bacteria to release organic acids. Osmotic cathartics have disadvantages, such as abdominal distension or pains, and poor therapeutic effect and tendency to change intestinal flora in long-term use. Prokinetic drugs often require to be combined with other drugs, and have greater side effects. For OOC which accounts for more than 50% of functional constipation, sustained cramp 15 and increased pressure of internal and external anal sphincter are of the main pathophysiological changes. OOC is treated mainly by therapies such as surgery, biofeedback and the likes for relieving the symptom of anorectal outlet obstruction by reducing the pressure of anal sphincter. Despite a number of therapies existed, the therapeutic effects are not satisfied. Surgeries have long course and large wounds, and may encounter complications 20 such as anal incontinence, recurrence and the likes. Biofeedback therapies often require long course and repeated treatments with uncertain therapeutic effects. In recent years, it has conceived of the use of various drugs for reducing the pressure of anal sphincter, so as to achieve the treatment of outlet obstruction constipation. 25 SUMMARY OF THE INVENTION The present invention provides novel use of pentoxifylline in the field of pharmaceutics, and particularly relates to use of pentoxifylline in the preparation of medicaments for preventing or treating constipation, a pharmaceutical composition comprising pentoxifylline for preventing or treating constipation, and a method for preventing or treating constipation 30 by using pentoxifylline. Particularly, said constipation is functional constipation. As a non-specific PDE inhibitor, pentoxifylline is mainly used in the treatments of thromboangiitis obliterans, cerebrovascular disorders, vascular headache, peripheral vascular disease, cochlear disrupt disease, chilblain and pains caused by hypoxia. Although pentoxifylline may cause adverse reactions such as constipation, dry mouth and the likes in clinic uses, the present 35 inventor surprisingly finds by experiments that pentoxifylline exhibits unexpected effects in the treatment of constipation, especially functional constipation. In a first aspect there is provided the use of pentoxifylline in the preparation of a 4 medicament for preventing or treating functional constipation. In one embodiment the medicament is a pharmaceutical composition comprising pentoxifylline. In a second aspect there is provided a method for treating functional constipation, comprising the step of administering a therapeutically effective amount of a pharmaceutical 5 composition comprising pentoxifylline to a patient. In one embodiment the pharmaceutical composition is the pharmaceutical composition of the first aspect. It is to be noted that, throughout the description and claims of this specification, the word 'comprise' and variations of the word, such as 'comprising' and 'comprises', is not intended to exclude other variants or additional components, integers or steps. Modifications and 10 improvements to the invention will be readily apparent to those skilled in the art. Such modifications and improvements are intended to be within the scope of this invention. Any reference to or discussion of any document, act or item of knowledge in this specification is included solely for the purpose of providing a context for the present invention. It is not suggested or represented that any of these matters or any combination 15 thereof formed at the priority date part of the common general knowledge, or was known to be relevant to an attempt to solve any problem with which this specification is concerned. There was no report of the studies on the treatment of functional constipation with pentoxifylline. Surprisingly, the present inventor finds by experiments that pentoxifylline has unexpected effects in the improvement of constipation, in particular functional constipation, 20 indicating that pentoxifylline can be used as a medicament for treating constipation. 4a According to one aspect, the present invention provides a pharmaceutical composition comprising pentoxifylline for preventing or treating constipation (especially functional constipation). The pharmaceutical composition comprising pentoxifylline can be formulated into topical preparations for external uses, or oral preparations with conventional techniques. The topical preparations for external uses are preferably those suitable for anorectal administration, such as sprays, aerosols, suppositories, gels, pastes, creams, ointments, solutions, emulsions and liposome preparations. The oral preparations are preferably conventional tablets, capsules, dropping pills, granules, powders and oral solutions. The present invention further optimizes the content of pentoxifylline in the topical preparations for external uses. Preferably, pentoxifylline is present in an amount of 0.1%- 10% by weight based on the topical preparation. The excipients comprised in said topical preparations of the pharmaceutical compositions may be one or more selected from: semi-synthetic fatty acid glyceride, Carbomer, triethanolamine, sodium lauryl sulfate, liquid paraffin, glycerol mononitrate, p-hydroxyl benzoic acid, animal and vegetable oils, Vaseline, cellulose derivatives, polyethylene glycol, silicone, silicic acid, aluminum stearate, propylene glycol, lanolin, beeswax, talc powder and zinc oxide. The excipients for sprays may be one or more selected from: lactose, talc powder, glycerol, sodium chloride and urea. The sprays may further comprise conventional propellants, such as chloro-fluoro hydrocarbons and/or volatile non-substituted hydrocarbons. The volatile non-substituted hydrocarbons are preferably butane and propane. The liniments or drops for external uses can be formulated with water- or oil-based matrix by conventional methods. The excipients for said topical preparations of the pharmaceutical compositions may further include one or more preservatives, such as chlorhexidine acetate, benzalkonium bromide and the likes. The topical preparations may be manufactured by mixing pentoxifylline with the excipients under sterile conditions. Preferably, the topical preparations may further comprise propellants. Said* topical preparations of the pharmaceutical composition are preferably in transmucosal dosage forms, which may be formulated with mucosal adhesive polymers, thereby delaying the release of the effective ingredients in the anal mucosa. The transmucosal dosage form can rapidly disintegrate and/or dissolve to achieve topical or systemic absorption, while keeping in contact with the mucosa. The transmucosal drug delivery allows the active ingredient to effectively enter into systemic circulation, and reduces the immediate metabolism of the drug by liver and the flora on the intestinal wall. Preferably, said topical preparation is a suppository or aerosol. The suppository may comprise polysorbate 80, glycerol and gelatin. The aerosol may comprise Freon F 12 , glycerol, benzalkonium bromide and urea. When the pharmaceutical composition comprising pentoxifylline is an oral preparation, the pharmaceutical composition preferably comprises 10mg to 100mg of pentoxifylline. More preferably, the pharmaceutical composition is in the form of tablets, granules or capsules 5 comprising 10mg to 100mg of pentoxifylline. When the pharmaceutical composition is in the form of a tablet comprising 10mg to 100mg of pentoxifylline, it may be a conventional tablet, an enteric-coated tablet or a sustained release tablet. The person skilled in the art understands that in comparison with the other tablets dosage-forms, the conventional tablet requires only conventional reagents for preparations. The enteric-coated tablet has isolating coatings and enteric coatings applied on the outside of a conventional tablet for protecting stomach from stimulation. The coatings are dissolved and release the active agent upon entering into the intestinal tract. The sustained-release tablet is prepared by special pharmaceutical materials for reducing administration frequency and decreasing the releasing rate of the drugs. When the pharmaceutical composition is in the form of a conventional tablet, it may consist of pentoxifylline and excipients. The excipients may include diluents, binders and disintegrating agents. The diluents may be one or more selected from starch, dextrin, lactose and microcrystalline cellulose. The binders may be one or more selected from hydroxypropyl cellulose, ethyl cellulose, carboxymethyl cellulose sodium and polyvinyl pyrrolidone. The disintegrating agents may be one or more selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and cross-linked polyvidone. Preferably, the excipients of said conventional tablet may further include wetting agents and/or lubricants. The wetting agents may be selected from water, ethanol or mixtures thereof. The lubricants may be one or more selected from magnesium stearate, zinc stearate and micronized silica gel. Preferably, pentoxifylline in one conventional tablet is in an amount of 10 mg, 25 mg, 50 mg or 75 mg. The optimization of the pentoxifylline content in the conventional tablets is generally based on the content specification of the conventional tablets with better therapeutic effects in the treatment of functional constipation. When said pharmaceutical composition is in the form of an enteric-coated tablet, it may consist of a pentoxifylline tablet, an isolating layer and an enteric coating layer. The pentoxifylline tablet may be any one of the above conventional pentoxifylline tablets. The enteric-coated pentoxifylline tablet may be prepared by coating a conventional pentoxifylline tablet sequentially with a solution of film coating powder and then a solution of enteric coating powder. Preferably, the diluents in the pentoxifylline tablet may be selected from lactose and microcrystalline cellulose. The wetting agents may be selected from ethanol solution. The binders may be one or more selected from hydroxypropyl methyl cellulose, ethyl cellulose, carboxymethyl cellulose sodium and polyvinyl pyrrolidone. The disintegrating agents may be one or more selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, and cross-linked polyvidone. The lubricants may be selected from magnesium stearate. Preferably, pentoxifylline in one enteric-coated tablet is in an amount of 25 mg or 50 mg. The optimization of the pentoxifylline content in the enteric coated tablets is generally based 6 on the content specification of the enteric coated tablets with better therapeutic effects in the treatment of functional constipation. When said pharmaceutical composition is in the form of a sustained-release tablet, it may be a matrix tablet prepared with pentoxifylline, excipients and one or more inert solid matrix materials by compression or fusion techniques. The commonly-used matrix materials include hydrophilic gel matrix materials, bio-erodible matrix materials and insoluble matrix materials. The hydrophilic gel matrix material may be one or more selected from hydroxypropyl methyl cellulose, Carbomer, sodium alginate, methyl cellulose and carboxymethyl cellulose sodium. The hydrophilic gel matrix materials expand upon exposure to water or gastrointestinal fluid to form a gel barrier for controlling the release of drugs. The bio-erodible matrix materials include triglycerides, hydrogenated castor oil, stearyl alcohol, stearic acid, Carnauba wax, stomach-soluble or enteric acrylic resins, enteric celluloses and the likes. The insoluble matrix materials may be water-insoluble polymers, including ethyl cellulose, acrylic resins (for example permeable acrylate, such as methacrylate-methyl acrylate copolymer), mixtures thereof, or the likes. Once the gastrointestinal fluid permeates into pores of the matrix, the drug is dissolved, slowly diffuses and releases via fine holes present in the matrix. Preferably, a variety of matrix materials with different solubility and erosion properties may be used as the matrix materials in the sustained-release pentoxifylline tablet. The excipients in the sustained-release pentoxifylline tablet may be one or more selected from diluents, wetting agents, binders, disintegrating agents and lubricants. The diluents may be one or more selected from starch, dextrin, lactose and microcrystalline cellulose. The wetting agents may be selected from water, ethanol or mixtures thereof. The binders may be one or more selected from hydroxypropyl methyl cellulose, ethyl cellulose, carboxymethyl cellulose sodium and polyvinyl pyrrolidone. The disintegrating agents may be one or more selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose and cross-linked polyvidone. The. lubricants may be one or more selected from magnesium stearate, zinc stearate and micronized silica gel. Preferably, pentoxifylline in one sustained-release tablet is in an amount of 75 mg or 80 mg. The optimization of the pentoxifylline content in the sustained-release tablets is generally based on the content specification of the sustained-release tablets with better therapeutic effects in the treatment of functional constipation. According to another aspect, the present invention provides use of pentoxifylline in the preparation of medicaments for preventing or treating constipation, especially functional constipation. Preferably, the medicament is the pharmaceutical composition of the present invention described above. According to a further aspect, the present invention provides a method for treating constipation (especially functional constipation), wherein the method comprises administering a therapeutically effective amount of a pharmaceutical composition comprising pentoxifylline to the subject/patient. Preferably, an effective amount of said pharmaceutical composition of 7 the present invention may be administered to the patient via oral or topical (external) administration. For example, the pharmaceutical composition of the present invention may be applied to the corresponding anorectal areas or diseased anal tissues, such as external anal tissues or internal anal tissues or proctodaeum. According to the present invention, an effective amount of the pharmaceutical composition of the present invention is preferably applied directly to the anorectal areas of the patients with functional constipation. Thus, the topical preparations of pentoxifylline are preferred, including suppository, aerosol, ointment and the likes. Before the administration of the topical preparation, the anal areas should be cleaned to facilitate the absorption of the preparation from the rectal mucosa. The subject with functional constipation to be treated by pentoxifylline includes human or animals. The specific dosage of pentoxifylline depends on a number of factors known by the skilled in the art, such the specific dosage form, the condition, age, body weight, and clinical situation of the subject to be treated. Based on the pentoxifylline used, administration routes and the likes, the dosage range may vary as follows: (1) For adults: the oral preparations include tablets, capsules, enteric-coated tablets, drops, granules, powder and oral solution. Based on the amount of pentoxifylline, the dosage for oral administration for may be from 10 mg to 100 mg for each time with one to three times each day. The topical preparations include spray, suppository, gel, paste, cream, ointment, solution, emulsion and liposome preparation. The dosage for topical administration may be the same as that for oral administration based on the amount of pentoxifylline. The administration frequency may be determined specifically according to clinical symptoms and the degree of alleviation. (2) For children: the oral preparations include tablets, capsules, enteric-coated tablets, drops, granules, powder and oral solution. Based on the amount of pentoxifylline, the dosage for oral administration for may be from 10 mg to 100 mg for each time with one to three times each day. The topical preparations include spray, suppository, gel, paste, cream, ointment, solution, emulsion, and liposome preparation. The dosage for topical administration may be the same as that for oral administration based on the amount of pentoxifylline. The administration frequency may be determined specifically according clinical symptoms and the degree of alleviation. (3) For infants less than 3 years old or animals including pig, dog, sheep, cow, tiger and the likes: the effective dosage of the oral preparations or topical preparations may be appropriately adjusted by the person skilled in the art in accordance with the dosage for children. The present invention further provides the experimental researches on the pharmaceutical composition comprising pentoxifylline according to the present invention in the treatment of functional constipation. In Experimental Example 1 of the present invention, a mouse model of slow transit constipation was induced and established by the subcutaneous injection of morphine. The stool weights of mice were recorded. The colonic transit function of the mice in the test groups was compared with that of the mice in the control group by the 8 test of activated carbon gavage. The areas of c-kit positive cells were determined by immunohistochemical technique and the amounts of Cajal cells (ICC) in colonic tissues of the two groups were compared. After administration, the mice in the model control group had decreased stools, reduced intestinal propulsion (i.e. delayed time of first black feces excretion), and decreased ICCs in intestinal tract (i.e. decreased area of c-kit positive cells), which were significantly different from those of the normal group. After administration of the non-specific PDE inhibitors of pentoxifylline, theophylline, aminophylline, caffeine and pargeverine, the results showed that mice in the pentoxifylline-treated groups (including the tablet group and the suppository group) had increased average daily stool amounts, strengthened intestinal propulsion, and increased ICC cells in intestinal tract. The results also showed that pentoxifylline has unexpected effects on the improvement of the symptoms of the slow transit constipation. The efficiency of the other non-specific PDE inhibitors of theophylline, aminophylline, caffeine and pargeverine was much lower than pentoxifylline in the treatment of functional constipation. Moreover, the inventor surprisingly finds that compared with the group of pentoxifylline tablet, the group of pentoxifylline suppository exhibited significant difference in terms of the average daily stool amounts, the time of first black feces excretion and the area of c-kit positive cells (p<0.05), indicating that the therapeutic effect of direct administration of pentoxifylline via rectal mucosa is better than that of oral administration in the treatment of the slow transit constipation. For outlet obstruction constipation which accounts for more than 50% of the functional constipations, sustained cramp and increased pressure of internal and external anal sphincter are of the main pathophysiological changes. According to Experimental Example 2 of the present invention, the anorectal resting pressure, maximum autonomic systolic pressure and the value of rectoanal inhibitory reflex in the groups treated with pentoxifylline were significantly decreased, demonstrating that the muscle tone of the anal sphincter was effectively reduced and the effect of relaxing anal sphincter was achieved. The observation of histopathological sections showed that anal sphincter fibers of mice in the pentoxifylline-treated groups atrophied to a certain extent. Pentoxifylline can effectively reduce the pressure of anal sphincter, provides a novel method and approach for the clinical treatment of chronic outlet obstruction constipation, and thus is worthy of further study. In Experimental Example 3 of the present invention, the effects of pentoxifylline on rectal mucosal mucus of rats with Loperamide-induced constipation were determined. The results showed that the epithelial mucus from the intestinal mucosa of the rats with Loperamide-induced constipation was significantly reduced compared normal rats, while the intestinal mucosal epithelial mucus increased significantly after the administration of pentoxifylline with statistical differences. Compared with pentoxifylline gavage group, the intestinal mucosal epithelial mucus of the rats in the topical administration group significantly increased with statistical differences (p <0.05), indicating that rectal administration is more effective on enhancing the functional effect of intestinal mucosa. The fluid excreted by the normal colonic mucosal goblet cells is rich in mucin, which 9 forms mucus by combining with water. The mucus barrier thus constructed has a mechanically protective effect for the mucosa. The reduction of mucus secretion reflects the weakness of colonic function, or the reduction of water retention, or reduced mucin secretion from the cells. By the administration of pentoxifylline, the inventor surprisingly finds that pentoxifylline has unexpected effects on the improvement of colonic function and the increase of the normal mucus secretion by intestinal mucosa. It can be seen that in the treatment of the functional constipation, pentoxifylline improves not only the symptoms of functional constipation but also the function of intestinal mucosa, and thus may achieve the significant improvement of functional constipation. As a medicament for the treating functional constipation, the topical preparations of pentoxifylline are generally superior to the oral preparations. However, in consideration of the advantages of convenient administration, the development of the oral preparations of pentoxifylline for the treating functional constipation is feasible. In Experimental Example 4, a clinical experiment was carried out on the tablets of the pharmaceutical composition comprising pentoxifylline for treating functional constipation. The results showed that the symptoms of volunteers with functional constipation were significantly alleviated in the conventional tablet groups (10mg, 50mg and 80mg), sustained-release tablet groups (75mg and 100mg) as well as the enteric-coated tablet groups (10 mg and 50 mg). The effective rates were 58.33% to 87.50%, and the average total effective rate was 77.38%. The incidences of adverse reactions were low (0% to 8.33%), and the average incidence of adverse reactions was 2.08%. In contrast, the effective rates of the 400mg sustained release tablet group and the 120mg enteric-coated tablet group were 41.67% to 50.00%, and the average effective rate was 45.83%; the incidences of adverse reactions were relative higher (12.50% to 33.3%) and the average incidence of adverse reactions was 22.92%; there were cases with symptoms of functional constipation deteriorated. It can be seen that compared with the groups of tablets comprising higher dosages of pentoxifylline, the groups of the tablets comprising lower dosages (10mg to 100mg) of pentoxifylline have higher effective rates and lower incidences of adverse reactions in the treatment of functional constipation with statistical differences. The tablets comprising lower dosage (10mg to 100mg) of pentoxifylline according to the present invention can be used as a medicament for treating functional constipation. The skilled person in the art could envisage that granules or capsules of the pharmaceutical composition comprising 10 mg to 100 mg of pentoxifylline can achieve the same or similar effects as the tablets of the pharmaceutical composition comprising 10 mg to 100 mg of pentoxifylline. This further demonstrates that the pharmaceutical compositions comprising 10 mg to 100 mg of pentoxifylline can be used as a medicament for treating functional constipation. EMBODIMENTS FOR CARRYING OUT THE INVENTION The present invention is further described hereafter with reference to the following 10 examples and experimental examples. The present invention is not limited to these examples. I. Pharmaceutical preparations of pentoxifylline Example 1 - Pentoxifylline suppository Pentoxifylline 45 g Polysorbate-80 5 g Glycerol 3000 g Gelatin 900 g Purified Water to 4500 g Preparing process: The indicated amount of gelatin was weighed and added into a container. To the container, an appropriate amount of purified water was added and then stood for about 1 hour to allow gelatin to be swelled and softened. An indicated amount of glycerol was then added, and the mixture was heated in a water bath to dissolve gelatin. Pentoxifylline and polysorbate 80 were mixed and then added into the solution of glycerol and gelatin under continuous heating and stirring. Upon evenly stirring, the hot mixture was poured into a suppository mold coated with lubricants. The mold was cooled and finished by removing the overflows over the gate of the mold. The product was de-molded and subjected to quality inspection and package. 100 granules were prepared in total. Example 2 - Pentoxifylline suppository Pentoxifylline 50 g Semi-synthetic fatty acid glyceride 4500 g Glycerol 400 g Polysorbate-80 50 g Preparing process: Semi-synthetic fatty acid glyceride was added into a container, and heated in a water bath to melt. When the melt was cooled to about 50*C, glycerol and polysorbate-80 were added and evenly stirred. Pentoxifylline was then added and evenly stirred. The mixture was injected into a suppository mold coated with lubricants till slightly overflowed from the gate of the mold. The mold was cooled and finished by removing the solidified overflows over the gate of the mold. The product was de-molded and subjected to quality inspection and package. 100 granules were prepared in total. Example 3 - Pentoxifylline suppository 11 Pentoxifylline 50 g Polyethylene glycol 4000 2450 g Polyethylene glycol 1000 2450 g Glycerol 50 g Preparing process: Polyethylene glycol 4000 and polyethylene glycol 1000 were added into a container, and heated in a water bath allow to melt. When the melt was cooled to about 50*C, glycerol was added and stirred evenly. Pentoxifylline was then added and evenly stirred. The mixture was injected into a suppository mold coated with lubricants till slightly overflowed from the gate of the mold. The mold was cooled and finished by removing the solidified overflows over the gate of the mold. The product was de-molded and subjected to quality inspection and package. 100 granules were prepared in total. Example 4 - Pentoxifylline suppository Pentoxifylline 500 g Polyethylene glycol 4000 2250 g Polyethylene glycol 1000 2200 g Glycerol 50 g Preparing process: Polyethylene glycol 4000 and polyethylene glycol 1000 were added into a container, and heated in a water bath to melt. When the melt was cooled to about 50*C, glycerol was added and evenly stirred. Pentoxifylline was then added and evenly stirred. The mixture was injected into a suppository mold coated with lubricants till slightly overflowed from the gate of the mold. The mold was cooled and finished by removing the solidified overflows over the gate of the mold. The product was de-molded and subjected to quality inspection and package. 1000 granules were prepared in total. Example 5 - Pentoxifylline gel Pentoxifylline 10 g Carbomer 10 g Propylene glycol 60 ml Glycerol 50 ml Triethanolamine q.s. Purified water to 1000 g Preparing process: Carbomer was slowly added into -50% of the indicated amount of water under stirring 12 till a transparent gel matrix was formed. Pentoxifylline was dissolved in an appropriate amount of water, and then added into the matrix and stirred evenly. Propylene glycol, glycerol and the purified water were added to the indicated amount. Triethanolamine was added to neutral pH to obtain the final product. Example 6 - Pentoxifylline paste Pentoxifylline 20 g Glycerol monostearate 48 g Stearic acid 120 g White vaselin 100 g Triethanolamine 15 g Ethylparaben 3 g Sodium dodecyl sulfate 12 g Glycerol 18 g Purified water to 1000 g Preparing process: As an oil phase, glycerol monostearate, stearic acid, white vaselin and triethanolamine of the indicated amounts were heated to melt in a water bath, and then mixed. Pentoxifylline was dissolved in an appropriate amount of purified water. As a water phase, glycerol, sodium dodecyl sulfate, purified water and ethylparaben were mixed and heated to about 80*C. The pentoxifylline solution was added into the oil phase at 80'C under stirring while the temperature was kept at around 80*C. The homogeneous oil phase was slowly added into the water phase under slowly stirring. The mixture was then stirred under an increased rate. The paste was obtained after stopping stirring. Example 7 - Pentoxifylline ointment Pentoxifylline 10 g Glycerol monostearate 100 g Paraffin 100 g White vaselin 46 g Liquid paraffin 53 g Propylene glycol 50 g Span 80 5 g Ethyl p-hydroxybenzoate I g Purified water to 1000 g Preparing process: 13 Paraffin, glycerol monostearate, white vaselin, liquid paraffin, propylene glycol, Span 80 and ethyl- p-hydroxybenzoate were heated to melt in a water bath and kept at 80*C. Water at 80*C was slowly added thereto under stirring. The mixture was cooled and solidified to obtain an ointment base. Pentoxifylline was dissolved in an appropriate amount of purified water and then added to the base, to which water was added to 1000 g and mixed to obtain the ointment. Example 8 - Pentoxifylline spay Pentoxifylline 10 g Distilled water q.s. Glycerol 30 g Urea 2 g Benzalkonium bromide 0.1 g Sodium chloride 0.9 g Distilled water to 100 ml Preparing process: 10 g pentoxifylline was weighted at room temperature and atmospheric pressure, and then dissolved in an appropriate amount of distilled water. The other ingredients as indicated above, i.e. 30g glycerine, 2g urea, 0.lg benzalkonium bromide and 0.9 g sodium chloride were added. The distilled water was then added to 100 ml. The mixture was evenly mixed, canned, sealed, and subjected to quality inspection to obtain the final product. Example 9 - Pentoxifylline aerosol Pentoxifylline 10 g Distilled water q.s. Glycerol 5 g Urea 2 g Benzalkonium bromide 0.1 g Freon F 1 2 q.s. Distilled water to 100 ml Preparing process: 10 g pentoxifylline was weighted at room temperature and atmospheric pressure, and then dissolved in an appropriate amount of distilled water. The other ingredients as indicated above, i.e. 10 g glycerine, 2 g urea, 0.1 g benzalkonium bromide and an appropriate amount of propellant F 1 2 were added. The distilled water was then added to 100 ml. The mixture was evenly mixed, canned, sealed, and subjected to quality inspection to obtain the final product. 14 Example 10 - Conventional tablets of pentoxifylline Pentoxifylline 10 g Microcrystalline cellulose 200 g Sodium carboxymethyl starch 8 g Magnesium stearate 1.5 g 8% starch slurry q.s. Preparing process: Pentoxifylline was evenly mixed with the excipients of microcrystalline cellulose and sodium carboxymethyl starch. An appropriate amount of starch slurry was added to prepare a damp mass which was subjected to granulation with a 16 mesh sieve. The wet granules were dried at 60*C. The dry granules were finished with a 16 mesh sieve to separate fine power from the dry granules. The fine power was evenly mixed with magnesium stearate and mixed with the dry granules for tabletting to obtain 1000 tablets. The specification of the tablets was 10 mg/tablet. Example 11 - Conventional tablets of pentoxifylline Pentoxifylline 25 g Lactose 55 g Microcrystalline cellulose 15 g Sodium carboxymethyl cellulose 10 g Magnesium stearate 1.5 g 50% Ethanol q.s. Preparing process: Pentoxifylline, lactose and microcrystalline cellulose were screened with an 80 mesh sieve and then mixed evenly. A damp mass was prepared by adding 50% ethanol and then subjected to granulation with a 20 mesh sieve. The granules were blow-dried at 60C and finished with a 20 mesh sieve. The sodium carboxymethyl cellulose and magnesium stearate of the indicated amounts were added and mixed evenly for tabletting to obtain 1000 tablets. The specification of the tablets was 25 mg / tablet. Example 12 - Conventional tablets of pentoxifylline Pentoxifylline 80 g Microcrystalline cellulose 200 g Sodium carboxymethyl starch 8 g Zinc stearate 1.5 g 8% starch slurry q.s. 15 Preparing process: Pentoxifylline was evenly mixed with the excipients of microcrystalline cellulose and sodium carboxymethyl starch. An appropriate amount of starch slurry was added to prepare a damp mass, which was subjected to granulation with a 16 mesh sieve. The wet granules were dried at 60*C. The dry granules were finished with a 16 mesh sieve to separate fine power from the dry granules. The fine power was evenly mixed with zinc stearate and mixed with the dry granules for tabletting to obtain 1000 tablets. The specification of the tablets was 80 mg / tablet. Example 13 - Conventional tablets of pentoxifylline Pentoxifylline 50 g Mannitol 100 g Lactose 80 g Sodium carboxymethyl starch 8 g Magnesium stearate 1.5 g 8% starch slurry q.s. Preparing process: Pentoxifylline was evenly mixed with the excipients of mannitol, lactose and sodium carboxymethyl starch. An appropriate amount of starch slurry was added to prepare a damp mass which was subjected to granulation with a 16 mesh sieve. The wet granules were dried at 60*C. The dry granules were finished with a 16 mesh sieve to separate fine power from the dry granules. The fine power was evenly mixed with magnesium stearate and mixed with the dry granules for tabletting to obtain 1000 tablets. The specification of the tablets was 50 mg / tablet. Example 14 - Enteric-coated tablets of pentoxifylline Pentoxifylline 10 g Microcrystalline cellulose 200 g Sodium carboxymethyl starch 8 g Magnesium stearate 1.5 g 8% starch slurry q.s. Preparing process: Pentoxifylline was evenly mixed with the excipients of microcrystalline cellulose and sodium carboxymethyl starch. An appropriate amount of starch slurry was added to prepare a damp mass, which was subjected to granulation with a 16 mesh sieve. The wet granules were dried at 60*C. The dry granules were finished with a 16 mesh sieve to separate fine power from the dry granules. The fine power was evenly mixed with magnesium stearate and mixed 16 with the dry granules for tabletting. The tablets were coated with film-coating and enteric-coating solutions (the isolating layer accounting for 3% of the weight gain and the enteric coating accounting for 8% of the weight gain) so as to obtain 1000 tablets. The specification of the enteric-coated tablets was 10 mg / tablet. Example 15 - Enteric-coated tablet of pentoxifylline Pentoxifylline 25 g Lactose 55 g Microcrystalline cellulose 15 g Sodium carboxymethyl cellulose 10 g Magnesium stearate 1.5 g 50% ethanol q.s. Preparing process: Pentoxifylline, lactose and microcrystalline cellulose were screened with a 80 mesh sieve and then mixed evenly. A damp mass was prepared by adding 50% ethanol and then subjected to granulation with a 20 mesh sieve. The granules were blow-dried at 60'C and finished with a 20 mesh sieve. The sodium carboxymethyl cellulose and magnesium stearate of the indicated amounts were added and mixed evenly for tabletting. The tablets were coated with film-coating and enteric-coating solutions (the isolating layer accounting for 3% of the weight gain and the enteric coating accounting for 8% of the weight gain) so as to obtain 1000 tablets. The specification of the enteric-coated tablets was 25 mg / tablet. Example 16 - Enteric-coated tablet of pentoxifylline Pentoxifylline 50 g Microcrystalline cellulose 200 g Sodium carboxymethyl starch 8 g Zinc stearate 1.5 g 8% starch slurry q.s. Preparing process: Pentoxifylline was evenly mixed with the excipients of microcrystalline cellulose and sodium carboxymethyl starch. An appropriate amount of starch slurry was added to prepare a damp mass, which was subjected to granulation with a 16 mesh sieve. The wet granules were dried at 60*C. The dry granules were finished with a 16 mesh sieve to separate fine power from the dry granules. The fine power was evenly mixed with zinc stearate and mixed with the dry granules for tabletting. The tablets were coated with film-coating and enteric-coating solutions (the isolating layer accounting for 3% of the weight gain and the enteric coating accounting for 8% of the weight gain) so as to obtain 1000 tablets. The specification of the 17 enteric-coated tablets was 50 mg / tablet. Example 17 - Enteric-coated tablets of pentoxifylline Pentoxifylline 25 g Mannitol 100 g Lactose 80 g Sodium carboxymethyl starch 8 g Magnesium stearate 1.5 g 8% starch slurry q.s. Preparing process: Pentoxifylline was evenly mixed with the excipients of mannitol, lactose and sodium carboxymethyl starch. An appropriate amount of starch slurry was added to prepare a damp mass, which was subjected to granulation with a 16 mesh sieve. The wet granules were dried at 60*C. The dry granules were finished with a 16 mesh sieve to separate fine power from the dry granules. The fine power was evenly mixed with magnesium stearate and mixed with the dry granules for tabletting. The tablets were coated with film-coating and enteric-coating solutions (the isolating layer accounting for 3% of the weight gain and the enteric coating accounting for 8% of the weight gain) so as to obtain 1000 tablets. The specification of the enteric-coated tablets was 50 mg / tablet. Example 18 - Sustained-release tablets of pentoxifylline Pentoxifylline 100 g HPMC (K15M) 60 g Stearic acid Hog Microcrystalline cellulose 30 g 8% PVPk 0 70% ethanol in water 16 g (calculated by the amount of PVPko) Magnesium stearate 3 g Preparing process: The indicated raw materials and excipients were mixed evenly and screened with a 80 mesh sieve. The water solution of 8% PVPK 3 O 70% ethanol was used to prepare a damp mass, which was subjected to wet granulation with a 30 mesh sieve. The wet granules were dried at 50'C and then mixed with magnesium stearate for tabletting to obtain 1000 tablets. The specification of the sustained-release tablets was 100 mg /tablet. 18 Example 19 - Sustained-release tablets of pentoxifylline Pentoxifylline 80 g HPMC (K4M) 60 g Stearyl alcohol 120 g Lactose 40 g 8% PVPK3070% ethanol in water 16 mg (calculated by the amount of PVPK 3 O) Magnesium stearate 3 g Preparing process: The indicated raw materials and excipients were mixed evenly and screened with an 80 mesh sieve. The water solution of 8% PVPK30 70% ethanol was used to prepare a damp mass, which was subjected to wet granulation with a 30 mesh sieve. The wet granules were dried at 50*C and then mixed with magnesium stearate for tabletting to obtain 1000 tablets. The specification of the sustained-release tablets was 80 mg / tablet. Example 20 - Sustained-release tablet of pentoxifylline Pentoxifylline 75 g Sodium carboxymethyl cellulose 60 g Stearic acid 100 g Microcrystalline cellulose 30 g 8% PVPK3070% ethanol in water 16 g (calculated by the amount of PVPK 3 O) Magnesium stearate 2 g Preparing process: The indicated raw materials and excipients were mixed evenly and screened with an 80 mesh sieve. The water solution of 8% PVPK30 70% ethanol was used to prepare a damp mass, which was subjected to wet granulation with a 30 mesh sieve. The wet granules were dried at 50'C and then mixed with magnesium stearate for tabletting to obtain 1000 tablets. The specification of the sustained-release tablets was 75 mg / tablet. Example 21 - Pentoxifylline granules Pentoxifylline log Sodium carboxymethyl cellulose 60 g 8%PVPK 3 070% ethanol in water -16 g (calculated by the amount of PVPK3O) Sugar power 914 g 19 Preparing process: The granules were prepared according to the conventional process. Example 22 - Pentoxifylline granules Pentoxifylline 100 g Sodium carboxymethyl cellulose 160 g 8%PVPK 3 070% ethanol in water 16 g (calculated by the amount of PVPK3O) Sugar power 724 g Preparing process: The granules were prepared according to the conventional process. Example 23 - Pentoxifylline capsules Pentoxifylline log Sodium carboxymethyl cellulose 60 g 8%PVPK3070% ethanol in water 16 g (calculated by the amount of PVPK30) Sugar power 914 g Preparing process: The indicated raw materials were formulated by the conventional process and then filled into empty capsules. Example 24 - Pentoxifylline capsules Pentoxifylline 100 g Sodium carboxymethyl cellulose 160 g 8%PVPK 3 070% ethanol in water 16 g (calculated by the amount of PVPK 3 O) Sugar power 724 g Preparing process: The indicated raw materials were formulated by the conventional process and then filled into empty capsules. Comparative Example 1 - Theophylline tablets Theophylline 10 g Microcrystalline cellulose 200 g 20 Sodium carboxymethyl starch 8 g Magnesium stearate 1.5 g 8% starch slurry q.s. Preparing process: Theophylline was evenly mixed with the excipients of microcrystalline cellulose and sodium carboxymethyl starch. An appropriate amount of starch slurry was added to prepare a damp mass, which was subjected to granulation with a 16 mesh sieve. The wet granules were dried at 60*C. The dry granules were finished with a 16 mesh sieve to separate fine power from the dry granules. The fine power was evenly mixed with magnesium stearate and mixed with the dry granules for tabletting to obtain the final product. Comparative example 2 - Aminophylline tablets Aminophylline 10 g Microcrystalline cellulose 200 g Sodium carboxymethyl starch 8 g Magnesium stearate 1.5 g 8% starch slurry q.s. The preparing process was the same as Comparative Example I set forth above. Comparative example 3 - Caffeine tablets Caffeine log Microcrystalline cellulose 200g Sodium carboxymethyl starch 8g Magnesium stearate 1.5g 8% starch slurry q.s. The preparing process was the same as Comparative Example 1 set forth above. Comparative example 4 - Pargeverine tablets Pargeverine 10 g Microcrystalline cellulose 200 g Sodium carboxymethyl starch 8 g Magnesium stearate 1.5 g 8% starch slurry q.s. The preparing process was the same as Comparative Example 1 set forth above. 21 II. Pharmacodynamic Study on pentoxifylline Experimental Example 1: Effect of pentoxifylline on a mouse model of slow transit constipation 1. Objects Mice in test groups were subcutaneously injected with morphine to establish a mouse model of slow transit constipation. The stool weights evacuated by the mice were recorded. The colonic transit function of mice in the test groups was compared with that of the mice in the control group by the test of activated carbon gavage. The amounts of Cajal cells in colonic tissues of the two groups were compared by the immunohistochemical techniques. 2. Materials Animals: 80 ICR mice (SPF grade, specific pathogens free, half male and half female, weighed 20-25 g; Animal Center of New Time Medicine, Shandong); metabolic cages for mice (Fengshi Laboratory Animal Equipment Co., Ltd., Suzhou); injectable morphine hydrochloride (10 mg/vial; First Pharmaceutical Company, Shenyang); physiological saline; primary antibody (sc-168Santa Cruz Biotechnology, Inc., 200 mg/L); secondary antibody (goat anti-rabbit. antibody, Zhongshan Biotechnology Company); pentoxifylline tablets prepared in accordance with the same process as Example 10; pentoxifylline suppositories prepared in accordance with the same process as Example 3; theophylline tablets prepared in accordance with the same process as Comparative Example 1; aminophylline tablets prepared in accordance with the same process as Comparative Example 2; caffeine tablets prepared in accordance with the same process as Comparative Example 3; and pargeverine tablets prepared in accordance with the same process as Comparative Example 4. 3. Methods and Process 3.1 Establishment of the mouse model of slow transit constipation 80 ICR mice were randomly divided into 6 test groups, 1 normal control group and 1 model control group with 10 animals for each group. The six test groups were as follows: a pentoxifylline-tablet group, a pentoxifylline-suppository group, a theophylline-tablet group, an aminophylline-tablet group; a caffeine-tablet group; and a pargeverine-tablet group. All mice were housed in 80 metabolic cages in SPF environment. After 3 days of adaptive feeding, mice in the test groups and the model control group were injected subcutaneously with morphine hydrochloride at 2.5mg / (kg - d) and the normal control group was injected with physiological saline at the same dosage. The numbers of stool grains, dry weight of stools and body weight of the mice were recorded every 3 days, and the average daily weight (g) of stools was calculated. Reduction of the average daily weight of stools and the significant difference in the term of the average daily weight of stools in comparison with the normal control group were taken as the indicators of the successful establishment of the STC mouse 22 model. The injection was stopped upon the successful establishment. 3.2 Determination of the average daily weight of stools evacuated by mice After the successful modeling (from Day 46 of feeding), the mice were subjected to the following administrations: the mice in the pentoxifylline-tablet group were gavaged with pentoxifylline at a dosage of lmg/(kg-d) (calculated by pentoxifylline); the mice in the pentoxifylline-suppository group were rectally administered with the pentoxifylline suppositories at a dosage of lmg/(kg-d) (calculated by pentoxifylline); and the mice in the theophylline-tablet group, aminophylline-tablet group, caffeine-tablet group and pargeverine-tablet group were respectively gavaged with the corresponding agent at a dosage of Img/(kg-d). The mice in the normal control group and model control group were administered with distilled water. The numbers of stool grains, dry weight of stools and body weight of the mice were recorded every other day, and the average daily weight (g) of stools was calculated. The reduction of the average daily weight of stools compared with the normal control group indicated that the slow transit constipation was deteriorated. 3.3 Determination of the intestinal transit function The test of activated carbon gavage was used to determine the time of the first black feces excretion. The mice, after one week of drug withdrawal, were fasted for 24 hours and orally gavaged with 2 ml suspension comprising 100mg/ml activated carbon. The timing began by the end of the gavage to record the time from the completion of the gavage to the excretion of the first black feces. The longer time of the first black feces excretion suggests a higher severity of slow transit constipation. 3.4 Immunohistochemically staining of ICCs in mouse colon tissue and the comparison of the ICC amounts At the end of the experiments, mice were sacrificed by cervical dislocation, and the intestinal tracts from pylorus to rectum were taken by laparotomy. Two or three specimens of distal colon tissue were taken for each mouse, fixed in 4% formaldehyde solution, and then were subjected to paTaffin-embedding and serial sectioning (thickness: 4 pm to 5 tm). After de-waxing and hydration, the sections were placed into. EDTA buffer (pH 8.0), boiled for 15 min, incubated for 10 min, and then allowed to be cooled at room temperature. The sections were washed with PBS (pH 7.6) for three times, 5min for each time. 50 1 l of 3% hydrogen peroxide was added dropwisely on each section to block the activity of endogenous peroxidase. The sections were incubated at room temperature for 10min, washed with PBS solution (pH 7.6) for three times, 5min for each time. The serum was removed. 50 gl of the primary antibody (1:500) was added to each section. The sections were incubated at 37*C for 60min, and then washed with PBS for three times, 5min for each time. After the removal of PBS solution, 50gl of the biotin-labeled secondary antibody (1:50) was added. The sections were incubated at room temperature for 10min, and then washed with PBS solution for three times, 3 min for each time. After the removal of PBS solution, 5 0pl of streptavidin-peroxidase solution was added. The sections were incubated at room temperature for 1 0min, and then washed with PBS solution for three times, 3 min for each time. After the removal of PBS 23 solution, two drops of freshly prepared DAB were added and the sections were observed under a microscope for 3min to 10min. The sections were then rinsed with tap water and counterstained with hematoxylin, differentiated with 0.1% HCl in ethanol, and returned to blue by rinsing with running water, and dehydrated with gradient ethanol (and clarified with xylene) and mounted in neutral gum. The brown-stained cytoplasm indicated a positive reaction. Five high-power (x 200) visual fields were selected for each section. Lecia RX250 Image Analysis System and Qwin software were used to mark and calculate the area of c-kit positive cells. The smaller area of c-kit positive cells compared with the normal control group suggests a higher severity of slow transit constipation. 3.5 The statistic processing of experimental data The experimental data was input into SPSS 10.0 Statistical Software Package with t-test selected as the statistical method. The difference was considered as statistically significant at p <0.05. 4. Results The experimental results obtained above showed that: (1) Compared with the mice in the normal group, the mice in the model group showed extremely significant difference (p <0.01) in the terms of the average daily stool amounts, the time of first black feces excretion and the area of c-kit positive cells, indicating the successful establishment of the mouse model of slow transit constipation. (2) Compared with the mice in the model group, the mice in the pentoxifylline-tablet group and the pentoxifylline-suppository group showed significant difference in the terms of the average daily stool amounts, the time of first black feces excretion and the area of c-kit positive cells (p <0.05). However, the average daily stool amount, the time of first black feces excretion and the area of c-kit positive cells of the mice in the theophylline-tablet group, the aminophylline-tablet group, the caffeine-tablet group and the pargeverine-tablet group showed no significant difference (p >0.05). The results indicate that pentoxifylline can significantly improve the amount of stools evacuated by the mice, enhance intestinal propulsion of the mice and increase the number of intestinal ICC, alleviate the symptoms of slow transit constipation in the mice, while theophylline, aminophylline, caffeine and pargeverine do not have these effects. (3) Compared with the mice in the theophylline-tablet group, the aminophylline-tablet group, the caffeine-tablet group and the pargeverine-tablet group, the mice in the pentoxifylline-tablet group and the pentoxifylline-suppository group showed significant or even extremely significant difference regarding the average daily stool amount, the time of first black feces excretion and the area of c-kit positive cells. The results indicate that pentoxifylline is significantly superior over other non-selective phosphodiesterase inhibitions such as theophylline, aminophylline, caffeine and pargeverine with regard to the effects in the treatment of slow transit constipation. (4) Compared with the mice in the pentoxifylline-tablet group, the suppository group has 24 better efficiency regarding the average daily stool amount, the time of first black feces excretion and the area of c-kit positive cells, although there was no significant difference (p>0.05). The results indicate that the rectal administration of pentoxifylline is more potent than the oral administration of pentoxifylline in the treatment of slow transit constipation in mice. Table 1: Effects of pentoxifylline on mice with slow transit constipation Items Stool weight Time of the first Area of c-kit positive ICC (g/d) black feces (min) cells (10 4 im 2 ) Normal control group 11.02±3.24 157±58 112.6±9.8 Model control group 3.84±1.96" 380±80" 56.4±8.2"" Theophylline tablet 3.25±1.05 360±25 58.2±4.6 group Aminophylline tablet 2.98±1.28 332±56 60.4±5.8 group Caffeine tablet group 4.25±1.70 300±36 68.8±9.8 Pargeverine tablet 4.50±1.88 320±72 74.2±7.2 group Pentoxifylline tablet 7

.

62

±

2

.

48 **"a" 195±70***$& 92.2±10.5*"'$&&66 group Pentoxifylline 9

.

8 0± 2

.

6 2 **#&A 170± 6 4 **S&A 98.0±11.2**##$$&&AA suppository group * p<0.05, in comparison with the model control group; p<0.01, in comparison with the model control group; p<0.01, in comparison with the normal control group; " p<0.05, in comparison with the pentoxifylline tablet group; # p<0.05, in comparison with the theophylline tablet group; p<0.01, in comparison with the theophylline tablet group; $ p<0.05, in comparison with the aminophylline tablet group; $$ p<0.01, in comparison with the aminophylline tablet group; & p<0.05, in comparison with the caffeine tablet group; && p<0.01, in comparison with the caffeine-tablet group; p<. , in comparison with the pargeverine-tablet group; ^ p<0.01, in comparison with the pargeverine-tablet group. 5. Discussion Patients with STC have decreased amounts of the interstitial cells of Cajal (ICC) with reduced sizes. The decrease of ICC is thus considered as the main intestinal histocytological character of STC. As a proto-oncogene, c-kit locates on the W locus of Chromosome 5, and codes for a kit receptor, which belongs to tyrosine kinase membrane receptors. The expression of c-kit in ICC is closely related with intestinal motility. The ICC can be identified with anti-c-kit antibodies. In the present invention, the numbers of positive ICC in the mice of each group were compared in pairs by labeling ICC with anti-c-kit antibody. After administration, 25 the mice in the model control group had decreased stools, reduced intestinal propulsion, and decreased ICCs in intestinal tract, which were significantly different from those of the normal group. Hence, the model established by the present invention has the same physiological and histocytological characters as slow transit constipation. The pentoxifylline groups, including pentoxifylline tablet group and pentoxifylline suppository group, show unexpected effects on the improvement of the above symptoms, i.e. the increase of the average daily stool amount, the improvement of the intestinal propulsion and the increase of the amount of intestinal ICC. Experimental Example 2 - Effects of pentoxifylline on anal sphincter of rats 1. Materials and methods 1.1 Materials 70 Wister rats (six, male, weighted 240 ± 10g; Animal Center of New Time Medicine, Shandong) were housed in stainless steel cages at 24 ± 0.5*C, relative humidity of 55 ± 10% with 12 hours of light each day from 7:00 to 19:00. The rats were fed with standard diets/water ab libitum. Theophylline tablets prepared in accordance with the same process as Comparative Example 1; aminophylline tablets prepared in accordance with the same process as Comparative Example 2; caffeine tablets prepared in accordance with the same process as Comparative Example 3; pargeverine tablets prepared in accordance with the comparative examples; 0.9% NaCl solution; pentoxifylline tablets prepared in accordance with the same process as Example 10; and pentoxifylline aerosols prepared in accordance with the same process as Example 9. 1.2 Methods All rats were randomly divided into 7 groups with 10 animals each group. The groups and the administration were set forth as follows: Pentoxifylline-gavage group: pentoxifylline was administered by gavage at 0.1 5mg/kg-d; Pentoxifylline-topical-administration group: pentoxifylline was topically administered at 0.15mg/kg-d; Physiological saline group: physiological saline was administered by gavage at 0. 15mg/kg-d; Theophylline group: theophylline was administered by gavage at 0.15mg/kg - d; Aminophylline group: aminophylline was administered by gavage at 0.15mg/kg - d; Caffeine group: caffeine was administered by gavage at 0.15mg/kg - d; and Pargeverine group: pargeverine was administered by gavage at 0.15mg/kg - d. The anal sphincter electromyograms and anorectal pressure of the animals in the above seven groups were determined at one hour prior to administration and 72 h after administration. Counterpoint MK II Electromyography (manufactured by DANTEC company; filter band of 500-1000Hz; sensitivity 0.2-lmV/cm; scanning speed 0.5-Ims) was used for determining the anal sphincter electromyograms by placing the surface electrodes on the skin around the anus. The anal sphincter electromyograms of the mice from four test groups were recorded. The mean amplitude of the potentials and the average duration time were calculated 26 with the software coming with the device. RT-2070 Multi-channel Anorectal Pressure Meter plus a self-made micro-balloon (maximum of 0.5ml) manometric catheter were used to determine the anorectal pressure of the animals. A mini-sized multi-pole probe was probed into the anorectum to a depth of 0.5 cm to measure the anorectal resting pressure, maximum autonomic systolic pressure of anorectum and the value of rectoanal inhibitory reflex. The anorectal pressure was measured only with a single-aerocyst in consideration of the short and narrow anal canal of rats and unapparent boundary between anus and rectum. The measured values were recorded with a polygraph at the same time. After the above measurement, the rats were sacrificed. The anal sphincter tissues of the rats from four test groups were cut off. These tissues were subjected to pathological sections and hematoxylin-eosin (HE) staining. The histomorphological characters of the muscle fibers in the anal sphincter of the rats were observed with a 400X optical microscope. 1.3 Statistical analysis All statistical data was expressed as means ± variance. SPSS10.0 statistical analysis software was used for the analysis of variance. The difference was considered as statistically significant at P <0.05. 2 Results 2.1 Changes in the anal sphincter electromyograms The experimental results showed that the anal sphincter electromyograms of rats from all of the seven groups had regular and continuing electrical activities before and after the treatments. The anal sphincter electromyograms of the animals from all of the seven groups had no statistical significance before the treatments (P <0.05) with the potential amplitude of (96.8 ± 35.7) pV and the potential duration of (3.8 ± 0.9) ms. Compared with the physiological-saline group, the electromyograms of all the treatment groups had decreased action potential amplitude and prolonged duration time after 72 h of the treatments. However, the theophylline group, aminophylline group, caffeine group, pargeverine group had no significant difference from the physiological-saline group, while the pentoxifylline-gavage group and topical administration group had significant difference from the physiological-saline group. Compared with the theophylline group, aminophylline group, caffeine group, pargeverine group, the pentoxifylline-gavage group and topical administration group had significant difference in terms of the decrease of potential amplitudes. Compared with the theophylline group and pargeverine group, the pentoxifylline-gavage group and topical administration group had significant difference in terms of the extension of the duration time. See Table 2 for the details. 27 Table 2: Potential amplitudes and mean duration time of anal sphincter electromyograms Groups potential amplitude (pV) mean duration time (ms) Physiological saline group 98±32 3.8±0.9 Theophylline group 85±28 3.7±0.8 Aminophylline group 82±26 4.0±1.1 Caffeine group 80±30 4.2±0.6 Pargeverine group 86±32 3.9±0.4 Pentoxifylline-gavage group 62

±

26 ''*0$ 4.8±0.6'" Pentoxifylline-topical 58±29* 5.0± 1.0*' administration group Note: * p<0.05,. in comparison with physiological-saline group; # p<0.05 in comparison with the theophylline group; S p<0.05 in comparison with the aminophylline group; & p<0.05 in comparison with the caffeine group; and A p<0.05 in comparison with the pargeverine group. 2.2 Anorectal pressure At 72 hours after the treatments, the anorectal resting pressure, maximum anorectal autonomic systolic pressure and the balloon volume representing the rectoanal inhibitory reflex of all treatment groups were lower than those of the physiological saline group. The theophylline group, aminophylline group, caffeine group, pargeverine group had no significant difference from the physiological saline group, while the pentoxifylline-gavage group and topical administration group exhibited significant difference in comparison with the physiological saline group. In comparison with the theophylline group, aminophylline group, caffeine group, pargeverine group, the pentoxifylline-gavage group and topical administration group showed significant differences in terms of the decreases of the anorectal resting pressure, maximum anorectal autonomic systolic pressure and the balloon volume representing the rectoanal inhibitory reflex value. In comparison with the pentoxifylline-gavage group, the pentoxifylline topical administration group had better efficiency on the decreases of the anorectal resting pressure, maximum anorectal autonomic systolic pressure and the balloon volume representing the rectoanal inhibitory reflex value, though the difference between the two groups had no statistical significance. See Table 4 for the details. For outlet obstruction constipation which accounts for more than 50% of the functional constipations, sustained cramp and increased pressure of internal and external anal sphincter are of the main pathophysiological changes. The anorectal resting pressure, maximum autonomic systolic pressure and the value of rectoanal inhibitory reflex in the groups treated with pentoxifylline were significantly decreased, demonstrating that the muscle tone of the anal sphincter was effectively reduced and the effect of relaxing anal sphincter was achieved. The observation of histopathological sections showed that anal sphincter fibers of mice in the 28 pentoxifylline-treated groups atrophied to a certain extent. The experiments showed that pentoxifylline can effectively reduce the pressure of anal sphincter. It provides a novel method and approach for the clinical treatment of chronic outlet obstruction constipation, and thus is worthy of further study. Table 3: Effects of pentoxifylline on anorectal pressure Groups- Resting Maximum autonomic Value of Inhibitory pressure systolic pressure reflex /ml /mmHg /mmHg Physiological saline group 7.4±1.7 22.9±4.7 0.39±0.08 Theophylline group 6.5±1.5 18.2±5.4 0.32±0.10 Aminophylline group 6.3±1.2 16.4±6.0 0.34±0.07 Caffeine group 6;2±1.7 18.0±3.5 0.28±0.04 Pargeverine group 7.0±1.8 20.0±7.2 0.36±0.03 Pentoxifllin-gavage 3.5±0.8'' 12.6±2.4'"""' 0.1 6±0.04'': administration group Pentoxifylline topical 3.2± 1.0*'s 11.2±2.4*'&'* 0. 12±0.02"A'3 administration group Notes: * p<0.05, in comparison with physiological saline group; p<0.05, in comparison with the theophylline group; S p<0.05, in comparison with the aminophylline group; & p<0.05, in comparison with the caffeine group; and Ap<0.05, in comparison with the pargeverine group. Experimental Example 3: Effects of pentoxifylline on mucus from rectal mucosa of rats with loperamide-induced constipation 1. Experimental materials SD rats (8-week-old, weighted 240 ± 10g; Animal Center of New Time Medicine, Shandong) were housed in stainless steel cages at 24 ± 0.5*C, relative humidity of 55 ± 10% with 12 hours of light each day from 7:00 to 19:00. The rats were fed with standard diets/water ab libitum. 2. Experimental methods and procedures The rats were randomly divided into a pentoxifylline-gavage group, a pentoxifylline topical-administration group, a model control group and a normal control group, with five animals each group. The rats were subjected to adaptive feeding for three days. The pentoxifylline-gavage group, the pentoxifylline topical-administration group and the model control group were administered with 1.5mg/kg loperamide (pre-dissolved in 0.9% NaCl solution before use) via subcutaneous injection twice each day at 09:00'and 18:00. The rats in the normal group were treated in accordance with the same experimental methods for the model groups, excepting injected with 0.9% NaCl solution. 29 The rats in the pentoxifylline-gavage group were gavaged with pentoxifylline tablets at a dosage of 1.5mg/kg at 10:00 each day. The rats in the topical-administration group were rectally administered with pentoxifylline suppositories at a dosage of 1.5mg/kg. Said dosages were based on the amount of pentoxifylline. The rats in the model control group and the normal control group were administered with distilled water by the same procedure at the same dosage as described above. The rats in each of above groups were housed in cages with feeds ab libitum. After 14 days of the administration, the rats were subjected to ketamine anesthesia and laparotomy. The distal colon (8cm in length) was excised, split open longitudinally, washed to remove the contents, and then fixed with 10% neutral formalin for later use. The fixed specimens were all embedded in paraffin, sectioned by conventional methods and stained by AB-PAS method. The cells comprising mucus had lower gray values, while the cells comprising no mucus had higher gray values. IMS True-Color Image Analysis System (Shinetech Info Technology Co., Ltd., Shanghai) was used to analyze the mucus-positive area. The technical parameters were set as follows: an image resolution of 512 x 512 and a gray level of 256. The microscope was Olympus-BH2. For each specimen, six visual fields at a low magnification of 10 x 10 were detected randomly. The experimental results were expressed by means ± SD. The variance analysis was carried out by SPSS 10.0 software package. 3 Results The experimental results showed that: (1) The intestinal mucosal epithelium of the rats in the normal control group was rich in mucus. In contrast, the mucus in the intestinal mucosal epithelium of the rats in the model control group significantly decreased, showing statistical difference from the normal group (p <0.01). (2) Compared with the rats in the model group, the mucus in the intestinal mucosal epithelium of the rats in the pentoxifylline-gavage group and the topical administration group significantly increased with statistical differences. (3) Compared with the pentoxifylline-gavage group, the mucus in the intestinal mucosal epithelium of the rats in the topical administration group significantly increased with statistical differences (p<0.05), indicating that the direct administration via rectal mucosa is more effective on the enhancement of the intestinal mucosal function. By the administration of pentoxifylline, the inventor surprisingly finds that pentoxifylline has unexpected effects on the improvement of colon function and the enhancement of the normal mucus secretion by intestinal mucosa. It can been seen that in the treatment of functional constipation, pentoxifylline improves not only the symptoms of functional constipation but also the secretion of intestinal mucosal mucus and the function of intestinal mucosa, and thus fundamentally achieves the significant alleviation of functional constipation. 30 Table 4: Effects of pentoxifylline on mucus in rectal mucosa of rats with loperamide-induced constipation Groups numbers Area of mucus (pm 2 ) Normal control group 10 6200.2±939.2 Model control group 10 1752.8±170.0"" Gavage group 10 3979.6±199.4** Topical administration group 10 4580.4±246.2*** p<0.01, in comparison with the model control group; Dp<0.05, in comparison with the gavage group; and "" p<0.01, in comparison with the normal control group. Experimental Example 4: Investigation of therapeutic effects of pentoxifylline on volunteers with functional constipation 1. Clinical information 1.1 Diagnostic criteria In reference to the diagnostic criteria for the chronic functional constipation introduced in the worldwide meeting of functional gastrointestinal disorders in Rome in 1999 (Rome II criteria), it has two or more of the following symptoms for at least 12 weeks, which need not be consecutive, in the preceding 12 months: (1) straining in one-fourth of defecations; (2) lumpy or hard stools in one-fourth of defecations; (3) sensation of incomplete evacuation in one-fourth of defecations; (4) sensation of obstruction/blockage of the anus in one-fourth of defecations; (5) use of manual maneuvers to facilitate in one-fourth of defecations (pelvic floor dysfunctional diseases), and (6) less than three defecations per week; no loose stools; and inconformity with the diagnostic criteria for irritable bowel syndrome. Moreover, the patients who are suffered from the constipation caused by the intestinal or systematical organic factors as well as drug factors should be excluded. According to blockage sites and motility dysfunction, functional constipation can be generally divided into three types as slow transit constipation (STC), outlet obstructive constipation (OOC), and mixed constipation (MIX). 1.2 Normal information 240 clinical volunteers, aging from 18 to 65 were involved in the investigation, including 96 males and 144 females, with the disease course of 1 to 6 years. These volunteers had signed the informed consent form, and were diagnosed as functional constipation, including 105 cases of slow transit constipation (43.75%), 50 cases of outlet obstruction constipation (20.83%) and 85 case of mixed constipation (35.42%). 2. Treatment 2.1 Groups According to the content specifications of the tablets administered, the volunteers were divided into 10 treatment groups with 24 volunteers each group. The volunteers received a 31 7-day treatment as follows: Conventional tablet (10mg) group: conventional oral tablets (10 mg/tablet, prepared by the same process as Example 10), one tablet each time, three times each day; Conventional tablets (50mg) group: conventional oral tablets (50 mg/tablet, prepared by the same process as Example 13), one tablet each time, three times each day; Conventional tablets (80mg) group: conventional oral tablets (80 mg/tablet, prepared by the same process as Example 12), one tablet each time, three times each day; Sustained-release tablets (75mg) group: sustained-release oral tablets (75 mg/tablet, prepared by the same process as Example 20), one tablet each time, once per day; Sustained-release tablets (100 mg) group: sustained-release oral tablets (100 mg/tablet, prepared by the same process as Example 18), one tablet each time, once per day; Enteric-coated tablets (25 mg) group: enteric-coated oral tablets (25 mg/tablet, prepared by the same process as Example 15), one tablet each time, three times each day; Enteric-coated tablets (50 mg) group, enteric-coated oral tablets (50 mg/tablet, prepared by the same process as Example 16), one tablet each time, three times each day; Sustained release tablets (400 mg) group, sustained-release oral tablets (400mg/tablet, prepared by the same process as Example 18), one tablet each time, once per day; Enteric-coated tablets (120 mg) group, enteric-coated oral tablets (100 mg/tablet, prepared by the same process as Example 16), one tablet each time, three times each day; and Conventional tablets (100 mg) group, conventional oral tablets (100mg/tablet, prepared by the same process as Example 10), one tablet each time, one time each day. 2.2 Indexes for Observation (1) Defecation intervals, the texture of stools and the degree of straining; (2) Stool Routine; (3) Barium Enema; (4) Fiber Colonoscopy; (5) Adverse effects after administration, including the conditions of nausea, indigestion, flatulence, dizziness, or headache. The adverse effects and the total case having adverse effects were recorded. Among the above indexes, (1) and (2) are necessary ones, while (3) and (4) are optional ones. 3. Criteria for therapeutic effects and results 3.1 Criteria for therapeutic effects on the disease Cured: stools return to normal or premorbid level, and other symptoms are disappeared; Markedly effective: constipation is obviously alleviated; time intervals and the quality of stools become close to the normal state; or stools are slightly dry, defecation interval is within 72 h; and most of the other symptoms are disappeared; Effective: the defecation intervals are reduced by one day, or lumpy stools are improved and other symptoms are alleviated; and Ineffective: none of the constipation and other symptoms is alleviated. 3.2 Data processing Data was processed as follows: Effective rate = (cases being clinically cured + cases showing markedly effective 32 effects+ cases showing effective effects) / total cases in the treatment group x 100%; and Rate of adverse reactions = cases having adverse reactions / total cases in the treatment groupx100%. 3.3 Results The results from clinical treatments showed that, the symptoms of volunteers with functional constipation were significantly alleviated in the conventional tablet groups (10mg, 50mg and 80mg), sustained-release tablet groups (75mg and 100mg) as well as the enteric-coated tablet groups (10 mg and 50 mg). The effective rates were 58.33% to 87.50%, and the average total effective rate was 77.38%. The incidences of adverse reactions were low (0% to 8.33%), and the average incidence of adverse reactions was 2.08%. In contrast, the effective rates of sustained release tablet group of 400mg and the enteric-coated tablet group of 120mg were 41.67% to 50.00%, and the average effective rate was 45.83%; the incidences of adverse reactions were relative higher (12.50% to 33.3%) and the average incidence of adverse reactions was 22.92%; and there were cases with symptoms of functional constipation deteriorated. It can be seen that compared with the groups of tablets comprising higher dosages of pentoxifylline, the groups of the tablets comprising lower dosages (10mg to 100mg) of pentoxifylline have higher effective rates and lower incidences of adverse reactions in the treatment of functional constipation with statistical differences. The tablets comprising lower dosage (10mg to 100mg) of pentoxifylline according to the present invention can be used as a medicament for treating functional constipation. Results are shown in Table 5. Table 5: observations of therapeutic effects of pentoxifylline tablets on clinical volunteers with functional constipation Treatment groups cases Effective rate Incidence of adverse notes (%) reactions /% Conventional tablet, 10mg 24 58.33 0AA_ Conventional tablet, 50mg 24 83.33 A* 0 _____ Conventional tablet, 80mg 24 75.00 ' 4.17 A* Sustained-release tablet, 75mg 24 87.50A' 0 AA Sustained-release tablet, 80mg 24 83.33 A' 4.17 As Enteric-coated tablet, 10mg 24 66.67'' 0 A A.. Enteric-coated tablet, 50mg 24 8 7

.

5 0 ' 0 A A Conventional tablet, 100mg 24 62.50A' 8.33 Enteric-coated tablet, 120mg 24 41.67 12.50 Deteriorated I_ constipation, I case Sustained-release tablet, 400mg 24 50.00 33.33 Deteriorated constipation, 2 cases A p<0.05, in comparison with the enteric-coated tablets (120 mg) group; * p<0.05, in comparison with the sustained release tablets (400 mg) group; A A p<0.01, in comparison with the enteric-coated tablets (120 mg) group; 33 p<0.01, in comparison with the sustained release tablets (400 mg) group. The skilled person in the art could envisage that the granules or capsules of the pharmaceutical composition comprising 10 mg to 100 mg of pentoxifylline can achieve the same or similar effects as the tablets of the pharmaceutical composition comprising 10 mg to 100 mg of pentoxifylline. This further demonstrates that the pharmaceutical compositions comprising 10 mg to 100 mg of pentoxifylline can be used as a medicament for treating functional constipation. The present invention has been described in connection with specific preferred embodiments. Various equivalent variations of the present invention will be apparent to those skilled in the art and all fall into the scope of the present invention. The preferred embodiments within the scope of the present invention will be considered as a result of the motivation given by the present invention and are included in the present invention. The equivalent variations are not limited to the follows: 1. Any experiments carried out in accordance with Experiments Examples 1-4 of the present invention with any of the oral preparations or the topical preparations for external use provided by the present invention, or administration of any of the preparations of the pharmaceutical compositions provided by the present invention, including oral preparations and topical preparations for external uses, to any animal models of functional constipation reported by article documents. 2. The experiments performed with pentoxifylline at the dosages calculated according to the surface area or the weight based on the dosages disclosed in the present invention for the treatment of functional constipation are deemed as motivated by the present invention. 34

Claims (12)

1. Use of pentoxifylline in the preparation of a medicament for preventing or treating functional constipation.

2. Use of claim 1, wherein the medicament is a pharmaceutical composition comprising pentoxifylline.

3. Use of claim 2, wherein the pharmaceutical composition is a topical preparation.

4. Use of claim 3, wherein pentoxifylline is present in an amount of 0.1%-10% by weight based on the topical preparation.

5. Use of claim 3 or 4, wherein the topical preparation is spray, aerosol, suppository, gel, pasty, cream, ointment, solution, emulsion or liposome preparation.

6. Use of claim 2, wherein the pharmaceutical composition is an oral preparation.

7. Use of claim 6, wherein the pharmaceutical composition is in the form of tablets, capsules, dropping pills, granules, powder or oral solutions.

8. Use of claim 6 or 7, wherein the pharmaceutical composition comprises 10 mg to 100mg of pentoxifylline.

9. Use of claim 6 or 7, wherein the tablet is a conventional tablet, an enteric-coated tablet or a sustained-release tablet.

10. Use of claim 9, wherein pentoxifylline in one conventional tablet is in an amount of 10 mg, 25 mg, 50 mg or 75 mg; pentoxifylline in one enteric-coated tablet is in an amount of 25 mg or 50 mg; or pentoxifylline in one sustained-release tablet is in an amount of 75 mg or 80 mg.

11. A method for treating functional constipation, comprising the step of administering a therapeutically effective amount of a pharmaceutical composition comprising pentoxifylline to a patient.

12. The method of claim 11, wherein the pharmaceutical composition is the pharmaceutical composition of any one of claims 2-10. 35