Method for treating anal fissure cases

FIELD: medicine.

SUBSTANCE: method involves carrying out histological study of smear imprint, bioptate or operation preparation. Histological picture corresponding to the first stage of wound process, conservative therapy course is to be complemented with peroral introduction of Pinaverium bromide at a dose of 50 mg thrice a day 10 days long and local transanal instillations 2 ml 0.1% glycerol trinitrate solution twice a day 6 weeks long. Conservative therapy course at the second stage of wound process is to be complemented with Mebeverine hydrochloride at a peroral dose of 200 mg thrice a day 2 weeks long and intramuscular introduction of Dalargin at a dose of 1 mg twice a day 2 weeks long. Conservative therapy course at the third stage of wound process is to be complemented with Mebeverine hydrochloride at a peroral dose of 200 mg twice a day 2 weeks long and intramuscular introduction of Dalargin at a dose of 2 mg twice a day 2 weeks long and local transanal instillations with 2 ml 0.1% glycerol trinitrate solution twice a day 4 weeks long. Conservative therapy course at the second and the third stage of wound process is also to be complemented with peroral introduction of nonsteroid anti-inflammatory means.

EFFECT: enhanced effectiveness of treatment when applied as rational drug the in postoperative period; accelerated rehabilitation; reduced frequency of disease recurrence.

 

The invention relates to medicine, namely to colorectal surgery, and can be used for the treatment of patients with anal fissure.

The incidence of anal fissure, according to the uptake is 20-23 cases per 1000 of the adult population, suffer more often from women young and middle age [Vorobyev GI Basics of Coloproctology. - Rostov-on-don: Phoenix, 2001, 414 S.], more than one third of patients are of working age [Babaev OG, countries O.K., Hojanepesov K. Treatment of anal fissures using laser photocoagulation. - Surgery. - 1990. No. 6. - P.21-24]. According to V.D. Fedorov et al. a sharp crack has a smooth straight edge, the bottom of her presents muscle tissue of the anal sphincter. Over time, the bottom edge cracks are covered by granulation tissue with fibrinous plaque. In the future, which is characteristic of chronic cracks on the edges is the growth of connective tissue and the tissues surrounding it, develop inflammatory and trophic changes [Fedorov V.D. et al. Clinical surgical proctology. - Moscow, GNCC, 1994, 432 S.]. When microscopy is determined by the defect multilayered epithelium with its thickening in the region of the edges of the "ulcer". The bottom of the ulcer usually presents Mature granulation or sclerotioides connective tissue. Sometimes the scar in the area of the bottom crack of the soap is being circulated at a depth of 2-5 mm, with the inclusion of small nerves and muscle bundles [GI sparrows Fundamentals of Coloproctology. - Rostov-on-don: Phoenix, 2001, 414 S.]. Next GI Vorobyev et al. indicate that in some cases the inflammation is weak, but other observations inflammation considerably, and is sometimes accompanied by the emergence of a fistulous course. Non-healing wound in the anal canal poorly resists virulent infection of the contents of the rectum, and may be local or distributed in adrectal tissue inflammation [Rivkin V.L., Bronstein A.S., fine S., EN VK Guide of Coloproctology. - M.: publishing house Medpraktika-M, 2004, 488 S.].

When applying any wounds (including, after the onset of anal fissure) is developing a so-called wound process. The wound healing process is a complex series of local and systemic biological reactions of the organism that develops in response to tissue damage, introduction of infection and focused on their healing [Datsenko BM, Lyapunov N.A., Mohart N.A., etc. theory and practice of local treatment of purulent wounds. - Kiev: Health, 1995, 190 S.; Datsenko BM, Druzhinin E.B., Protsenko A.G. Hemorrhoids: principles of treatment, diagnosis. - Kharkiv medical journal. - 1995. - №3-4. - S.43-46]. During his have the destructive and regenerative changes of the tissues forming the wound and adjacent to it, connective, epithelial, nerve, muscle [Wounds and wound infection: a guide for physicians Ed. M.I. Cousin and BM Kostjuchenko). - 2nd ed., revised and enlarged extra - M.: Medicine, 1990, 592 S.: ill.].

From the position of General pathology of the wound healing process is a special case of inflammation, manifested by a combination of local destructive and inflammatory changes, and General reactions [Davydov IV Pathological anatomy and pathogenesis of human diseases: Guide for physicians, vol. 1 (Ed. by A. I. Abrikosov). - M.: Medgiz, 1956, 574 S.].

According to M.I. Cousin et al. (1990) the course of the wound process is conventionally divided into 3 main phases. In phase 1 along with goes exudation and absorption (resorption) of toxins, bacteria and products of tissue destruction. The suction from the wound goes before closing the wound by granulation. With extensive purulent wounds resorption of toxins leads to intoxication, there resorptive fever. phase 2 - phase regeneration is the formation of granulations, meaning "gentle" connective tissue with newly formed capillaries. 3 phase - to-phase organization of the scar and epithelization in which "soft" connective tissue is transformed into a dense scar, and epithelialization begins with wound edges [of Wounds and wound infection: a guide for physicians (Ed. by M.I. Cousin and BM Kostjuchenko). - 2nd ed., revised and enlarged extra - M.: Medicine, 1990, 592 S.: ill.].

It is known that an acute anal fissure lasts 3-4 weeks, subacute - 3-4 months the CA, chronic - after 4-6 months with no tendency to heal in the conservative treatment [Zhukov B.N., Shabaev V.M., Isaev V.R., Lysov N.A. Coloproctology. Samara, Samara state medical University, 1999, 132 S.].

The main reason for the formation of chronic anal fissure is hypertonicity of the internal anal sphincter and associated pain [Corman M.L. Colon and rectum surgery. - Philadelphia: J.B. Lippincott Company, 2003, 784 p.; J.N. Lund Nitric oxide deficiency = MKD in the internal anal sphincter of patients with chronic anal fissure. - Int Journal Of Colorectal Dis. 2005, Jul 29; Muthukumarassamy R., Robinson SS, Sarath S.C., Raveendran R. Treatment of anal fissures using a combination of minoxidil and lignocaine: a randomized, double-blind trial. - Indian Journal Gastroenterol. 2005, Vol.24, No. 4, p.158-60]. V.D. Fedorov et al., States that in inflammatory and trophic changes involved nerve endings on the bottom of the crack, contributing to the emergence of unhealed ulcers. When this occurs spasm of the sphincter of the anus and develops a vicious circle, typical of chronic disease [Fedorov V.D. et al. Clinical surgical proctology. - Moscow, GNCC, 1994, 432 S.].

Treatment strategy depends on the stage of the disease. In acute and subacute fracture designate the complex of conservative measures aimed at the elimination of pain and sphincteroplasty, treatment of chronic fissure, as a rule, surgical [Zhukov B.N., Shabaev V.M., Isaev V.R., Lysov N.A. Coloproctology. Samara, Samara state medical University, 1999, 132 S.]. Removing the b is there not an end in itself, but the principle of treatment: decreases the degree of spasm of the sphincter muscles and there is hope to heal the wound in the wall of the anal canal [Rivkin V.L., Bronstein A.S., fine S., EN VK Guide of Coloproctology. - M.: publishing house Medpraktika-M, 2004, 488 S.]. Despite the existence of many conservative and surgical methods of treatment, the recurrence rate and complications remains high.

It is known that to begin treatment of acute anal fissure, especially emerged first, followed with conservative measures [Rivkin V.L., Bronstein A.S., fine S., EN VK Guide of Coloproctology. - M.: publishing house Medpraktika-M, 2004, 488 S.]. The presence of spasm of the sphincter on the background of scar fissures, hemorrhoids or chronic paraproctitis require surgical treatment [Koplatadze A.M., Bondarev Y.A. Treatment of acute anal fissures. Journal of surgery named. I.I. Grekov. - 1990. Volume 144, No. 1. - S-112].

The main problem of operations for anal fissures is to decide whether to do additional sphincterotomy, and if you want, in what way. Without this additional manipulation in most cases the operation is success does not, there is a recurrence of cracks due to the recurring tonic contractions of the sphincter [Vorobyev GI Basics of Coloproctology. - Rostov-on-don: Phoenix, 2001, 414 S.].

If anal fissure spasm is not defined or expressed nathnac the tion, shows the excision of cracks within a healthy mucous membrane, in patients with severe spasm - shown side submucosal sphincterotomy [Vorobyev GI Basics of Coloproctology. - Rostov-on-don: Phoenix, 2001, 414 S.]. However, J. Pitt et al. note that sphincterotomy required more than half of patients with chronic crack, and when the sharp crack of an effective conservative therapy [Pitt J., Dawas K., Dawson P. Dissapointing results of glyceril trinitrate ointment in the treatment of chronic anal fissures. - Diseases Colon Rectum. - 1999, Vol.42, No. 4, p.A12].

However, after a closed lateral subcutaneous sphincterotomy risk of postoperative anal incontinence can reach 10.2-35% [Khubchandani I.T., Reedand J.F. Sequelae of internal sphincterotomy for chronic fissure in ano. - British Journal Surgery. - 1989. - Vol.76. - P.431-434; Rotholtz N.A., Bun M., Mauri, M.V., Bosio R., Peczan C.E., Mezzadri N.A. - Long-term assessment of fecal incontinence after lateral internal sphincterotomy. - Coloproctology. - 2005. - Vol.9 (2). - P.115-118], and therefore its supporters suggested to change the depth and location of the incision, reduce time tamponade anal canal [Fedorov V.D., sparrows GI, Rivkin V.L. Clinical surgical proctology. - M.: SSC of Coloproctology, 1994, 432 S.].

The risk of anal incontinence after surgical treatment of anal fissure increase excessive (more than 50% of the height) dissection of the internal sphincter, the original existing dysfunction of the pelvic floor on the background of multiple births, long-beings is affected constipation and elderly patients. Research results Y.A. Him et al. [Shelygin Y.A., Zharkov E.E., Orlova, L.P., Podmarenkova L. F., Flights NN. Long-term results of excision of anal fissure in combination with a lateral subcutaneous sphincterotomy. - Surgery. - 2005. No. 7. - Pp.33-39] allow us to conclude that it is necessary to make a careful examination of patients before surgery, including functional investigation of the locking apparatus of the rectum.

In addition, the spread method "chemical" or "pharmacological" sphincterotomy, based on local application of glycerol trinitrate and isosorbide dinitrate [Utzig M.J., Kroesen AJ, H.J. Buhr Concepts in pathogenesis and treatment of chronic anal fissure - a review of the literature. - American Journal Gastroenterology. - 2003. - Vol.98., No. 5. - P.968-974]. Topical application of 0.2% glycerol trinitrate (drugs Nifedipine, Isoket"), according to the authors, allow "chemical sphincterotomy", lowering the tone of the internal sphincter at rest. According to the authors, the method allows to achieve relaxation of the internal sphincter combined with the improvement of microcirculation in the bowel wall.

A. Luck, P. Hewet (1999), and F. Altomare et al. (1999) suggested the use of glycerol trinitrate as a complement to surgery for excision of cracks without sphincterotomy, evaluating the effectiveness of the method in 65-70% [Luck A., Hewet P. Paste vs. lateral sphincterotomy for chronic anal fisure. - Diseases Colon Rectum. - 1999. - Vol.42. - P.4-9; F. Altomare et al. Glycerine Trinitrate for chronic anal fissure. - Diseases Colon Rectum. - 1999. - Vol.43. - P.124].

In recent years, been widely studied opioid peptides. A number of studies proved their ability to enhance the repair and regeneration of tissues, to improve regional microcirculation and lymph flow, to exert immunomodulatory effect, to enhance the activity STRESSOMETER systems. Identified diverse effects of opioids on visceral organs and systems. These properties are natural and synthetic analogue of LEU-enkefalina - dalargin, the clinical efficacy of which is revealed in the treatment of several diseases [Sirotin B.Z., Smernicki, O. Ushakov - Dalargin in treatment of ulcers in the diabetic foot syndrome. - Khabarovsk: DUGA, 2002, 80 C.]. There is evidence that dalargin (tyrosine-alanyl-glycyl-i.e. phenylalanyl-leucyl-arginine diacetate) increases production of prostaglandins in the mucous membrane of the intestines, normalizes microcirculation and lymph flow in the zone of injury [KAPYSHEV Akhmetov, GT Akhmetov, F manaeva Effect of dalargin on the healing of gastric and duodenal ulcers. - Therapeutic archive. - 1988. No. 8. - S-151]. In addition, dalargin effectively stimulates reparative processes in ulcerative lesions of the digestive tract, skin wounds. The peptide possesses immunomodulatory, anti-toxic, stress is a protective action in experimental animals and in humans. Its influence dalargin implements, as was established, intramuscular and intraperitoneal administration [Radius M, Zamaraev Century, Miller E., Vdovenko C. Theoretical foundations and practical perspectives for the use of opioid peptides in sports rehabilitation. - People in the sports world: New ideas, technologies and prospects: proceedings of the International Congress. - M., 1998. 1. - S-180]. In connection with the hydrolysis in the gastrointestinal tract dalargin not applicable oral and injected intramuscularly, intravenously, subcutaneously [S. Timoshin, Alekseenko S.A., a Piece A.A. Effect of dalargin on reparative ability of the gastroduodenal mucosa in patients with peptic ulcer of the duodenum. - Clinical medicine. - 1991. No. 3. - P.75-77].

Of patent and medical literature known methods of treatment of anal fissure.

There is a method of surgical treatment of anal fissure [Fedorov V.D., Dultsev J.V. Proctology. - M.: Medicine, 1984, 384 S.], providing surgical procedure under local anesthesia or General anesthesia. After insertion into the lumen of the rectum rectal mirrors, without effecting devolve sphincter, crack excised with "watchdog" bump within healthy tissue along with the affected anal crypt two semilunar incisions, while the bottom of the RA is s is the internal anal sphincter. After that, produce strictly on a 6-hour metered sphincterotomy to a depth of 0.8 cm in men and 0.5-0.6 cm in women.

The disadvantages of the method are:

1. The lack of adequate pharmacological denervation of the internal anal sphincter is not possible to eliminate it spasm in response to a bowel movement that hinders the healing process and increases the likelihood of relapse.

2. The method claimed by the authors of the modification involves a complete dissection of the posterior adhesions internal anal sphincter, which is a morphological reason for his failure.

3. After regeneration of the wound formed a rough scar, complicating the control of the discharge gases and mucous secretions.

4. Long term regeneration of the wound by secondary intention.

5. The absence of objective criteria dosing depth sphincterotomy.

There is a method of surgical treatment of anal fissures [inventor's Certificate SU 1149944 A, publication date: 15.04.1985] by excision and dosed dissection of the external sphincter, characterized in that, in order to prevent complications and relapses outer sphincter split by the width of the lengthwise into two pieces, then cut them in diametrically opposite directions on the distance from the crack, defect mucosa is sutured.

Method x the surgical treatment of anal fissure in the statement of the authors of the modification has the following disadvantages:

1. The lack of adequate pharmacological denervation of the internal anal sphincter is not possible to eliminate it spasm in response to a bowel movement that hinders the healing process and increases the likelihood of relapse.

2. The execute method does not take into account the individual characteristics of the inflammatory process and characteristics of regeneration in the wound.

3. When performing the method claimed by the authors of modification, without regard to constitutional features of the rectum, is highly likely to damage the upper branches pryamokishechnye artery bleeding, formation of hematomas and their subsequent secondary infection.

4. The message sphincterotomy wound gut predisposes to infection of wounds sphincter after the suturing of the defect of mucous.

5. The implementation of the method claimed by the authors of the modification is impossible in patients of older age groups, patients who underwent episiotomy, women with rectocele any degree, as well as prolapse of the pelvic floor, pelvic organ prolapse in patients with indurativnyy changes of the internal anal sphincter on a background of chronic inflammation.

Also known is a method of surgical treatment of anal fissure, the essence of which is that produce excision of anal fissure within healthy tissue on the back paleocrat the spine of the anus in the transverse direction in the form of a lunar Crescent, with the removal of adjacent external hemorrhoids dosed with subsequent excision of the internal sphincter in the same direction at a depth of 0.4 cm with suturing separately sphincter and skin and mucosal wounds to the transverse circular direction (RU # 2260383 C1 on 20.09.2005).

The disadvantages of the method are:

1. The lack of adequate pharmacological denervation of the internal anal sphincter is not possible to eliminate it spasm in response to a bowel movement that hinders the healing process and increases the likelihood of relapse.

2. The message sphincterotomy wound gut predisposes to infection of wounds sphincter after the suturing of the defect of mucous.

3. Excision of the area of the sphincter with its subsequent closure creates the opportunity for the development of incontinence due to the formation of rigid deforming scar or due to the eruption of the seams.

4. The execute method does not take into account the individual characteristics of the course of the wound process and does not address the elimination of inflammatory changes, dyscirculatory disorders and stimulate healing in the postoperative period.

5. Excision of the area of the sphincter without conducting functional assessment the switching apparatus of the rectum increases the probability of postoperative incontinence identified, according to the literature, 19.6-35% of cases [Shelygin Y.A., Zharkov E.E., Orlova, L.P., Podmarenkova L. F., Flights NN. The risk of anal incontinence after excision of anal fissure in combination with a lateral p is decornoy sphincterotomies. - Proctology. - 2005. No. 1(11). - P.10-16].

There is a method of surgical treatment of anal fissure [Method of anal fissure treatment. Patent number: MD2698F, Publication date: 2005-02-28]after excision of anal fissure, final hemostasis of the wound and measured sphincterotomy of the external sphincter in front semicircle impose a separate host seams between the mucous membrane of the rectum and the middle of the bottom of the wound in the longitudinal direction, at an angle of 45° on both sides of the crack.

The disadvantages of the method are:

1. The lack of adequate pharmacological denervation of the internal anal sphincter is not possible to eliminate it spasm in response to a bowel movement that hinders the healing process and increases the likelihood of relapse.

2. When performing the method inevitably formed extensive wound surface with a high risk of secondary infection in conditions of suturing.

3. After regeneration of the wound is formed by deforming scar on the front of the semicircle of the anal sphincter, which is a morphological cause of dyspareunia in women.

4. The execute method does not take into account the individual characteristics of the course of the wound process and does not address the elimination of inflammatory changes, dyscirculatory disorders and stimulate healing in the postoperative period.

On both the spine of the characteristics closest to the claimed method is a method of treatment of chronic anal fissure [RU No. 2216283 C1 from 20.11.2003], is its prototype.

When performing the method, including excision of anal fissure, previously conducted clinical and instrumental examination of the patient to determine the increased risk of anal incontinence and the presence of at least one of the following symptoms: reduced depth of the anal funnel, stress incontinence, anterior rectocele any degree, a history of long labor or childbirth large 4000 g fruit, rupture or dissection of the perineum during childbirth, more than one birth, age older than 55 years, when defecography - prolapse of the pelvic floor at natureway more than 4 cm, anorectal manometry is an increase in the amplitude of the relaxation of the internal sphincter more 26 mm Hg, increase relaxation of the internal sphincter more than 15 s, the reduction of pressure in the anal canal at the level of the external sphincter is less than 18 mm Hg, a decrease in the amplitude of contraction of the external sphincter less than 4.8 mm Hg, when sphincterotomy - reducing power of volitional contractions in men less than 570 grams at 3 and 9 and less than 510 g at 6 and 12 hours, for women less than 520 grams at 3 and 9 hours and less than 385 g at 6 and 12 hours, the increase in time of the excitation on both nerve more than 2.4 MS, surgical intervention limit excision of anal fissure and applied to the perianal skin is around the opening of the anus 0,3% nitroglycerine ointment, to apply the ointment should be repeated after 12 hours within 2-8 weeks.

The method revealed the following weaknesses:

1. The application of the method developed for populations at higher risk of anal incontinence, does not provide comprehensive medical intervention for mild inflammatory changes and stimulation of reparative processes in the wound.

2. The choice of the dosage form 0,2% nitroglycerine ointment is not possible to clearly measure used glycerol trinitrate, which is the active ingredient.

3. The proposed method of application of nitroglycerine ointment is applied to the perianal skin around the anus does not provide adequate absorption of the drug wound surface and the mucous membrane of the anal canal.

4. Application of the method does not allow for non-surgical treatment of anal fissure at high risk of postoperative incontinence by using glycerol trinitrate in combination with anti-inflammatory drugs, analgesics, the myotropic antispasmodic agents and means of stimulating regeneration.

5. In the method-prototype no differences in therapeutic tactics depending on the phase and degree of activity of inflammation, the nature of the morphological changes in the crack.

p> 6. This method was developed for chronic anal fissure and cannot be applied for the first time caused severe cracks.

The objective of the invention is the use of differential algorithm of conservative treatment of anal fissure, allowing to prevent the development of anal sphincter insufficiency, local inflammatory complications and postoperative recurrence of the disease.

The technical result - increase of efficiency of treatment of patients with anal fissures due to the prevention of the recurrence of cracks and the development of anal sphincter insufficiency through a combination of therapeutic treatments (including surgical manipulations), aimed at relaxation of the sphincter, the elimination of inflammation and stimulation of regeneration.

This object is achieved in that conduct a histological examination of the surgical preparation, identify if the 1st phase of the wound healing process, the complex conservative therapy includes oral administration of Pinnawela bromide 50 mg 3 times daily for 10 days, the introduction of candles and ointment preparations containing non-steroidal anti-inflammatory means 2 weeks, and transanal local instillation of 2.0 ml of 0.1% solution of glycerol trinitrate 2 times a day for 6 weeks. If you reveal 2 phase of wound process, complex conservative therapy includes the oral administration of mebeverine hydrochloride 200 mg 3 times a day for 2 weeks and additionally intramuscular injection of dalargin 1 mg 2 times a day for 2 weeks. If you reveal 3 phase of wound process, complex conservative therapy includes oral administration of mebeverine hydrochloride 200 mg 2 times a day for 2 weeks, addition of dalargin 2 mg intramuscularly 2 times a day for 2 weeks and transanal local instillation of 2.0 ml of 0.1% solution of glycerol trinitrate 2 times a day for 4 weeks.

The method is as follows. Determine the duration of the disease, evaluate the pre-treatment and its effectiveness, measure the level of the basal pressure in the anal canal in the projection of the internal sphincter, the average pressure in the anal canal during volitional contraction, on the basis of objective physical and instrumental (anoscopy) studies reveal the absence or the presence of comorbid chronic hemorrhoids and its stage. Performed the histological examination of the smear-fingerprint, biopsy, or surgical preparation. If the histological pattern of the drug corresponds to the 1 phase of wound healing, the complex conservative therapy includes: oral micropig antispasmodics - Pinnawela bromide 50 mg 3 times daily for 10 days, the introduction of candles and ointment preparations containing non-steroidal anti-inflammatory remedies, 2 weeks, and transanal local instillation of 2.0 ml of 0.1% solution of glyceryltrinitrate - 2 times a day for 6 weeks.

If the histological pattern of the drug corresponds to the 2 phase of wound healing, the complex conservative therapy includes: oral non-steroidal anti-inflammatory funds with a pronounced analgesic effect, local purpose candles (ointments)containing analgesics and antiseptics, oral antispasmodics myotropic - mebeverine hydrochloride 200 mg 3 times a day for 2 weeks, intramuscular injection of dalargin 1 mg 2 times a day for 2 weeks.

If histological evaluation of pathological changes corresponds to the 3 phase of wound healing, the complex conservative therapy includes: oral non-steroidal anti-inflammatory drugs, local purpose candles (ointments)containing analgesics and antiseptics, oral administration of mebeverine hydrochloride 200 mg 2 times a day within 2 weeks of dalargin 2 mg intramuscularly 2 times a day for 2 weeks, and transanal local instillation of 2.0 ml of 0.1% solution of glycerol trinitrate - 2 times a day for 4 weeks.

The dosage and the frequency of the local use of candles (ointments), as well as dosage and frequency of oral application of non-steroidal anti-inflammatory drugs is determined individually. The criteria for the effective dosage, crtn the STI introduction (in the absence of side effects) is a lower level of average pressure in the anal canal during volitional contraction after 2 days of medication compared with the original data.

The use of the proposed method is illustrated by the following examples.

Example 1. Patient A., 39 years old, medical history, No. 9319/472, was admitted to the Department koloproktologicheskih clinic Rostov state medical University 19.12.2005 year with complaints of intense periodic nagging pain in the back passage, increasing during defecation and after him. From the anamnesis it is known that he was about 4 months to see the doctor regarding this disease is not treated, the treatment was not carried out. An objective examination, on a 6-hour conditional of the dial on the back in the anal canal is defined by the rear crack sizes 1,2×0,4×0.5 cm, with elastic edges, rectal examination moderately painful. Other colorectal diseases, including hemorrhoids, is not revealed. The basal level of pressure in the anal canal in the projection of the internal sphincter - 100 cm water column, the average pressure in the anal canal during volitional contraction - 175 cm water column. On the basis of obtained data the indications for surgical treatment, 21.12.2005 year, performed excision of anal fissure in combination with lateral dosed sphincterotomies (Protocol operation No. 331), the histological pattern of drug corresponded to the 1 phase of wound healing, as evidenced by expressed exsd the tion, the presence of lymph histiocytomas infiltration, the patient is assigned to the complex conservative therapy according to the developed method, including oral appointment of Pinnawela bromide 50 mg 3 times daily for 10 days, the introduction of suppositories containing non-steroidal anti-inflammatory means 2 weeks, and also was organized by local transanal instillation 2.0 ml of 0.1% solution of glycerol trinitrate - 2 times a day for 6 weeks. Later, 2 days after the start of treatment, the level of basal pressure in the anal canal in the projection of the internal sphincter was 76 cm water column, the average pressure in the anal canal during volitional contraction - 117 cm column of water, the pain was cropped and not subsequently occurred. The patient was discharged from hospital 29.12.2005 year with recommendations for the outpatient treatment of complaints when the extract did not show. Against the backdrop of ongoing under the proposed method of drug therapy within 6 weeks marked healing of cracks. At the control examination 12.02.2006 year of hypertonic sphincter relapse cracks no other anorectal pathology it is not revealed. 3, 6, and 9 months after discharge at follow-up visits data no recurrence of the disease.

Example 2. Patient S., 49, case history No. 9120/459, was admitted to the Department koloproktologicheskih clinic Rostov state medical University is eritea 12.12.2005 year with complaints of pain in the anus during defecation and after him, poor selection of red blood after each defecation. From the anamnesis it is known that he was about 6 months - from June 2006, the previously held outpatient treatment without effect. On physical examination at 6-hour conditional of the dial on the back in the anal canal is defined by the rear crack 1.5×1,0×0.5 cm, with dense edges, rectal examination sharply painful. The basal level of pressure in the anal canal in the projection of the internal sphincter - 106 cm column of water that exceeds the upper limit of normal by 16.7%. The average pressure in the anal canal during volitional contraction - 198 cm column of water that exceeds the upper limit of normal 54.8%, i.e. more than 50%. Other colorectal diseases, including hemorrhoids, is not revealed. On the basis of obtained data the indications for surgical treatment, 14.12.2005 year, performed excision of anal fissure in combination with lateral dosed sphincterotomies (Protocol operation No. 320). The histological pattern of drug isecheno cracks and surrounding tissues revealed inflammation with marked sclerosis, angiomatosis stroma, inflammatory proliferation of squamous epithelium, which corresponded to the 2 phase of wound healing.

A day after the surgery scheduled and initiated complex conservative therapy developed according to the method, including oral non-steroidal anti-inflammatory funds with a pronounced analgesic effect, local purpose candles containing analgesics and antiseptics, oral administration of mebeverine hydrochloride 200 mg 3 times a day for 2 weeks, intramuscular injection of dalargin 1 mg 2 times a day for 2 weeks. Later, 2 days after the start of treatment, the level of basal pressure in the anal canal in the projection of the internal sphincter was 102 cm water column, the average pressure in the anal canal during volitional contraction 177 cm column of water, the pain was cropped and not subsequently occurred. The postoperative period was uneventful, with no complications. In the absence of complaints 22.12.2005, the patient was discharged from the hospital with recommendations for further treatment by the proposed method on an outpatient basis. Against the backdrop of ongoing under the proposed method of drug therapy within 2 weeks marked postoperative wound healing and epithelialization of the mucosal defect. 3, 6, and 9 months after discharge at the control examinations of complaints the patient is not present, the indicators anal manometry was consistent with normal values, the data for the no recurrence of the disease.

Example 3. Patient G., aged 44, case history No. 9347/474, was admitted to the Department koloproktologicheskih clinic Rostov state the endowment of the medical University 19.12.2005 year with complaints of intense constant pain in the back passage, growing during defecation and within 2-3 hours after, scarce periodic blood in the stool. From the anamnesis it is known that he was about 10 years previously undertaken outpatient drug treatment was temporary, unstable effect, bringing relief to no more than 7-10 days. On physical examination at 6-hour conditional of the dial on the back in the anal canal is defined by the rear crack size 1,0×0,2×0.3 cm, with dense robovie edges, "guard mound", a rectal examination is sharply painful. The basal level of pressure in the anal canal in the projection of the internal sphincter - 89 cm water column, which corresponds to normal values. The average pressure in the anal canal during volitional contraction - 149 cm column of water that exceeds the upper limit of normal 16.5%, i.e. more than 15%. The patient was diagnosed concomitant disease - chronic hemorrhoids 1 stage. On the basis of obtained data the indications for surgical treatment, 21.12.2005 year, performed excision of anal fissure without performing sphincterotomy (Protocol operation No. 336). The histological pattern of drug isecheno cracks and surrounding tissues revealed the presence of dense ANO-cutaneous scar, chronic inflammation, sclerosis, angiomatosis, which corresponded to 3 phase renew the process.

A day after the surgery scheduled and initiated complex conservative therapy according to the developed method, including oral nonsteroidal anti-inflammatory drugs, local purpose candles containing analgesics and antiseptics, oral administration of mebeverine hydrochloride 200 mg 2 times a day within 2 weeks of dalargin 2 mg intramuscularly 2 times a day for 2 weeks, and transanal local instillation of 2.0 ml of 0.1% solution of glycerol trinitrate - 2 times a day for 4 weeks.

Later, 2 days after the start of treatment, the level of basal pressure in the anal canal in the projection of the internal sphincter was 87 cm water column, the average pressure in the anal canal during volitional contraction - 137 cm column of water, the pain was cropped and not subsequently occurred. The postoperative period was uneventful, with no complications, 30.12.2005, the patient was discharged from hospital with recommendations for further treatment by the proposed method on an outpatient basis. Against the backdrop of ongoing under the proposed method of drug therapy within 4 weeks marked postoperative wound healing and epithelialization of the mucosal defect. 3, 6, and 9 months after discharge during the control examination of complaints, the patient is not present, the indicators anal manometry sootvetstvuyuschim values, data no recurrence of the disease.

Application of the proposed method contributes to the effectiveness of conservative treatment of chronic anal fissure, enables rational drug therapy in the postoperative period, contributing to more rapid rehabilitation of patients and to reduce the frequency of recurrence of the disease.

The method of treatment of anal fissure, including excision of anal fissure and complex conservative therapy, including rectal administration of suppositories and ointment preparations containing non-steroidal anti-inflammatory drugs, within 2 weeks, characterized in that conduct histological examination of the surgical preparation, and 1 phase of wound healing complex conservative therapy supplemented by oral administration of Pinnawela bromide 50 mg 3 times daily for 10 days and local transanal the instillation of 2.0 ml of 0.1%solution of glycerol trinitrate 2 times a day for 6 weeks; and when 2 phase of wound healing by oral administration of mebeverine hydrochloride 200 mg 3 times a day for 2 weeks and intramuscular injection of dalargin 1 mg 2 times a day for 2 weeks; and 3 phase of wound healing by oral administration of mebeverine hydrochloride 200 mg 2 times a day for 2 weeks, dalargin 2 mg intramuscularly 2 times sucky 2 weeks and local transanal the instillation of 2.0 ml of 0.1%solution of glycerol trinitrate 2 times a day for 4 weeks at 2 and 3 phases of wound healing complex conservative therapy includes oral administration of non-steroidal anti-inflammatory drugs.



 

Same patents:

FIELD: biology, medicine, organic chemistry.

SUBSTANCE: invention proposes compound of the general formula (I): wherein A means effector group; L means a linker link; B represents Skulachev-ion Sk or charged hydrophobic peptide. Compound can be used in preparing a pharmaceutical composition for target (directed) delivery of active substances in mitochondria carried out by electrochemical potential of hydrogen ions into mitochondria. Also, invention can be useful in treatment of diseases and states associated with disturbance of normal function of mitochondria, in particular, diseases associated with increased formation of free radicals and active forms of oxygen. The claimed invention owing to directed accumulation of biologically active substance in mitochondria provides enhancing the effectiveness of substance, to decrease total dose, probability and strength of adverse effects.

EFFECT: improved and valuable properties of method and pharmaceutical composition.

26 cl, 14 dwg, 16 ex

FIELD: medicine, pharmacology, pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to a solid pharmaceutical composition used in treatment of cyclooxygenase-2-dependent disorder or state that comprises from 200 mg to 400 mg of 5-methyl-2-(2'-chloro-6'-fluoroaniline)-phenylacetic acid and excipients wherein level of residual moisture in composition is from 1.5% to 5%. Also, invention relates to a method for stabilization of 5-methyl-2-(2'-chloro-6'-fluoroaniline)-phenylacetic acid as a component of the solid pharmaceutical composition that involves preparing the solid pharmaceutical composition comprising 5-methyl-2-(2'-chloro-6'-fluoroaniline)-phenylacetic acid wherein the composition comprises the level of residual moisture from 1.5% to 5%. The dried granulated preparation comprises 5-methyl-2-(2'-chloro-6'-fluoroaniline)-phenylacetic acid, microcrystalline cellulose, lactose monohydrate, croscarmellosa sodium wherein the level of residual moisture in the granulated preparation is from 2.5% to 4.5%. Solid pharmaceutical compositions comprise indicated dried granulated preparation. Invention provides enhancing stability of 5-methyl-2-(2'-chloro-6'-fluoroaniline)-phenylacetic acid as component of compositions and preparations.

EFFECT: improved and valuable properties of pharmaceutical compositions.

31 cl, 3 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: means comprises two complexes. Morning complex comprises soft tonic and biostimulating vegetable ingredients and vegetable adaptogen complex. Evening complex comprises soft vegetable ingredients of tranquilizing and sedative action stimulating cellular resources recovery. Beside that, the evening and morning complex comprise vitamins, mineral substances, antioxidants and specific biologically active substances directed to correction of specific organ or system disorders arising as a result of chronic desynchronosis. Method involves applying chronobiological correction means selecting their application time to match individual biorhythm phase peaks.

EFFECT: improved tolerance to transmeridional flight loads.

7 cl

FIELD: medicine.

SUBSTANCE: the present innovation deals with decreasing the intake of calories, the intake of food and appetite in a subject. The method deals, also, with peripheral introduction of therapeutically efficient quantity of PYY3-36 or its agonist, thus, decreasing the intake of calories by a subject. The advantage of the present technique deals with increasing the efficiency in decreasing body weight in such persons.

EFFECT: higher efficiency.

48 cl, 9 dwg, 6 ex

FIELD: medicine, in particular therapy.

SUBSTANCE: claimed method includes peroral administering of preparation from brown algae at least two time per day. Said preparation represents gel form homogenized brown algae having particle size 500 mum or less and containing at least 15 mg/kg of iodine and carbohydrate fractions: mannat 133.4±12.1 mg/g, alginic acid 147.8±10.7 mg/g. Preparation is administered for 30 min before eating in amount of 1-5 g/kg/day. Daily dose is 50-250 g. Course of treatment is 4-24 weeks.

EFFECT: preparation of increased antioxidant and immunomodulating action.

6 cl, 3 tbl, 6 ex

FIELD: medicine, veterinary science, agriculture, biotechnology.

SUBSTANCE: the present innovation refers to preparations of medicinal and veterinary indication and methods for their obtaining. The suggested complex preparation-probiotic includes a carrier being a porous aluminum oxide-based enterosorbent SUMS-1 and cells of bacteria-eubiotics with nutritive and protective media immobilized upon the mentioned carrier-enterosorbent. The cells of bacteria-eubiotics with nutritive medium are being a lyophilized concentrate of the consortium of either bifidobacteria or lactobacteria, or their mixture at titer being 108-1010 CFU/g, and as a porous carbon-modified enterosorbent SUMS-1 it contains enterosorbent SUMS-1 additionally treated with the solution of metal salt at the following ratio of the preparation components in lyophilized form, weight%: cells with nutritive medium of the consortium of bifido-, or lactobacteria-eubiotics, or their mixture with titer of 108-1010 CFU/g 1.0-10.0; protective medium 0.1-10.0; enterosorbent SUMS-1 additionally treated with the solution of metal salt - the rest up to 100%. Method for obtaining the suggested preparation deals with treating a porous enterosorbent SUMS-1 with the solution of metal salt at volumetric ratio being 1:1, not more and its washing against a reagent with 2-3-fold volumes of distilled water followed by mixing enetrosorbent and bacteria-eubiotics with nutritive and protective media at the ratio of 1:1, not more to keep the mixture till complete immobilization of bacterial cells onto enterosorbent with its subsequent freezing and freeze drying before sterilization. As bacteria one should apply the concentrate of the consortium of bifidobacteria, or lactobacteria, or their mixture at titer being 108-1010 CFU/g. The suggested complex preparation-probiotic provides higher efficiency of sorption and desorption of bacterial cells with enterosorbent SUMS-1 that shows its clinical efficiency and higher colonization activity of bacteria-eubiotics.

EFFECT: higher efficiency.

9 cl, 5 ex, 2 tbl

FIELD: medicine, surgery.

SUBSTANCE: the present innovation refers to treating osseous cavity in patients with chronic post-traumatic osteomyelitis, so, after necrsequestrectomy one should irrigate an osseous cavity with aqueous solution of sodium chloride, then it is necessary to treat the cavity with 3%-hydrogen peroxide solution with subsequent removal of foam with 0.02%-chlorohexidine bigluconate aqueous solution. Then twice during 1 min it is necessary to treat osseous cavity with 0.9%-ozonized sodium chloride solution at ozone concentration being 9000-10000 mgl/l. After that, one should introduce the mixture of anti-infectious chemotherapeutic preparations along with ultrasound cavitation for 3 min at frequency of 40 kHz followed by treating the cavity with the flow of nitrogen monoxide for 5 min at concentration being 5000 mg/cu. m. The innovation enables to increase penetrating capacity of medicinal preparations due to matching the desired mode of cavitary treatment.

EFFECT: higher efficiency of antiseptic treatment.

1 ex

FIELD: biotechnology, molecular biology.

SUBSTANCE: invention proposes a polynucleotide VEGI-192a encoding polypeptide that inhibits growth of human vascular endothelial cells. Invention describes expressing vector comprising polynucleotide and E. coli cell-host comprising vector. Invention discloses polypeptide encoded by polynucleotide and fused protein based on indicated polypeptide. Invention describes polynucleotide encoding fused protein and expressing vector based on indicated polynucleotide. Invention discloses a pharmaceutical composition used for inhibition of angiogenesis based on polypeptide-inhibitor of growth of human vascular endothelial cells and polynucleotide encoding its. Invention describes therapeutic methods for inhibition of angiogenesis and suppression of tumor growth based on this composition. Invention describes an antibody raised to polypeptide that inhibits growth of human vascular endothelial cells. Using this invention provides novel forms of inhibitor of human growth of vascular endothelial cells and can be used in medicine.

EFFECT: valuable biological and medicinal properties of inhibitor.

27 cl, 27 dwg, 13 tbl, 34 ex

FIELD: medicine.

SUBSTANCE: method involves opening pyo-inflammatory focus. Rexod is introduced in addition to basic therapy. Rexod is introduced during the operation or immediately after the operation and then every day once a day intravenously in bolus dose. The drug is introduced during 4-5 days in physiologic saline or in 5% glucose solution at a dose of 0.2 mcg/kg of patient body weight.

EFFECT: enhanced effectiveness of treatment; improved general health state within a short period; reduced oxidation stress; prevented secondary active oxygen forms production.

3 tbl

FIELD: medicine.

SUBSTANCE: disclosed is application of Ximedon (N-(β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine) for treatment and prophylaxis of various intoxication.

EFFECT: preparation of large spectrum of action and inducing effect comparable with Phenobarbital effect.

2 tbl, 13 ex

FIELD: medicine, oncology, pharmacy, biochemistry.

SUBSTANCE: invention relates to peptides-containing medicinal preparations. Invention relates to using peptide of the formula QMTOVNOG representing analog of α-fetoprotein fragment from 472-d to 479-th amino acid. This peptide is able for selective trapping by tumor cells and to operate as vector molecule for directed delivery of anti-tumor preparations into tumor cells. Also, invention relates to conjugate of indicated peptide with doxorubicin wherein doxorubicin is added to peptide by through thioester bond covalently. Also, invention relates to a pharmaceutical composition used in treatment of oncology diseases that comprises conjugate of doxorubicin with peptide QMNOVNOG as a vector molecule and taken in the effective dose and a pharmaceutical carrier suitable for intravenous administration. Invention provides the selective effect of conjugate that allows expanding sphere for using the preparation. Invention can be used in medicine in treatment of oncology diseases of different etiology.

EFFECT: valuable medicinal properties of peptide and conjugate.

3 cl, 2 tbl, 6 dwg, 6 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention proposes a pharmaceutical composition used in treatment of patients suffering from cerebrospinal sclerosis. The composition comprises as an active component inhibitor of dipeptidyl peptidase IV (DPIV) of the general formula (I): wherein A means a residue of amino acid comprising at least one functional group in by-side chain; B means oligopeptide comprising up to 20 amino acids in its chain length, or polyethylene glycol of molecular mass up to 20000 g/mole, or optionally substituted organic amine, amide, alcohol, acid or aromatic compound comprising from 8 to 50 carbon atoms representing substituted or optionally substituted phenyl, benzyl, naphthyl, biphenyl and wherein a substitute can mean replacing with one or some groups of alkyl, alkenyl, alkynyl, mono- or multivalent acyl, alkanoyl, alkoxyalkanoyl or alkoxyalkyl as by-side groups; C means group of thiazolidine, pyrrolidine, cyanopyrrolidine, hydroxyproline, dehydroproline or piperidine bound by amide bond with the group A. In animal model study administration of inhibitor DPIV as isoleucylthiazolidine fumarate in the dose 1 mg/kg resulted to the absence of clinical symptoms of disease. In other experiments this inhibitor caused accelerating recovery and shoed anti-inflammatory effect also.

EFFECT: valuable medicinal and biochemical properties of inhibitors.

4 cl, 8 dwg, 14 ex

FIELD: medicine, otorhinolaryngology.

SUBSTANCE: in pre-surgical period it is necessary to fulfill submucous injection of imunofan into the middle nasal meatus. Moreover, additionally, starting since the 1st d of therapy one should daily inject intramuscularly 1 cu. cm imunofan. The course should last for 10 d. The innovation in question increases a patient's total immune status, prevents the relapses of polyps in nasal cavity and reconstruct nasal respiration.

EFFECT: higher efficiency of therapy.

1 ex, 1 tbl

FIELD: medicine, peptides.

SUBSTANCE: invention relates to osteogenic growth oligopeptides used as stimulators of hemopoiesis. Invention proposes using an oligopeptide of molecular mass in the range from 200 to 1000 Da, comprising one of the following sequence: Tyr-Gly-Phe-Gly-Gly, Met-Tyr-Gly-Phe-Gly-Gly used in preparing a pharmaceutical composition and enhancing mobilization of hemopoietic stem cells from many differentiation line into peripheral blood, in particular, CD34-positive hemopoietic stem cells. Advantage of the invention involves expanding field in using oligopeptides used in stimulation of hemopoiesis.

EFFECT: enhanced and valuable properties of oligopeptides.

34 cl, 2 tbl, 7 dwg, 4 ex

FIELD: medicine.

SUBSTANCE: method involves applying corticosteroid preparation instillations into conjunctival cavity. Cyclosporin is per os introduced in addition at a daily dose of 2.0-2.5 mg/kg twice a day.

EFFECT: enhanced effectiveness interrupting inflammatory eye tissue changes cascade in early postoperative period.

2 cl

FIELD: medicine, anesthesiology, resuscitation, field surgery, medicine of catastrophes.

SUBSTANCE: it is necessary to carry out combined intramuscular injection of toradol and dalargin, moreover, toradol should be injected every 4-6 h, and dalargin should be injected per 1 mg every 2-3 h. The innovation suggested enables to achieve quick adequate anesthesia under any conditions due to optimally matched combination of preparations and, also, the modes and techniques of their injection.

EFFECT: higher efficiency.

8 dwg, 2 ex, 5 tbl

FIELD: medicine, gastroenterology.

SUBSTANCE: before introducing ASA for white mice through the probe at the dosage of 200 mg/kg it is necessary to introduce intraperitoneally a peptide of Arg-Tyr-D-Ala-Phe-Gly formula for 5 d at the dosage of 100 mcg/kg. The innovation enables to create efficient protection of gastric mucosa against damaging action of ASA, decrease the quantity, the size and total area of ulcers.

EFFECT: higher efficiency.

2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: method involves introduced Tanacan 40 mg three times a day 3 months long course. Magne B6 is concurrently introduced at a dose of 2 pills twice a day during 40 days. Endonasal Dalargin electrophoresis is additionally applied daily for 15-20 min. The total treatment course is 12 procedures long.

EFFECT: accelerated menstrual and reproductive function recovery.

FIELD: medicine.

SUBSTANCE: method involves introducing medicinal mixture containing Lidocaine - 20-40 mg; Mexidol - 50-100 mg; Dalargin - 1-2 mg; Lidase - 16-32 units; Gemase 2500-5000 units and also a mixture containing: Lidocaine - 30-50 mg; Hystochrome (0.02%) - 2-4 mg; Lidase - 16-32 units into lymphatic region of injured eye orbit - into pterygopalatine fossa zone and retroaural zone alternatively in 4-5 h long pause in daily course of 6-8 procedures. Then 3-5 discrete plasmapheresis procedures are applied using no more than 20-25% of circulating plasma volume for exfusion with cellular mass being divided into two parts, one of which is activated by incubating with 3-6 mg of Polyoxydonium and the second one about 500-750 mg of Claforan at temperature of 36.8 37.0°С within 30-40 min. Ultraviolet radiation treatment is applied during reinfusion.

EFFECT: significant improvement of visual functions; stable prolonged remission period; improved lymph drainage and micro- and lymph circulation in carrying out lymphotropic therapy; increased antioxidant blood activity; inhibited free radical lipid peroxidation under ultraviolet radiation blood treatment.

FIELD: medicine, ophthalmology.

SUBSTANCE: since the first post-surgical day it is necessary to introduce perorally cyclosporin at a single dosage of 2 mg/kg body weight and methipred - 0.5 mg/kg once daily for about 6-12 mo. Combination of such a mode of introduction and dosages of preparations enables to decrease the frequency of transplant's detachment and its cataract after keratoplasty in children of high-risk group and, also, decrease toxicity of cyclosporin and methipred.

EFFECT: higher efficiency of prophylaxis.

1 ex

FIELD: organic chemistry, chemical technology, biochemistry, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein both X1 and X2 represent methylene; R3 represents -CR5=CHR6, and R5 and R6 in common with atoms to which R5 and R6 are bound form (C6-C12)-aryl wherein R3 is substituted optionally with 1-5 radicals of the formula: -X4OR9 wherein X4 represents a bond; R9 represents halogen-substituted (C1-C3)-alkyl, and R4 represents -C(O)X5R11 wherein X5 represents a bond, and R11 represents hetero-(C6-C6)-cycloalkyl-(C0-3)-alkyl; X3 represents group of formulae (a) , (b) or (c) wherein n = 0, 1 or 2; R20 represents hydrogen atom (H); R21 is chosen from group consisting of H, -C(O)R26, -S(O)2R26 wherein R23 is chosen from H and (C6-C12)-aryl-(C0-C6)-alkyl; R25 is chosen from H, (C6-C12)-aryl-(C0-C6)-alkyl or -X4S(O)2R26 wherein X4 has above given values; R26 is chosen from group consisting of H, (C6-C12)-aryl-(C0-C6)-alkyl; wherein X3 comprises optionally, except for, one substitute that being in alicyclic or in aromatic ring system represents a radical chosen independently from group consisting of -X6OR17 wherein R17 represents H, (C1-C6)-alkyl, and X represents a bond or (C1-C6)-alkylene; and its N-oxide derivatives, protected derivatives, individual isomers and mixtures of these isomers; and pharmaceutically acceptable salts and solvated of such compounds, its N- oxide derivatives, protected derivatives, individual isomers and mixtures of these isomers. Also, invention describes a pharmaceutical composition possessing inhibitory activity with respect to cathepsin S-proteases based on compounds of the formula (I), and compound of the formula (Ix) given in the invention description. Invention provides preparing novel compounds possessing useful biological properties.

EFFECT: improved preparing method, valuable medicinal and biological properties of compounds and pharmaceutical composition.

16 cl, 3 tbl, 17 ex

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