Compositions derived from Chinese herbal medicines, medicinal plants and extracts thereof, are provided for the treatment of animals infected with viruses, especially with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). More specifically, the compositions of the present invention are derived from various Chinese herbal medicines or medicinal plants which have a long history of human consumption. The compositions of the invention are obtained through specific techniques and have demonstrated outstanding efficacy for treating human HBV carriers and hepatitis C patients. Compositions according to the invention have also exhibited in vitro antiviral activities against murine leukemia virus (MuLV) and HIV. HIV is the virus known to cause acquired immunodeficiency syndrome (AIDS) in humans and AIDS presents special problems to the medical community which the present invention addresses. Preferred compositions contain the herbal ingredients AEGINETIAE HERBA, BLECHNI RHIZOMA, LESPEDEZAE HERBA, POLYGONI CUSPIDATI RHIZOMA, FORSYTHIAE FRUCTUS, and LIGUSTRI FRUCTUS, or contain the herbal ingredients AEGINETIAE HERBA, LONICERAE FLOS, PRUNELLAE SPICA, and LESPEDEZAE HERBA.

Modem medical science is constantly searching for new and more powerful agents to prevent, treat or retard bacterial and viral infections and cure the diseases they cause. Bacterial and viral infections of humans and domestic animals cost billions of dollars annually. Vast sums of money are spent each year by pharmaceutical companies to identify, characterize, and produce new antibiotics and antivirals to combat the emerging drug resistant strains which have become a serious problem. Reliable prophylactic treatments for disease prevention are also of major interest. Yet, despite the costs and efforts to identify treatments for viral infections, such as hepatitis and AIDS, effective therapies remain elusive.
Hepatitis is a disease of the human liver. It is manifested with inflammation of the liver and is usually caused by viral infections and sometimes from toxic agents. Hepatitis may progress to liver cirrhosis, liver cancer, and eventually death. Several viruses such as hepatitis A, B, C, D, E and G are known to cause various types of viral hepatitis. Among them, HBV and HCV are the most serious. HBV is a DNA virus with a virion size of 42 nm. HCV is a RNA virus with a virion size of 30-60 nm. See D. S. Chen, J. Formos. Med. Assoc., 95(1), 6-12 (1996).
Hepatitis B is a major health problem worldwide, especially in Asia and Africa. Approximately 300 million people are chronically infected with HBV worldwide. More than one million carriers of HBV are found in the United States. HBV infection is currently the main cause of liver cirrhosis and cancer. HBV carriers are not only long-term reservoirs of the virus but also may develop chronic liver disease and have a greatly increased risk of developing liver cirrhosis and cancer. The progression from chronic hepatitis B to cirrhosis is frequently insidious and occurs without a noticeable change in symptoms. Once the symptoms of cirrhosis or cancer are manifested, therapies are of little value.
Prevention of HBV infection is possible through vaccination which is safe and effective. However, vaccination is not effective in treating those already infected, i.e., carriers and patients. Many drugs have been used in treating chronic hepatitis B and none have been proven to be effective, except interferon. Treatment with interferon has limited success and has frequently associated with adverse side effects such as fatigue, fever, chills, headache, myalgias, arthralgias, mild alopecia, psychiatric effects and associated disorders, autoimmune phenomena and associated disorders and thyroid dysfunction. Treatment with interferon for sixteen (16) weeks has been shown to be effective with a sustained loss of viral replication in approximately 40% of hepatitis B patients. The great majority of responders had normal serum aminotransferase levels and relapse rates appeared to be low. See R. P. Perrillo, Digestive Diseases and Sciences, 38(4), 577-593 (1993). However, a higher long-term relapse rate (24%) was reported in Chinese patients with chronic hepatitis B who underwent interferon therapy. See A. S. F. Lok, H. T. Chung, V. W. S. Liu, & O. C. K. Ma, Gastroenterology, 105(6), 1833-1838 (1993).
Moreover, serum hepatitis B surface antigen (HBsAg) disappeared in 10 to 15% of patients treated with interferon. The loss of HBsAg coincided with the disappearance of HBV. Improvement in liver histology was sustained years later in HBsAg-negative patients. The lack of disease progression could thus conceivably result in the prevention of liver cancer when treatment is provided in the pre-cirrhotic stage of infection. See R. P. Perrillo, Digestive Diseases and Sciences, 38(4), 577-593 (1993).
Hepatitis C has been previously described as a non-A non-B hepatitis, which is caused by HCV. There are approximately 100 million HCV carriers worldwide. An estimated 3.5 million people have chronic hepatitis C in the United States. HCV infection will lead to liver cirrhosis and cancer with less clinical manifestation. Most hepatitis C patients do not have particular symptoms and can thus be easily overlooked until it is too late for therapy. This poses a potentially more serious problem than hepatitis B. HCV carriers also become long-term reservoirs of the virus and eventually develop chronic liver disease and have a greatly increased risk of developing liver cirrhosis and cancer. See D. S. Chen, Science, 262, 369-370 (1993).
No effective immunization is currently available, and hepatitis C can only be controlled by preventive measures such as improvement in hygiene and sanitary conditions and interrupting the route of transmission. At present, the only acceptable treatment for chronic hepatitis C is interferon which requires at least six (6) months of treatment. Initial treatment has a response rate of about 50%. However, half of those responding relapse after cessation of interferon treatment. Therefore, only about 25% of patients have a sustained response. See D. S. Chen, J. Formos. Med Assoc., 95(1), 6-12 (1996) and N. Terrault & T. Wright, New Engl. J. Med., 332(22), 1509-1511 (1995). Because the interferon therapy has limited efficacy and frequent adverse effects, a more effective regimen is needed.
AIDS is a deadly disease caused by HIV. It has been plaguing the world since the first description of the disease in 1981 and the discovery of its causative agent, HIV, in 1983. About 13 million people were infected with HIV worldwide in 1993 and the number has increased to about 21 million in 1996. See B. Jasny, Science, 260(5112), 1219 (1993) and P. Piot, Science, 272(5270), 1855 (1996).
Several drugs have been approved for treatment of this devastating disease, such as azidovudine (AZT), didanosine (dideoxyinosine, ddI), d4T, zalcitabine (dideoxycytosine, ddC), nevirapine, lamivudine (epivir, 3TC), saquinavir (Invirase), ritonavir (Norvir), indinavir (Crixivan), and delavirdine (Rescriptor). See M. I. Johnston & D. F. Hoth, Science, 260(5112), 1286-1293 (1993) and D. D. Richman, Science, 272(5270), 1886-1888 (1996
All drugs currently approved for AIDS treatment utilize inhibition of viral proliferation and are viral reverse transcriptase inhibitors or viral protease inhibitors. More protease inhibitors, such as nelfinavir and improved saquinavir, are in development. An AIDS vaccine (Salk's vaccine) has been tested and several proteins which are chemokines from CD8 have been discovered to act as HIV suppressors.
In addition to the above synthetic nucleoside analogs, proteins, and antibodies, several plants and substances derived from plants have been found to have in vitro anti-HIV activity, such as Lonicera japonica and Prunella vulgaris, and glycyrrhizin from Glycyrrhiza radix. See R. S. Chang & H. W. Yeung, Antiviral Research, 9, 163-175 (1988) and M. Ito, et al., Antiviral Research, 7, 127-137 (1987).
Despite all of the available pharmaceuticals for the treatment of HIV, there is still no cure for the deadly disease. HIV viruses continue to mutate and become resistant to existing drugs such as the reverse transcriptase and protease inhibitors. Recently, a therapy of using two (2) or three (3) anti-HIV drugs in combination has been found effective in significantly lowering the HIV loads in AIDS patients. The results have been promising. However, the virus continues to develop resistance to the drugs and the long-term outcome (survival and cure rates) is still unknown. Thus, the medical communities throughout the world continue to search for drugs that can prevent the HIV infections, treat the HIV carriers to prevent them from progressing to full-blown deadly AIDS, and treat the AIDS patients.
Herbal Medicines
The use of herbal drugs and folk medicines have been known for thousands of years in China. These herbal approaches to the treatment of numerous illnesses, from arthritis to viral infections, have been previously viewed by western medicine as ineffective and dangerous. During the 19th century, many home remedies containing herbs were patented and sold. Modern drugs have replaced those remedies, but many modern drugs contain ingredients derived from herbs. For example, in 1776 the English botanist and physician William Withering learned that an herbal tea made by an old farm woman was effective in treating dropsy, or excess water in the tissues, which is caused by the inability of the heart to pump strongly enough. He found that one ingredient of the tea, which was made from leaves of the foxglove plant, strengthened the heart's pumping ability. The drug made from the foxglove plant is now known as digitalis.
Folk medicine is a relatively modern term to the West and has come to mean the care and treatment of the sick through a variety of herbal medicines. In recent years, folk medicines have become of increasing interest to many people in the western scientific medical community.
Prior Art--Herbal Medicines
A Chinese herbal medicine known as AEGINETIAE HERBA (a.k.a., GOLDEN LOCK KEY or LOTUS HERBA); has traditionally been used to treat illnesses such as swollen and sore throat, urinary tract infection, osteomyelitis, boil, tonsillitis, goiter, pharyngitis, thyroiditis, enteritis, liver disease, cancer, rheumatism, hematemesis, neurasthenia, eye redness, piles, menstruation irregularity, dropsy, jaundice, hernia, snake bite, and child developmental retardation. AEGINETIAE HERBA is prepared from the dried whole plant of Aeginelia indica which belongs to the family of Orobanchaceae. Dichondra micrantha, Striga lutea and Dichondra repens are also used to prepare this herbal medicine. Treatment dosage using the dried plant is typically from 4 to 150 g per day. It should be noted that the plant tastes bitter and is toxic.
Okubo et al. disclose that a phosphate buffered saline (PBS) extract (pH 7.2 at ambient to 4.degree. C.) from the seeds of Aeginetia indica exhibits excellent carcinostatic effect and possesses interleukin-2 and interferon-.gamma. inducing potency. The PBS was a 0.1 M phosphate buffered physiological saline at pH 7.2, not containing calcium or magnesium ions. The extracted substance is taught to be a macromolecular polysaccharide which may or may not contain lipid A binding with protein depending on whether the extraction is conducted using butanol or phenol. The extracted substance was soluble in water and insoluble in n-butanol. Its molecular weight was within the range of 100,000 to 200,000 dalton. See S. Okubo, M. Sato, & K. Himeno, U.S. Pat. No. 5,366,725, issued on Nov. 22, 1994.
A Chinese herbal medicine known as BAPHICACANTHIS RHIZOMA ET RADIX has traditionally been used to treat numerous illnesses such as fever, abscess, erysipelas, swollen sore throat, headache, jaundice, plague, leucorrhea, and syphilis. BAPHITCACANTHIS RHIZOMA ET RADIX is prepared from the dried rhizoma and root of Baphicacanthes cusia, Strobilanthes cusia, Isatis tinctoria, Isatis indigotica, or Polygonum tinctorium. It has been reported that this herbal medicine has exhibited inhibition of flu virus in vitro. A decoction from boiling the root of Isatis tinctoria in water has also exhibited antibacterial effect. Baphicacanthes cusia and Strobilanthes cusia belong to the family of Acanthaceae. Isatis tinctoria and Isatis indigotica belong to the family of Cruciferae. Polygonum tinctorium belongs to the family of Polygonaceae. Treatment doses are typically 10 to 19 g per day for BAPHICACANTHIS RHIZOMA ET RADIX.
Ho et al. disclose the use of an extract from a mixture of herbs including Isatis tinctoria for the in vitro inhibition of HIV infection in human T lymphocyte cells and mononuclear phagocytic lineage cells. The activity was based on the test results of a water extract from a mixture of three herbs: Isatis tinctoria (or Isatis indigotica), Lonicera japonica, and Polygonum bistorta. See D. D. Ho & X. S. Li, U.S. Pat. No. 5,178,865, issued on Jan. 12, 1993.
A compound known as tryptanthrin has been identified as the principal antifungal agent in the leaf of Strobilanthes cusia and as the main antidermatophytic substance in the leaf of Polygonum tinctorium and Isatis tinctoria. See H. Y. Hsu, Y. P. Chen, & M. Hong, The Chemical Constituents Of Oriental Herbs, Vol. 2, Oriental Healing Arts Institute, Los Angeles, Calif., U.S.A., 758-759 (1985).
The Chinese herbal medicine known as BLECHNI RHIZOMA, which is also known as DRYOPTERIS CRASSIRHIZOMAE RHIZOMA has traditionally been used to treat illnesses such as cut injury, swelling, fever, measles and erysipelas. BLECHNI RHIZOMA is prepared from the dried root and stem of Blechnum orientate which belongs to the family of Polypodiaceae or Blechnaceae. DRYOPTERIS CRASSIRHIZOMAE RHIZOMA is prepared from the dried root and stem of Dryopteris crassirhizoma which belongs to the family of Aspidiaceae. Osmunda japonica (Osmundaceae family), Woodwardia orientalis and Woodwardia unigemmata (Blechnaceae family), Athyrium acrostichoides (Aspidiaceae or Athyriaceae family), Sphaeropteris lepifera (Cyatheaceae family), Cyrtomium falcatum, and Cyrtomium fortunei (Aspidiaceae family) have also been used for preparation of these herbal medicines. These herbal medicines taste bitter and astringent and are slightly toxic. Treatment dosages are typically 4 to 11 g per day.
Blechnum orientate has also shown a strong inhibition effect against the influenza virus. Filmarone, filicin, aspidin, albaspidin, and filicic acid which are found in Dryopteris crassirhizoma have been characterized as having an anthelmintic effect. See H. Y. Hsu, Y. P. Chen, S. G. Hsu, J. S. Hsu, C. J. Chen, & H. C. Chang, Concise Pharmacognosy, New Medicine Publishing Co., Taipei, R.O.C., 577-578 (1985); and H. Y. Hsu, Y. P. Chen, & M. Hong, The Chemical Constituents Of Oriental Herbs, Oriental Healing Arts Institute, Los Angeles, Calif., U.S.A., 249-250 (1982).
Hozumi et al. disclose the rhizome of Dryopteris crassirhizoma as an antiherpesviral agent, antipolioviral agent, and anti-varicella-zoster virus agent. The rhizome of Cyrtomium fortunei and the rhizome of Woodwardia orientalis are also disclosed as antiherpesviral, antipolioviral, anti-measles virus, anti-varicella-zoster virus, and anti-cytomegalovirus (CMV) agents, as well as an anti-DNA and anti-RNA virus agent. See T. Hozumi, T. Matsumoto, H. Ooyama, T. Namba, K. Shiraki, M. Hattori, M. Kurokawa, & S. Kadota, U.S. Pat. No. 5,411,733, issued May 2, 1995.
A Chinese herbal medicine known as BLETILLAE TUBER has traditionally been used to treat illnesses such as hemoptysis, epistaxis, hematemesis, abscess, burn, dry and chapped skin, tuberculosis, gastric ulcer, and sores. BLETILLAE TUBER has astringent, antibacterial and antifungal properties. BLETILLAE TUBER is prepared from the dried tuber of Bletilla striata which belongs to the family of Orchidaceae. BLETILLAE TUBER tastes bittersweet, astringent and is nontoxic. Treatment dose is typically 2 to 11 g per day for an average human.
Chinese herbal medicines known as CIRSII RHIZOMA ET RADIX and BREEAE RADIX have traditionally been used to treat illnesses such as hematemesis, acute infectious hepatitis, cut bleeding, sores, and abscess. CIRSII RHIZOMA ET RADIX is prepared from the dried rhizoma or root or the whole plant of plants such as Cirsium japonicum, Cirsium albescens, and Cirsium japonicum var. australe which are from the Compositae family. BREEAE RADIX is prepared from the dried root of Compositae family plants such as Breea segetum (also known as Cephalanoplos segetum) and Breea setosum. Both herbal medicines taste sweet and slightly bitter, and are nontoxic. Treatment dose is typically 5 to 75 g per day for the average human.
A Chinese herbal medicine known as DICHONDRAE HERBA has traditionally been used to treat illnesses such as jaundice, dysentery, gonorrhea, dropsy, swollen boil, convulsion, encephalitis, rheumatism, hernia, diabetes mellitus, and hypertension. DICHONDRAE HERBA is prepared from the dried whole plant of Dichondra repens or Dichondra micrantha which belongs to the family of Convolvulaceae. The plant tastes bitter and is nontoxic. Treatment dosage of the dried plant is typically 10 to 40 g per day. Nine (9) compounds which were isolated from n-hexane and ethanol extracts of the whole herb of Dichondra micrantha have been identified. These compounds are maltol, umbelliferone, scopoletin, umbelliferone-7-O-glucopyranoside, scopolin, astragalin, isoquercitrin, kaempferol-3-O-rutinoside, and quercetin-3-O-rutinoside. See C.-J. Chou, L.-C. Lin, S.-Y. Hsu and C.-F. Chen, J. Chin. Med., 4(2), 143-149 (1993).
A Chinese herbal medicine known as FORSYTHIAE FRUCTUS has traditionally been used to treat illnesses such as sores, abscess, lymph node swelling, urethritis, and hypertension. It was also found to inhibit several bacteria and influenza virus. FORSYTHIAE FRUCTUS is prepared from the dried mature fruit of Forsythia suspensa, Forsythia viridissima, or Forsythia koreana which belong to the family Oleaceae. The herbal medicine tastes bitter and is nontoxic. Treatment dosage is typically 3 to 11 g per day.
Hozumi et al. disclose that the fruit of Forsythia suspensa is an antipolioviral agent and an anti-measles virus agent useful in treating these viral infections. See T. Hozumi, T. Matsumoto, H. Ooyama, T. Namba, K. Shiraki, M. Hattori, M. Kurokawa, & S. Kadota, U.S. Pat. No. 5,411,733, issued May 2, 1995.
The compounds forsythoside A (found in the leaf of Forsythia suspensa), forsythoside B (found in the stem of Forsythia koreana), and forsythoside C and forsythoside D (found in the fruit of Forsythia suspensa) have been reported to exhibit antibacterial activity against Staphylococcus aureus at a concentration less than 2 mM. Suspensaside (found in the fruit of Forsythia suspensa, likely the same as forsythoside C) has also been reported to exhibit antibacterial activity against Staphylococcus aureus Terashima with a minimum inhibition concentration (MIC) of 2.6 mg/mL. See H. Y. Hsu, T. P. Chen & M. Hong, The Chemical Constituents of Oriental Herbs, Vol. 2, Oriental Healing Arts Institute, Los Angeles, Calif., U.S.A., 53-55, 142-143 (1985).
A Chinese herbal medicine known as HEDYOTIS (also known as OLDENLANDIAE HERBA) has traditionally been used to treat illnesses such as urethra infection, pharyngitis, laryngitis, tonsillitis, subacute or chronic coccygodynia, appendicitis, intestinal cancer, contusion injury and eye disease. It has also been found to have weak antibacterial activity in vitro. HEDYOTIS is prepared from the dried whole plant of Hedyotis diffusa (also known as Oldenlandia diffusa) which belongs to the family Rubiaceae. The herbal medicine tastes sweet and is nontoxic. Treatment dosage is typically 19 to 300 g per day.
The Chinese herbal medicines known as LESPEDEZAE HERBA and SENECINIS HERBA have traditionally been used to treat illnesses such as urine incontinence, gonorrhea, asthma, stomach ache, general weakening and exhaustion, diarrhea, contusion injury, eye disease, eye redness, renal disease, acute inflammatory disease, cataract, dysentery, enteritis, jaundice, flu, septicemia, sore, swelling, and a disease of the palm. LESPEDEZAE HERBA is prepared from the dried whole plant of Lespedeza cuneata which belongs to the family Leguminosae. SENECINIS HERBA is prepared from the dried whole plant of Senecio scandens which belongs to the family Compositae. The extracts of Lespedeza cuneata and Senecio scandens have been shown to have an antibacterial effect. Both herbs taste sour, astringent and bitter. Treatment dose is typically 4 to 40 g per day.
A Chinese herbal medicine known as LIGUSTRI FRUCTUS has traditionally been used as a tonic and to treat illnesses such as insomnia, constipation, early white hair, neck lymph nodes tuberculosis and dropsy. LIGUSTRI FRUCTUS is prepared from the dried mature fruit of Ligustrum lucidum or Ligustrum japonicum which belongs to the family Oleaceae. The leaves of Ligustrum lucidum have been used as an antipyretic, analgesic, and anti-inflammatory agent. The leaves of Ligustrum japonicum have also been used to treat illnesses such as ophthalmalgia, ulcerative stomatitis, mastitis, swelling, and bum. The fruits of Ligustrum lucidum taste bitter and are nontoxic. Treatment dosage of the dried fruits is typically 6 to 20 g per day. That of the dried leaves is typically 40 to 75 g per day.
A Chinese herbal medicine known as LONICERAE FLOS has traditionally been used to treat illnesses such as fever, acute infectious diseases, measles, carbuncle, dysentery, enteritis, ringworm and similar skin diseases. LONICERAE FLOS is prepared from the dried flower bud of Lonicera japonica or Lonicera confusa. Both plants belong to the family Caprifoliaceae. The flower of Lonicera japonica has diuretic, antipyretic, anti-inflammatory, anti-convulsive, antibacterial and antiviral properties. The flower bud has also been used as a diuretic. The herbal medicine tastes sweet and is nontoxic. Treatment dosage is typically 11 to 75 g per day for the typical human.
Ho et al. disclose the anti-HIV activity in vitro of a mixture of Lonicera japonica, Isatis tinctoria (or Isatis indigotica) and Polygonum bistorta or a mixture of Lonicera japonica with Scutellaria baicalensis. Water extractions of the mixtures, treatment with ethanol precipitation and charcol adsorption are disclosed for the preparation of the anti-HIV active composition. See D. D. Ho & X. S. Li, U.S. Pat. No. 5,178,865, issued on Jan. 12, 1993. Several tannins such as caffeoylquinates isolated from Lonicera japonica have been reported to have an inhibitory effect on HIV-1 reverse transcriptase activity. See C.-W. Chang, M.-T. Lin, S.-S. Lee, K. C. S. C. Liu, F.-L. Hsu, & J.-Y. Lin, Antiviral Research, 27, 367-374 (1995).
A mixture of aqueous extracts of Lonicera japonica flower buds and Forsythia suspensa fruits with the crude flavonoids from Scutellaria baicalensis has been shown to have antibacterial and antiviral properties. A group of patients with severe respiratory disease were treated with the mixture and they responded as well as a control group on standard antibiotic therapy. See P. J. Houghton, Z. Boxu, & Z. Xisheng, Phytother. Res., 7, 384-386 (1993).
A Chinese herbal medicine known as PHELLODENDRI CORTEX has traditionally been used to treat illnesses such as dysentery, diarrhea, jaundice, stools with blood, abdominal pain, indigestion, bacteroid enteritis, and tuberculoid diarrhea. The herbal medicine has also been used to prepare an eye wash, for strengthening stomach and intestine to stimulate appetite, and as an astringent, anti-inflammatory, etc. It has antibacterial, anti-inflammatory, and wound healing properties. PHELLODENDRI CORTEX is prepared from the dried cortex of plants from the Rutaceae family such as Phellodendron amurense, Phellodendron chinense, Phellodendron amurense var. sachalinense, and Phellodendron wilsonii. PHELLODENDRI CORTEX tastes bitter and is nontoxic. Treatment dose is typically 1 to 11 g per day.
Hozumi et al. disclose the bark of Phellodendron amurense as antiherpesviral, antipolioviral, anti-measles virus, anti-varicella-zoster virus, and anti-CMV agents, as well as an anti-DNA virus and anti-RNA virus agent. See T. Hozumi, T. Matsumoto, H. Ooyama, T. Namba, K. Shiraki, M. Hattori, M. Kurokawa, & S. Kadota, U.S. Pat. No. 5,411,733, issued on May 2, 1995.
A Chinese herbal medicine known as POLYGONI CUSPIDATI RHIZOMA has traditionally been used to treat illnesses such as dysentery, menorrhagia, dysmenorrhea, dysuria, infantile growth retardation, and appendicitis. POLYGONI CUSPIDATI RHIZOMA is prepared from the dried rhizoma of Polygonum cuspidatum, Polygonum runcinatum, or Polygonum reynoutria (also known as Reynoutria japonica) which belong to the family Polygonaceae. The tender leaf has also been used to treat contusion and cut injuries. Extract of the herbal medicine has exhibited antibacterial and antiviral effects in vitro. Excessive use of the herbal medicine may cause a slight diarrhea. The herbal medicine tastes bitter and the treatment dose is typically 6 to 40 g per day.
Hozumi et al. disclose the root and rhizome of Polygonum cuspidatum as an antiherpesviral, antipolioviral, anti-varicella-zoster virus, and anti-CMV agent. See T. Hozumi, T. Matsumoto, H. Ooyama, T. Namba, K. Shiraki, M. Hattori, M. Kurokawa, & S. Kadota, U.S. Pat. No. 5,411,733, issued on May 2, 1995.
Resveratrol has been reported as an antifungal and antibacterial component in the root of Polygonum cuspidatum. See H. Y. Hsu, Y. P. Chen, & M. Hong, The Chemical Constituents Of Oriental Herbs, Vol. 2, Oriental Healing Arts Institute, Los Angeles, Calif., U.S.A., 51 (1985).
A Chinese herbal medicine known as PRUNELLAE SPICA has traditionally been used to treat illnesses such as goiter, hemorrhoids, swollen eye, ophthalmalgia, gonorrhea, uterine disease, mastitis, breast abscess, breast cancer, chronic arthritis, conjunctivitis, and hypertension. PRUNELLAE SPICA is prepared from the dried spica or whole plant of Prunella vulgaris or Prunella vulgaris subsp. asiatica (also known as Prunella vulgaris var. lilachina). Both plants belong to the family Labiatae. The whole plant can be used as a diuretic and also has antibacterial effect in vitro. The herbal medicine tastes bitter and is nontoxic. Treatment dosage is typically 4 to 110 g per day for the average human.
Hozumi et al. disclose the spike of Prunella vulgaris as an antiherpesviral agent for treating herpes virus infection. See T. Hozumi, T. Matsumoto, H. Ooyama, T. Namba, K. Shiraki, M. Hattori, M. Kurokawa, & S. Kadota, U.S. Pat. No. 5,411,733, issued May 2, 1995. The water extract of Prunella vulgaris (boiling 3 g in 100 mL water for 45 minutes) has also been reported to have anti-HIV (strain H9/3B) activity. The extract also exhibited synergistic anti-HIV activity with zidovudine (AZT) and didanosine (ddI). Only a slight additive effect was observed for Prunella vulgaris and zalcitabine (ddC). See J. F. John, R. Kuk, & A. Rosenthal, Abstr. Gen. Meet. Am. Soc. Microbiol., 94, 481(1994).
Yamasaki et al. evaluate in vitro two hundred four (204) crude drugs of common use in Japan for anti-HIV-1 activity and reported that the hot water extract of Prunella vulgaris (spike) showed a strong in vitro anti-HIV-1 activity with an IC.sub.100 of 16 .mu.g/mL. See K. Yamasaki, T. Otake, H. Mori, M. Morimoto, N. Ueba, Y. Kurokawa, K. Shiota, & T. Yuge, Yakugaku Zasshi, 113(11), 818-824 (1993).
Yao et al. reported that the water extract of the dried entire plant of Prunella vulgaris was active in vitro in inhibiting HIV-1 replication with relatively low cytotoxicity towards the MT-4 cells. The extract was also active in reverse transcriptase inhibition. The active factor was purified and identified as anionic with a molecular weight of approximately 10,000 dalton. This active component may be the same as the prunellin, as described below by Tabba, et al. The purified extract inhibited HIV-1 replication in the lymphoid cell line MT-4, in the monocytoid cell line U937, and in peripheral blood mononuclear cells (PBMC) at effective concentrations of 6, 30, and 12.5 .mu.g/mL, respectively. Pretreatment of uninfected cells with the extract prior to viral exposure did not prevent HIV-1 infection. Preincubation of HIV-1 with the purified extract dramatically decreased infectiousness. The purified extract was also able to block cell-to-cell transmission of HIV-1, prevented syncytium formation, and interfered with the ability of both HIV-1 and purified gp120 to bind to CD4. PCR (polymerase chain reaction) analysis confirmed the absence of HIV-1 proviral DNA in cells exposed to virus in the presence of the extract. The results suggested that the purified extract antagonized HIV-1 infection of susceptible cells by preventing viral attachment to the CD4 receptor. See X. J. Yao, M. A. Wainberg, & M. A. Parniak, Virology, 187(1), 56-62 (1992).
Tabba et al. isolated and partially characterized an anti-HIV component, prunellin, from aqueous extracts of dried inflorescence of Prunella vulgaris. Prunellin is a carbohydrate with an MIC (minimum inhibition concentration) of 2.2 .mu.g/mL against HIV-1 in vitro. It was identified as a partially sulfated polysaccharide with a molecular weight of about 10,000 dalton. See H. D. Tabba, R. S. Chang, & K. M. Smith, Antiviral Research, 11, 263-273 (1989).
Zheng evaluated four hundred seventy two (472) traditional medicinal herbs for antiviral effect on type 1 herpes simplex virus (HSV 1). Prunella vulgaris was one of the ten herbs found to be highly effective in vitro. Clinically, 78 cases of herpetic keratitis due to HSV1 were treated with Prunella vulgaris and Pyrrosia lingua eye drops. Among them, 38 cases were effectively cured, 37 cases showed an improvement, and 3 cases showed no benefit. See M. Zheng, J. Tradit. Chin. Med., 8(3), 203-206 (1988).
Triterpene 1 and triterpene 2 which have been isolated from Prunella vulgaris have shown antiviral activity against HSV1. Triterpene 1 was identified as betulinic acid and triterpene 2 was identified as 2.alpha., 3.alpha.-dihydroxyurs-12-en-28-oic acid. The EC.sub.50 was estimated to be 30 .mu.g/mL for triterpene 1 and 8 .mu.g/mL for triterpene 2 by plaque reduction assay. See S. Y. Ryu, C-K. Lee, C. O. Lee, H. S. Kim, & O. P. Zee, Arch. Pharmacal Res. (Seoul), 15(3), 242-245 (1992).
A Chinese herbal medicine known as SCUTELLARIAE BARBATAE HERBA has traditionally been used to treat illnesses such as hematemesis, gonorrhea with traces of blood, sores, cancer, convulsion, pneumonia, enteritis, coccygodynia, appendicitis, asthma, malaria, and rheumatism. It was also found to have antibacterial effect. SCUTELLARIAE BARBATAE HERBA is prepared from the dried whole plant of Scutellaria barbata, Scutellaria rivularis, or Scutellaria dependens which belong to the family Labiatae. The herbal medicine tastes bitter and should not be consumed by those who have anemia. Pregnant women should avoid taking this herb. Treatment dosage is typically 4 to 300 g per day.
Dried whole plants of Scutellaria rivularis have been used in folk medicine for the treatment of tumors, hepatitis, liver cirrhosis, and other diseases in China and Taiwan. See Y. L. Lin, Y. H. Kuo, G. H. Lee, and S. M. Peng, J. Chem. Research (S), 320-321 (1987).
Apigenin, isolated from the whole herb of Scutellaria rivularis, was found to have anti-influenza virus activity. See T. Nagai, et al., Chem. Pharm. Bull., 38(5), 1329-1332 (1990).
A Chinese herbal medicine known as SOLANI HERBA has traditionally been used to treat illnesses such as boil, acute nephritis, cancer and sores. SOLANI HERBA is prepared from the dried whole plant of Solanum nigrum which belongs to the family Solanaceae. The extract of SOLANI HERBA has demonstrated anti-inflammatory property. The fruit has also exhibited the effects of suppressing coughs and relieving bronchial inflammation. The herbal medicine tastes bitter and slightly sweet, and is nontoxic. Treatment dosage is typically 11 to 60 g per day.
The compound solasonine (found in the whole herb, fruit, leaf, and fresh immature berries of Solanum nigrum) has an anti-inflammatory effect similar to cortisone. Solasonine and solanine (also found in Solanum nigrum) possess the ability of raising or lowering the blood sugar level in rats depending on the situation of the animals. Solasonine was also reported to have a stimulating effect on the heart, while solanine had a suppressive effect. When administered at small doses, solasonine enhances the stimulative process of the central nerve system in animals (i.e., rat and rabbit). On the other hand, it enhances the suppressive process when administered at large doses. Solasonine can also lower the blood coagulability. See (1) H. Y. Hsu, Y. P. Chen, S. G. Hsu, J. S. Hsu, C. J. Chen, & H. C. Chang, Concise Pharmacognosy, New Medicine Publishing Co., Taipei, R.O.C., 176-177 (1985); (2) H. Y. Hsu, Y. P. Chen, & M. Hong, The Chemical Constituents Of Oriental Herbs, Oriental Healing Arts Institute, Los Angeles, Calif., U.S.A., 1400-1401, 1406 (1982); and (3) H. Y. Hsu, Y. P. Chen, & M. Hong, The Chemical Constituents Of Oriental Herbs, Vol. 2, Oriental Healing Arts Institute, Los Angeles, Calif., U.S.A., 742 (1985).
Combinations of herbal medicines such as LONICERAE FLOS, BAPHICACANTHIS RHIZOMA ET RADIX, and FORSYTHIAE FRUCTUS have been used as antipyretic and detoxification agents and for treating acute hepatitis. The herbal medicines BLECHNI RHIZOMA and POLYGONI CUSPIDATI RHIZOMA have been used along with other herbal medicines in a formula for treating Hepatitis B. The herbal medicines SCUTELLARIAE BARBATAE HERBA and LIGUSTRI FRUCTUS have occasionally been added with other herbal medicines into the above formula to improve the treatment. The herbal medicine LIGUSTRI FRUCTUS was occasionally used along with other herbal medicines mainly as a tonic and the herbal medicine HEDYOTIS has been occasionally used along with other herbal medicines as a detoxification agent. The herbal medicine PRUNELLAE SPICA has also been used along with other herbal medicines to relief liver stress.
Chang and Yeung screened the boiling water extracts of twenty seven (27) medicinal herbs for anti-HIV activity. They found eleven (11) of the extracts were active in inhibiting HIV in the H9 cells. Lonicera japonica, Prunella vulgaris, Woodwardia unigemmata, and Senecio scandens were among those active ones with moderate activities. Forsythia suspensa, Isatis tinctoria, and Polygonum cuspidatum were among those tested which did not display activity in the anti-HIV assay. The anti-HIV active extract of Viola yedoensis was further tested and found to be fairly specific. The extract did not inactivate HIV extracellularly and did not inhibit the growth of herpes simplex, polio, or vesicular stomatitis viruses in human fibroblast culture. See R. S. Chang & H. W. Yeung, Antiviral Research, 9, 163-175 (1988).
Antiviral agents have been isolated from Syzygium aromaticum, Sapium sebiferum, Scutellaria baicalensis, and Scutellaria rivularis. Eugeniin (a tannin) isolated from Syzygium aromaticum and methyl gallate isolated from Sapium sebiferum exhibited anti-herpes simplex virus activity in vitro. Plant flavenoids, such as 5,7,4'-trihydroxy-8-methoxyflavone from the root of Scutellaria baicalensis and apigenin (5,7,4'-trihydroxyflavone) from the whole herb Scutellaria rivularis, were also reported to have anti-influenza virus activity. See (1) T. Hozumi, et al., U.S. Pat. No. 5,411,733 (1995); (2) M. Takechi & Y. Tanaka, Planta Medica, 42, 69-74 (1981); (3) C. J. M. Kane, et al, Bioscience Reports, 8, 85-94 (1988); and (4) T. Nagai, et al., Chem. Pharm. Bull., 38(5), 1329-1332 (1990).
Hozumi et al. investigated ninety one (91) herbal medicines which demonstrated antiviral activity. More specifically, fifty two (52) of them had antiherpesviral activity, sixty four (64) had antipolioviral activity, thirty seven (37) had anti-measles virus activity, twenty seven (27) had anti-varicella-zoster virus activity, twenty three (23) had anti-CMV activity, and twenty eight (28) had anti-DNA virus and anti-RNA virus activity. See T. Hozumi, T.
Matsumoto, H. Ooyama, T. Namba, K. Shiraki, M. Hattori, M. Kurokawa, & S. Kadota, U.S. Pat. No. 5,411,733, issued on May 2, 1995. The anti-DNA virus and anti-RNA virus activity of the twenty eight (28) herbal medicines disclosed in the 5,411,733 patent was based upon their antiherpesviral, antipolioviral, anti-measles virus, and/or anti-varicella-zoster virus and anti-CMV activities. However, the extrapolation to cover both anti-DNA virus and anti-RNA virus activities is unfounded from the experiments conducted.
The data of the present invention, presented below, evidenced little or no anti-HIV activity of the two herbal medicines at 2.5 and 0.5 mg/mL derived from the rhizome of Cyrtomium fortunei and the bark of Phellodendron amurense. In contrast, the three (3) herbal medicines using the spike of Prunella vulgaris, the fruit of Forsythia suspensa, and the root and rhizome of Polygonum cuspidatum will be shown to have a strong to moderate anti-HIV activity at 2.5 mg/mL. Prunella vulgaris has also been reported by others as described above to have a very good anti-HIV activity.
It is noted that in the practice of traditional Chinese medicine, herbal medicines are used to treat the symptoms of the patients, not the disease or causative agent itself, and are therefore not known to be specific to a particular disease. Herbal medicines were prescribed depending on the symptoms of the individual patient. The composition of herbal medicines also vary case by case and may even change for each individual patient during the course of the treatment according to each treatment result. It is therefore very difficult to describe a particular herbal composition from the prior art suitable for treating a specific disease.
The present invention is directed to the discovery of antiviral herb compositions, extracts thereof and the active chemical constituents thereof. The antiviral herb compositions of this invention are derived from individual herbs, herb mixtures and commercially available Chinese herbal medicines. These novel herb compositions and their extracts and/or active principles are demonstrated herein as active against viral diseases such as HBV and HCV carriers, hepatitis B, hepatitis C, HIV infection and AIDS.

Compositions of matter useful in the treatment of viral infections derived from plant extracts


A multi-phase clock generator for receiving an external clock signal through a PLL and for generating a plurality of internal clock signals differing in phase from each other. The multi-phase clock generator includes two large gates whose outputs are the two internal clock signals, and two latch circuits for controlling the logic gate outputs. The output from the PLL is fed forward to the logic gates so that the rise of one internal clock signal is separated from a prior fall of the other internal clock signal by a period related to the frequency of the PLL output.

The present invention relates to a multi-phase clock generator circuit, and more particularly to a clock generator circuit having a phase lock loop for generating a plurality of synchronizing clock signals.
It had been known in the art to which the invention pertains that the phase lock loop is used for generating multi-phase internal clock signals from an external clock signal.
FIG. 1A is a circuit diagram illustrative of a conventional clock generator circuit having a phase lock loop. The clock generator circuit has a phase lock loop circuit 1A which receives an input of clock signals CL and generates an output of clock signals CAA which frequency is four times higher than the clock signals CL. The clock generator circuit also has 1/2 frequency divider circuit 2A which receives an input of the clock signals CAA and generates an output of clock signals CBA which is lower by two times than the clock signals CAA. The clock generator circuit also has logic circuits for generating two phase internal clock signals C1 and C2. The logic circuit has first and second AND gates 11 and 12 as well as first and second delay circuits 7 and 8 in addition an invertor circuit 13. The first AND circuit 11 has an output side which is connected to a first output terminal on which the first internal clock signal C1 appears. The second AND circuit 12 has an output side which is connected to a second output terminal on which the second internal clock signal C2 appears. The output side of the first AND circuit 11 is also connected to an input side of the second delay circuit 8. The output side of the second AND circuit 12 is also connected to an input side of the first delay circuit 7. The first delay circuit generates from the output side a delayed signal C7. The output side of the first delay circuit 7 is connected to one of the input terminals of the first AND gate 11. The output side of the 1/2 frequency divider circuit 2A is also connected to another input terminal of the first AND gate 11. The second delay circuit 8 generates from the output side a second delayed signal C8. The output side of the second delay circuit 8 is connected to one of the input terminals of the second AND gate 12. The output side of the 1/2 frequency divider circuit 2A is also connected to an input side of the invertor 13. The invertor 13 generates from an output side an inverted signal. The output side of the invertor 13 is connected to one of the input terminals of the second AND gate 12. The output side of the second delay circuit 8 is connected to the other input terminal of the second AND gate 12.
FIG. 1B is a circuit diagram illustrative of a first delay circuit provided in a conventional clock generator circuit having a phase lock loop of FIG. 1A. The first delay circuit 7 comprises a resistor R1 connected in series between the input and output sides, and a capacitor C1 connected between a ground line and the output side of the first delay circuit 7.
FIG. 1C is a circuit diagram illustrative of a second delay circuit provided in a conventional clock generator circuit having a phase lock loop of FIG. 1A. The second delay circuit 8 comprises a series connection of two invertor circuits 17 and 18 between the input and output sides as well as a capacitor C2 connected between the ground line and an intermediate point between the two invertor circuits 17 and 18. The invertor circuit 17 is connected to the input side whilst the invertor circuit 18 is connected to the output side.
FIG. 2 is a timing chart illustrative of waveforms of lock signals transmitting in a conventional clock generator circuit of FIG. 1A. The clock signal C1 is inputted into the phase lock loop circuit 1A whereby the external clock signal C1 is fourfold-multiplied to generate the signal CAA which is four times higher in frequency than the clock signal C1. The signal CAA is then inputted into the 1/2 frequency divider circuit 2A whereby the signal CAA is divided to generate the signal CBA. The first internal clock signal C1 falls in synchronization with the fall-timing of the signal CBA and rises in synchronous with the fall-timing of the first delayed signal C7 which is delayed by a time period TD1A from the fall-timing of the second internal clock C2. The second internal clock signal C2 fall in synchronization with the rise-timing of the signal CBA and rises in synchronization with the fall-timing of the second delayed signal C8 which is delayed by the time period TD1A from the fall-timing of the first internal clock C1. If the multiple phase internal clock signals are used, it is required to avoid any overlap of high level time periods of the multiple phase internal clock signals, for which purposes the first and second delay circuits 7 and 8 are provided to delay the rise-timings of the first and second internal clock signals C1 and C2.
The above conventional clock generator circuit has the following problems related to the first and second delay circuits 7 and 8. Variations in conditions for semiconductor manufacturing processes cause variations in the resistance value of the resistor R1 used in the first delay circuit 7 as well as variation in capacitance of the capacitors C1 and C2 used in the first delay circuit 7. Such variations can also cause variation in trans conductance of transistors used in the investors 17 and 18 of the second delay circuit 8. Furthermore, the resistance value of the resistor R1 and the trans conductance of transistors used in the invertors 17 and 18 are variable depending upon a temperature of the transistors in use. Moreover the trans conductance of transistors used in the invertors 17 and 18 is variable depending upon a power voltage for driving the circuit. A total amount of the variation in those parameters may be considerable. Considering that the total amount of the variation in those parameters has a maximum value, then the delayed time of the delay circuit may be varied by 50% or more. Such large variation in delay time of the delay circuit causes a large variation in duty of the first and second internal clock signals C1 and C2. This makes it difficult to set wide operational conditions of the semiconductor device.
In the above circumstances, it had been required to develop a novel multi-phase clock generator circuit with reduced variation in duty of internal clock signals.


A binder including a first cover and a second cover pivotally coupled to the first cover, both of the covers being generally flat and planar and having a first and second opposite sides thereof. The binder further includes a pocket coupled to the first cover, wherein the pocket can be accessed from both the first and second sides of the first cover.

Binders and other similar components may be used to store loose-leaf papers, bound notebooks, etc. Users of such notebooks also typically utilize handouts, papers, writing instruments and other accessories for use with the binder. Binders may include internal and/or external pockets for storing such components. However, access to internal pockets may be limited when the binder is in its closed position, and, conversely, it may be difficult or inconvenient to access the external pockets when the binder is in its open position. Accordingly, there is a need for a binder having a pocket which can be accessed from either inside and/or outside the binder.


A gas generator for a restraining device includes a housing formed by joining and integrating a diffuser shell having a gas discharge port and a closure shell, and a gas generating agent, an igniter, and a cylindrical filter, accommodated inside the housing. The housing has a top plate, a circumferential wall surface, and a bottom plate, and a plurality of protruding portions concaved inwardly and formed with a distance from each other on at least either of an upper annular corner portion located at a boundary portion between the top plate and the circumferential wall surface and a lower annular corner portion located at a boundary portion between the bottom plate and the circumferential wall surface. Part of the cylindrical filter is supported and fixed by the plurality of protruding portions, and a gap is provided between an outer circumferential surface of the cylindrical filter and the gas discharge hole.

1. Field of Invention
The present invention relates to a gas generator for a restraining device of a vehicle, such as an airbag apparatus.
2. Description of Related Art
In a gas generator in which a combustion chamber is formed inside a cylindrical filter, when the filter is attached to a predetermined position of a housing, the attachment has to be made with a certain restraining force to prevent the filter from becoming shaky or moving in subsequent assembling.
In U.S. Pat. No. 6,106,009, a housing 1 is formed by a cylindrical member 2 containing a circumferential wall portion 22 and a side surface portion 21 and a cup-shaped member 3 that closes the opening of the cylindrical member 2, and a cylindrical filter 51 is disposed inside the housing. At one end (on the igniter 4 side) of the housing, the outer diameter of the circumferential wall portion 22 is reduced by the inclined surface 24, and positioning is performed by abutting the inner circumferential surface of this portion of reduced diameter against an outer circumferential surface of one end of the filter 51.
U.S. Pat. No. 3,904,221 describes an aspect in which both ends of a cylinder 5 having a hole 7 are closed, and a filter 1, an igniter 3, and a gas generating agent 2 are accommodated inside the cylinder. FIG. 2 shows an aspect in which a retainer-like member with a bolt mounted on the lower side thereof is attached, both end portions in the axial direction are reduced in diameter, and the outer circumferential surface of the cylinder 5 is also disposed in the abutment state thereof.
JP-A No. 2001-239913 describes an aspect in which a filter 5, a gas generating agent 8, and an igniter 6 are disposed inside a housing 3 containing a diffuser shell 1 and a closure shell 2, and a bent portion 56, which is a boundary portion of a circumferential wall portion 55 of the closure shell 2 and a circular portion 54, abuts against a circumferential edge at the lower end of the filter 5.


A system and method for auditing telephone number records of a telecommunications company. The process may include querying at least one database managed by a telecommunications carrier to obtain first data records associated with telephone numbers owned by the telecommunications carrier. A database external from the telecommunications company may be queried to obtain second data records associated with telephone numbers owned by the telecommunications carrier. At least one parameter of the first and second data records may be compared and, a subset of data records of the first and second data records that have discrepancies with the at least one parameter may be determined. A report including the subset of data records may be generated.

The ten-digit North American Numbering Plan (NANP) currently used by the United States and 19 other countries is rapidly being depleted. Management of this resource is impaired by a lack of uniform data. Under the Communications Act of 1934, as amended by the Telecommunications Act of 1996, the Federal Communications Commission (FCC) was given "exclusive jurisdiction over those portions of the North American Numbering Plan that pertain to the United States." Pursuant to that authority, the FCC conducted a rulemaking that, among other things, addressed regular reporting on numbering resources used by United States telecommunications carriers.
The FCC appointed an agency, known as the North American Numbering Plan Administrator (NANPA), to monitor numbering resources utilized by all telecommunications carriers using the resources and to project the dates of area code and North American Numbering Plan exhaust. In their duties, NANPA created a numbering utilization report that telecommunications carriers are to submit semi-annually. The report is known as the Numbering Resource Utilization/Forecast (NRUF) Report.
The NRUF Report includes a number of different forms that provide NANPA with information as to the usage of telecommunications allotted phone numbers. As understood in the telecommunications industry, each telecommunications carrier is allotted a certain number of phone numbers in blocks of 10,000, which is generally subdivided into ten blocks of a thousand. Ten-digit phone numbers include a (i) numbering plan area (NPA) (i.e., area code), which is three digits, (i) central office code, which is also three digits, and (iii) thousands digit block (i.e., the first digit of the last four digits of a phone number). Telecommunications carriers provide phone numbers to customers from these blocks of a thousand numbers. As a thousands block is filled, it is considered to be exhausted. Some thousands digit blocks become filled while others become empty depending on how the telecommunications carrier customer base changes. The telecommunications carrier reports the existing usage and forecasts future usage of the phone numbers in the NRUF Report.
One problem that exists with the NRUF Report is the time necessary to collect and process the information to report. Telecommunications carriers generally have many divisions, many central offices, thousands of thousands digit blocks, and millions of customers. Managing this information and reporting it can take several man-weeks for producing each NRUF Report. Another problem that exists is that there is no standard method for forecasting exhaustion of a thousands digit block.
In managing telephone numbers and usage thereof, telecommunications carriers generally maintain internal databases to track existing telephone number inventory. In addition, an industry group, known as Telcordia Routing Administration (TRA), operates a local exchange routing guide (LERG) database to inventory telephone numbers owned by each telecommunications carrier. The LERG database maintains other relevant information associated with the telephone numbers, which are generally stored as data records in blocks of a thousand, commonly known as thousands blocks. The relevant information includes status of the thousands blocks, such as whether the thousands blocks are pooled or portable. A common problem in the telecommunications industry is discrepancies within and between the telecommunications carrier managed and LERG databases. Typically, these discrepancies are determined by chance while reviewing records for other purposes. Alternatively, a visual inspection of the data records for comparison purposes are performed, but such a task is time consuming and is generally low priority, so errors in the telecommunications carriers' telephone number inventory perpetuate and increase over time. These inventory errors cause phone number management problems throughout the telecommunications industry.

System and method for auditing a telephone number inventory of a telecommunications carrier


An elongated molding for a vehicle, including: a main body including, a head portion arranged at a front surface side of a circumferential edge of a window pane, a leg portion protruding from a back surface of the head portion and being arranged to face an end surface of the circumferential edge of the window pane, and a foot portion protruding from a tip of the leg portion toward a center of the window pane, wherein a volume raising portion is integrally provided to at least a portion of a back surface of the head portion in a longitudinal direction thereof, wherein a thickness of the volume raising portion varies at at least some positions in the longitudinal direction, and wherein the volume raising portion is made of a resin material softer than a resin material constituting the head portion.

Various types of window moldings made of metal, resin, etc., are known. As a window molding made of resin, which is molded by extrusion molding or injection molding, a type that is attached to a circumferential edge of a window pane by pinching the circumferential edge of the window pane from three directions of a front surface, a back surface, and an end surface of a window glass (window pane) so as to surround a circumference edge of the window pane is known. Further, in elongated moldings, there is known an isomorphic type (same cross-sectional type) in which the cross-sectional shape in a longitudinal direction is constant. However, a number of types (variant cross-sectional types) of which the cross-sectional shape in the longitudinal direction varies are also known.
Among the variant cross-sectional type resinous moldings, for example, there is a molding designed such that a height difference (h) between a front surface of a decorative portion of the molding attached to a side portion (a left side or a right side of a vehicle) of a window glass and a front surface of the window glass (window pane) becomes gradually larger in the downward direction of the window glass, from viewpoints of functionality and designability. Such moldings include moldings shown in JP-A-H03-128721 and JP-A-2003-165137. The molding of JP-A-H03-128721 is formed through extrusion molding, and is intended to be attached to an upper portion and side portions (left and right side portions) of a front window glass. The molding of JP-A-2003-165137 is formed through injection molding, and is intended to be attached to the side portions (left and right side portions) of the front window glass.

Molding for vehicle and method for manufacturing same


An apparatus for measuring a systolic blood pressure of a living subject, including an inflatable cuff which is adapted to be wound around a body portion of the subject and includes a first inflatable bag which is inflatable to press an artery of the body portion, a first amplitude determining device for determining a first amplitude of each of a plurality of heartbeat-synchronous pulses of a first pulse wave which is produced in the first inflatable bag when a pressure in the first bag is changed, a pulse-wave detecting device which detects a second pulse wave which propagates from the artery to a downstream-side portion of the cuff as seen in a blood-flow direction in which blood flows in the artery, a second amplitude determining device for determining a second amplitude of each of a plurality of heartbeat-synchronous pulses of the second pulse wave which is detected by the pulse-wave detecting device when the pressure of the first inflatable bag is changed, a ratio calculating device for calculating a ratio of one of each of the first amplitudes determined by the first amplitude determining means and each of the second amplitudes determined by the second amplitude determining means to the other of the each of the first amplitudes and the each of the second amplitudes, and a blood-pressure determining device for determining the systolic blood pressure of the subject, based on the ratios calculated by the ratio calculating device.

1. Field of the Invention
The present invention relates to an oscillometric-type blood-pressure measuring apparatus which employs, for improving the accuracy of blood-pressure measurements, a pulse-wave detecting device for detecting a pulse wave propagated to a downstream-side portion of an inflatable cuff which is wound around a body portion of a living subject, and which determines a blood pressure of the subject based on the pulse wave detected by the pulse-wave detecting device. The downstream-side portion of the cuff means the portion thereof other than the upstream-side portion thereof.
2. Related Art Statement
Generally, an oscillometric-type blood-pressure (BP) measuring apparatus includes (a) an inflatable cuff which is adapted to be wound around a body portion of a living subject and includes an inflatable bag; (b) a pressure changing device which increases a pressing pressure of the inflatable bag up to a prescribed pressure value which can completely stop the flow of blood through an artery under the cuff, and subsequently slowly decreases the pressure in the bag at a prescribed rate; a pressure sensor which continuously detects the pressure in the bag during the slow deflation of the bag; a pulse-wave filter which extracts a pulse wave from the pressure in the bag, continuously detected by the pressure sensor; and a means for determining, as a systolic blood pressure of the subject, a pressure in the bag at a rising point where respective amplitudes of successive heartbeat-synchronous pulses of the extracted pulse wave significantly greatly changes to increase.
However, the above BP measuring apparatus has the problem that since the rising point of the amplitudes of the pulse wave is indefinite, the determined systolic BP value of the subject may be inaccurate. The reason is that even if the pressing pressure of the cuff is higher than the systolic BP value of the subject, the pulsation of the artery under the cuff may start under an upstream-side portion of the cuff. In particular, in the case where the body portion around which the cuff is wound is difficult to completely stop the flow of blood in the artery thereof, the pulsation of the artery is likely to be large even if the pressing pressure of the cuff may be higher than the systolic BP value of the subject. Therefore, the rising point of the amplitudes of the pulse wave is likely to be indefinite.
To solve the above-indicated problem, it has been proposed to provide a pulse-wave detecting device on an inner side and a downstream side of an inflatable bag of an inflatable cuff and determine a BP value of a living subject based on respective amplitudes of heartbeat-synchronous pulses of a pulse wave detected by the pulse-wave detecting device. For example, the pulse-wave detecting device may be one which includes another or second inflatable bag which is independent of the first inflatable bag for pressing the artery, and is provided on the downstream side of the first bag; and a pressure sensor which detects a pressure in the second bag. A BP value of the subject is determined based on respective amplitudes of heartbeat-synchronous pulses of a pulse wave which is produced in the second bag and is detected by the pressure sensor. Even if the pulsation of the artery may occur under the upstream-side portion of the cuff when the pressing pressure of the cuff is higher than the systolic BP value of the subject, the pulsation does not directly propagate to the second inflatable bag provided in the downstream-side portion of the cuff. Therefore, a definite rising point of the amplitudes of the pulse wave can be found and accordingly an accurate systolic BP value of the subject can be determined.
However, in some cases, the rising point of the amplitudes of the pulse wave detected by the above-described pulse-wave detecting device may be indefinite. In particular, in the case where a pulse wave is detected from an ankle of a living subject, the rising point is likely to be indefinite. The reason is that although the pulse wave which occurs under the upstream-side portion of the cuff when the pressure of the cuff is higher than the systolic BP value of the subject does not directly propagate to the second inflatable bag of the pulse-wave detecting device, the pulse wave is detected by the pulse-wave detecting device via the first inflatable bag. More specifically described, the pulse wave which occurs under the upstream-side portion of the cuff when the cuff pressure is higher than the systolic BP value, causes a pressure oscillation in the first inflatable bag, which in turn is detected by the pulse-wave detecting device. Therefore, the systolic BP value determined based on the amplitudes of the pulse wave detected by the pulse-wave detecting device may be inaccurate.
It is an object of the present invention to provide a blood-pressure measuring apparatus which can measure an accurate systolic blood pressure of a living subject.
The above object has been achieved by the present invention. According to a first feature of the present invention, there is provided an apparatus for measuring a systolic blood pressure of a living subject, comprising an inflatable cuff which is adapted to be wound around a body portion of the subject and includes a first inflatable bag which is inflatable to press an artery of the body portion; a first amplitude determining means for determining a first amplitude of each of a plurality of heartbeat-synchronous pulses of a first pulse wave which is produced in the first inflatable bag when a pressure in the first bag is changed; a pulse-wave detecting device which detects a second pulse wave which propagates from the artery to a downstream-side portion of the cuff as seen in a blood-flow direction in which blood flows in the artery; a second amplitude determining means for determining a second amplitude of each of a plurality of heartbeat-synchronous pulses of the second pulse wave which is detected by the pulse-wave detecting device when the pressure of the first inflatable bag is changed; a ratio calculating means for calculating a ratio of one of each of the first amplitudes determined by the first amplitude determining means and each of the second amplitudes determined by the second amplitude determining means to the other of said each of the first amplitudes and said each of the second amplitudes; and a blood-pressure determining means for determining the systolic blood pressure of the subject, based on the ratios calculated by the ratio calculating means.
In the present BP measuring apparatus, the first amplitude determining means determines a first amplitude of each of a plurality of heartbeat-synchronous pulses of a first pulse wave which is produced in the first inflatable bag when a pressure in the first bag is changed; the second amplitude determining means determines a second amplitude of each of a plurality of heartbeat-synchronous pulses of a second pulse wave which is detected by the pulse-wave detecting device when the pressure of the first inflatable bag is changed; the ratio calculating means calculates a ratio of one of each of the first amplitudes and each of the second amplitudes to the other of the each of the first amplitudes and the each of the second amplitudes; and the BP determining means determines, based on the ratios, the systolic BP value of the subject. When the pressure of the first inflatable bag is higher than the systolic BP value of the subject, the pulse-wave detecting device including the second inflatable bag provided on the downstream side of the first inflatable bag detects the pulse wave only indirectly via the first bag. Thus, the second amplitudes are small. On the other hand, when the pressure of the first bag is not higher than the systolic BP value of the subject, the pulse-wave detecting device detects the pulse wave not only indirectly via the first bag but also directly from the artery. Thus, the second amplitudes are great. However, even if the pressure of the first bag is higher than the systolic BP value, the pressure pulse wave is directly transmitted from the artery to the first bag. Thus, the first amplitudes do not change so greatly as the second amplitude, when the pressure of the first bag is equal to the systolic BP value. Therefore, the amplitude ratios calculated by the ratio calculating means greatly changes when the pressure of the first bag is equal to the systolic BP value, and the BP determining means can determine, based on the amplitude ratios, an accurate systolic BP value of the subject.
According to a second feature of the present invention, the pulse-wave detecting device includes a second inflatable bag which is provided in the downstream-side portion of the cuff wound around the body portion of the living subject, such that the second inflatable bag is located on a downstream side of a first portion of the first inflatable bag and on an inner side of a second portion of the first bag, the second bag having, in the blood-flow direction, a width smaller than a width of the first bag, and wherein the pulse-wave detecting device detects the second pulse wave which is produced in the second bag. Since the present BP measuring apparatus enjoys a simple construction, it can be produced with ease and at low cost.
According to a third feature of the present invention, the blood-pressure determining means determines the systolic blood pressure of the subject, based on the ratios which are calculated, by the ratio calculating means, based on a portion of pre-selected ones of the first amplitudes or the second amplitudes that falls within a predetermined pressure range. Since the BP determining means determines the systolic BP value of the subject, based on the ratios calculated based on only a portion of pre-selected ones of the first amplitudes or the second amplitudes that falls within a predetermined pressure range, the BP determining means does not erroneously determine a systolic BP value in a pressure range different from the predetermined pressure range. Thus, the BP determining means can obtain a more accurate systolic BP value of the subject.
According to a fourth feature of the present invention, the blood-pressure measuring apparatus further comprises a smoothing means for smoothing the ratios calculated by the ratio calculating means, and the blood-pressure determining means determines the systolic blood pressure of the subject, based on the ratios smoothed by the smoothing means. Even if the amplitude ratios calculated by the ratio calculating means may temporarily greatly change, the smoothing means smoothes or eliminates the temporary change of the amplitude ratios, and the BP determining means determines the systolic BP vale of the subject based on the smoothed amplitude ratios. Thus, the BP determining means can obtain a more accurate systolic BP value of the subject.
According to a fifth feature of the present invention, the smoothing means smoothes the ratios which are calculated, by the ratio calculating means, based on a portion of pre-selected ones of the first amplitudes or the second amplitudes that falls within a predetermined pressure range, and the blood-pressure determining means determines the systolic blood pressure of the subject, based on the ratios smoothed by the smoothing means. Since the BP determining means determines the systolic BP value of the subject, based on the ratios calculated based on only a portion of pre-selected ones of the first amplitudes or the second amplitudes that falls within a predetermined pressure range, the BP determining means does not erroneously determine a systolic BP value based on a great change of the amplitude ratios in a pressure range different from the predetermined pressure range. In addition, even if the amplitude ratios may temporarily greatly change in a pressure range different from the predetermined pressure range, the smoothing means smoothes or eliminates the temporary change of the amplitude ratios, and the BP determining means does not determine an erroneous systolic BP vale of the subject based on the temporary change of the amplitude ratios. Thus, the BP determining means can obtain a more accurate systolic BP value of the subject.


Disclosed is a range finder system which includes a virtual image type first optical system for observing an object, and a second optical system for electronically capturing image of at least a part of the object. The range finder system is provided with an LCD (liquid crystal display) which displays the image captured by the second optical system. The image displayed on the liquid crystal display is directed to the virtual image type finder optical system, and the image as displayed on the LCD is combined with the image observed through the first optical system. Thus, two images are observed by a photographer as superimposed. A display controller controls the LCD so that the degree of coincidence of the superimposed images is varied in the direction of a base length based on an object distance information.

The present invention relates to a range finder system using superimposed two images.
Conventional range finder system is provided with, for example, a first and a second windows arranged spaced apart from each other by a predetermined base line length. Light beams entered through the first and second windows are combined by a beam combiner such as a half mirror and then directed into a common eyepiece optical system. A photographer observes the dual image, which is formed by superimposing two images respectively corresponding to the first and second windows, of an object through the eyepiece optical system. A rotatable mirror is provided between the second window and the half mirror to vary the degree of coincidence of the superimposed two images in the direction of the base line, and a distance to the object is determined based on the angle of rotation of the rotatable mirror at which the two superimposed images of the object coincide.
In an interlocking type range finder, movement of a photographing lens is interlocked with the rotation of the rotatable mirror such that the photographing lens is brought into an in-focus position when the rotation angle of the rotatable mirror is adjusted and the superimposed images coincide.
Since the above-described range finder requires an optical path running from the first window to the eyepiece, and another optical path running from the second window to the half mirror and then to the eyepiece, a relatively large space is required which prevents cameras from being made compact. Further, in order to improve measurement accuracy in range finding, the base length needs to be sufficiently long, and a space for accommodating the optical path between the first and second windows becomes large.


The present invention provides a multi-coil inductive power transfer primary comprising a plurality of coil. A power transfer regime is selected based on a determined load on each of the plurality of coils.

IPT systems, and the use of a pad which includes one or more windings which may comprise the primary or secondary windings for inductive power transfer, are reproduced in our International Patent Publication No. WO 2008/14033, the contents of which are incorporated herein by reference.
One particular example application of IPT power transfer pads is electric vehicle charging, and that application is discussed in this section to provide the background to one application of the invention. However, electric vehicle charging is an example of only one application, and the invention has application to inductive power transfer in general. Electric vehicle charging may occur while the vehicle is stationary, or alternatively while the vehicle is moving along a roadway, for example. IPT power transfer pads can be used both in the vehicle as a power "pickup" (i.e. the secondary side winding of the IPT system), and at a stationary location such as a garage floor or a roadway for example as the "charging pad" (i.e. the primary side winding) from which power is sourced.
The purpose of an IPT roadway system is to wirelessly transfer power to a stationary or moving vehicle without physical contact to the vehicle. The transmitting part of the system consists of a power supply supplying a lumped coil (for example a pad as described above) or a track with many similar lumped coils where such a system is tuned for operation at a suitable frequency, usually anywhere from 10 kHz to 150 kHz. Where the receiver is placed underneath a vehicle and coupled to receive power either when the vehicle is stationary above or near (in sufficiently close proximity to couple power) to the primary transmitter. The pickup receiver also typically comprises a lumped coil (such as a pad described above) which is connected to a converter and appropriate controller within the vehicle to regulate power. For convenience, the part of a roadway from which power may be received inductively is referred to herein as a track.
The track may be formed by placing a plurality of pads along the centre of a lane in a roadway. This results in the possibility of an essentially continuous supply of power to the vehicle as it moves along the roadway in the immediate vicinity of the track.
In recent years such systems have received increasing attention due to their potential to allow sustainable wireless powered personal transportation. For such a system to be useful it should not only be able to transfer sufficient power over an airgap of reasonable size (e.g. 100-300 mm) it should also prove tolerant to any displacements between track and pickup, to avoid dependency on a vehicle-to-track guidance system. In a roadway system such displacement will most likely occur in the lateral direction (orthogonal to both vertical and the direction of movement) for moving vehicles. For stationary vehicle charging the ability to transfer acceptable levels of power with suitable longitudinal displacement is of particular concern in order to ensure ease of parking. The power transfer profile in the pick-up pad is ideally a smooth power profile which is essentially constant (and sufficient) over as wide as possible a distance laterally, with smooth drop-offs at each end. Such a power transfer profile eases the demands on the electronic (primary and secondary) regulators in the system, enabling improved operating performance for a comparable coupling over a system where during operation significant variations are experienced in the coupling between the primary and receiver pads.
A further problem to be solved is the need to be able to couple to vehicles or appliances with varying ground clearances, which largely determines the distance between the charging pad on the ground or as part of a primary structure (such as a mat or other surface) and the secondary pad of a particular vehicle or other device. In such applications there will be significant changes in coupling between the two pads that may require the primary inductive apparatus to operate with substantially increased VA to meet the power demand. This operation will also increase the magnetic field leakage present in the system, which may exceed allowable limits defined by regulations.
A further problem may occur if the primary and secondary inductive pads are polarised but oriented at an angle of 90 degrees to each other such that there is no coupling, and thus no possibility of power transfer.
Yet a further problem arises due to the many different possible pad designs and operation methods, and the potential mismatch between the charging and pickup pads. For example, the pad on the ground may have a completely different structure to the vehicle pickup, and/or may be operated as a single phase, two phase or multiphase system to produce substantially different field flux shapes within the space between the two coupled pads under time varying conditions. Under such conditions the ability of a fixed magnetic structure to capture power is limited.
An inductive power transfer apparatus which goes at least some way to addressing some of the above problems was described in our International Patent Publication No. WO 2011/16737, the contents of which are incorporated herein by reference. Embodiments of WO 2011/16737 provide a magnetic flux pad for generating or receiving magnetic flux, the pad including a magnetically permeable core, two substantially flat overlapping coils magnetically associated with the core whereby there is substantially no mutual coupling between the coils.


The toner is a low-environmental load toner for electrostatic image development. The toner includes toner particles containing a resin. The resin contains a vinyl polymer having a structural unit represented by the following general formula (1). In the formula, R1 to R5 are each a hydrogen atom, an alkoxy group having 1 to 4 carbon atoms or —OCOR6 (R6 is an alkyl group having 1 to 8 carbon atoms), at least two of R1 to R5 are hydrogen atoms, and at least one thereof is an alkoxy group having 1 to 4 carbon atoms or —OCOR6.

1. Field of the Invention
The present invention relates to a toner for electrostatic image development that is used in image formation of an electrophotographic system (which hereinafter may be simply referred to as a "toner").
2. Description of the Related Art
Laws such as the "Law Concerning the Promotion of Procurement of Eco-Friendly Goods and Services by the State and other Entities (Law on Promoting Green Purchasing)" have been enforced, and it is contemplated to use raw materials other than those derived from petroleum. In image formation of an electrophotographic system, for example, there is a demand for the use of low environmental load toners such as a toner containing, as a binder resin, biomass plastic obtained from a raw material derived from an organic resource other than fossil resources.
Examples of the raw material derived from an organic resource other than such fossil resources include those disclosed in Patent Literatures 1 and 2.

Toner for electrostatic image development

KONICA MINOLTA BUSINESS TECHNOLOGIES, INC.


The present invention relates to a geo-positional treading sphere (10) having a sphere (12) rotatably cradled within a base (14). The base (14) has at least one base pylon (14A) having a base pylon driver to rotate the sphere (12) longitudinally and/or latidudinally in response to an instant position which the user (16) is located within the sphere (12). The base (14) has a plurality of base bearings (14D) attached thereto which function to facilitate the sphere's (12) rotation. The user (16) adorns a user control (18) consisting of a user control backpack (18A) and a user control helmet (18B). The user control backpack (18A) has at least one user control backpack infrared distance sensor to send and receive signals to the inner wall of the sphere (12). The received signals by the at least one user control backpack infrared distance sensor is relayed to the geo-positional treading sphere operating system (110). The received signals by the at least one user control helmet beam is relayed to the geo-positional treading sphere operating system (110). The geo-positional treading sphere operating system (110) controls rotation of the sphere (12) in relation to the position of the user (16) therein.

1. Field of the Invention
The present invention relates to virtual reality apparatus. More particularly, the present invention relates to virtual reality apparatus having a geo-positional treading sphere and geo-positional treading sphere operating system.
2. Description of the Prior Art
During the last decade, virtual reality devices have increased in popularity. The prior virtual reality devices were solely head gear (helmet) and hand controls. Recently, configurations of equipment within which a user is positioned during the virtual reality experience have been devised. However, these configurations of equipment have been limited in movement to up, down and sideways movement. The present invention combines virtual reality with three-dimensional 3D geo-positional treading sphere operating system with functions to rotate a geo-positional treading sphere in both a longitudinal and latitudinal direction in response to movement of the user therein.
Numerous innovations for virtual reality devices have been provided in the prior art that are adapted to be used. Even though these innovations may be suitable for the specific individual purposes to which they address, they would not be suitable for the purposes of the present invention as heretofore described.

Geo-positional treading sphere and geo-positional treading sphere operating system


A method is provided for processing and printing print job portions. The method includes providing an output related attribute, and using the attribute to divide a portion of one or more print jobs into a first section (including a first print output stack) and a second section (including a second print output stack). When the portion of the one or more print jobs is printed, an output stack processing instruction is used to separate the first output stack from the second print output stack along a boundary defined by the instruction.

The disclosed embodiments relate generally to a method for processing and printing print job portions and, more particularly, to an approach in which print output stacks are separated during printing by reference to an output related attribute, such as an output related attribute for at least one offline finishing device.
Creation and production of printed documents often involves many production and finishing operations that are highly variable with each job. In general, the various operations can be grouped into three major phases: 1) creation of the document information, including prepress operations that render the document in a form suitable for printing, 2) printing of the information onto some form of media such as paper, and 3) finishing of the selected media into a completed document. These 3 major phases often have many sub-phases, and the entire process may vary from relatively simple to extremely complex.
U.S. Pat. No. 6,462,756 B1 to Hansen et al. discloses a system and method for managing production printing workflow. The system includes workflow management software for managing and facilitating the procedural stages of the workflow including job origination, job preparation, job submission and job fulfillment. The workflow management software provides an integrated object oriented interface which visually reflects and interacts with the workflow. The software further provides functionality for efficient page level modifications to documents at the job preparation stage. This functionality allows such modifications to be easily made to selected pages and visually verified by displaying visual representations of the modifications on visual representations of the pages.
U.S. Pat. No. 7,092,963 B2 to Ryan et al. discloses a print production and finishing system for electronic management and control of a wide range of finishing processes characterized by input from multiple production operations and equipment that, depending upon the job, might be variably applied to work pieces that themselves are highly variable between different jobs. The disclosed embodiments of the '963 patent are applicable to many operations where processes for production of work pieces are managed separately from processes for finishing and packaging of such work pieces.
The pertinent portions of all of the above-mentioned patents are incorporated herein by reference.
Traditionally, when a document is composed, the person doing the composition will create one or more electronic image files that represent the parts of the document to be produced. These electronic image data files may be stored in many different formats by many different document creation and manipulation programs. For instance, for a complex document such as a book that utilizes color printing for book covers and pictorial inserts, any of a variety of Page Description Languages (PDLs), such as Postscript® and Postscript-compatible languages, may be used to render the color images in printable form. Often different components within a document will utilize different PDLs. For instance, the cover may be created by a different work team or upon different equipment than photographic reprints or other internal color components. Each prepress team or prepress device may utilize a PDL optimized for its use. For pages comprised of simple monochrome text, desk-top publishing programs may be utilized to render such pages or a simpler word processing language may be utilized. Still other prepress formats may be utilized for printing of inserts, dividers, and other possible components internal to the finished document. There also may be included in the assembly/finishing job non-printed components such as, without limitation, plastic separators, previously printed sheets retrieved from inventory, photographically produced sheets, or specialized media such as vinyl disk holders or perfume sample packs.
Workflows of the type described in the U.S. Pat. No. 6,462,756 are typically well suited for handling normal sized jobs of definite length, but not necessarily jobs of "indefinite length." Indefinite length jobs are jobs so large that no component in the workflow is generally capable of handling the entire job. An example of an indefinite length job is a variable data job that can run into the tens or even hundreds of thousands of individual variable information ("VI") records. An indefinite length VI can be challenging to execute because oftentimes the original input PDL VI record order must be maintained from PDL generation, through production to shipping.
The challenge associated with executing an indefinite length job can be further compounded when it becomes necessary to use imposition. In one approach, an indefinite length job is imposed in what is referred to as cut & stack, cut & marry, z-sort, or zip sort imposition. This imposition flows the original document pages vertically though a printed stack one multi-up position at a time. This permits the printed stack to be cut into multiple stacks that can then be combined to recreate the original document. Cut & stack imposition finds use in the printing of credit card statements where the statements of many customers may be printed together as one large job.
Execution of indefinite length jobs can become particularly problematic when the printed stack is larger than the output capacity of the stacker, as is often the case when printing an indefinite length job. For those instances in which the original document pages flow vertically through the entire printed stack, the document cannot be finished until all pages of the imposed document are printed. Execution of certain indefinite length jobs (e.g. a 500,000 page credit card statement run), can result in document stacks that cannot realistically be sent to a bindery for finishing.
To alleviate the problem resulting from oversized document stacks, imposition applications may set a "stack depth" parameter that sets a maximum number of sheets through which contiguous input document pages may be vertically flowed. Smaller stacks containing a contiguous portion of the original input document result so that a cut & stack process can be employed without waiting for the entire job to finish printing. Although this enhancement of setting stack height can mean the difference between imposing or not imposing a given indefinite length job, it still does not necessarily result in efficient finishing of infinite length jobs.
It would be desirable to provide an enhancement for handling infinite length jobs in such a way as to enable better parallelism in finishing the resulting output. In particular, such enhancement might include evaluating constraints from business rules and finishing devices to determine an optimal approach for flowing a document though imposition so that portions of the infinite length job could be processed in a variety of finishing operations without losing confidence in the ability to reconstitute the original input document.
In accordance with a first aspect with the disclosed embodiments there is disclosed a method of processing and printing print job portions, comprising: (A) providing an output related attribute for at least one offline finishing device, the output related attribute for the at least one finishing device corresponding with a first print output stack height; (B) dividing at least a portion of one or more print jobs, with the first print output stack height, into a first section including a first set of pages and a second section including a second set of pages, wherein the first section corresponds with a first print output stack having a second print output stack height and the second section corresponds with a second print output stack having a third print output stack height; (C) providing a print output stack processing instruction to define a boundary between the first section and the second section; (D) printing the portion of the one or more print jobs to output the first and second print output stacks; and (E) during said output of (D), separating the first print output stack from the second print output stack with the output stack processing instruction.
In accordance with a second aspect of the disclosed embodiments there is disclosed a method of processing and printing print job portions, comprising: (A) providing an output related attribute; (B) dividing at least a portion of the one or more print jobs, with the output related attribute, into a first set of information corresponding with a first set of pages and a second set of information corresponding with a second set of pages, wherein the first set of pages corresponds with a first print output stack having a first print output stack height and the second set of information corresponds with a second print output stack having a second print output stack height; (C) providing a print output stack processing instruction to define a boundary between the first section and the second section; (D) printing the portion of the one or more print jobs to output the first and second print output stacks; and (E) during said output of (D), separating the first print output stack from the second print output stack with the output stack processing instruction.

Method of processing and printing print job portions for enabling bindery efficiencies