• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.271-288
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• 2002

Authors investigated the pathogenesis and treatment of dennatosurgical diseases in the ImJeungJiNamUiAn(臨證指南醫案). 1. The symptoms and diseases of dermatosurgery were as follows; 1) BanSaJinRa(반사진라) : eczema, atopic dermatitis, seborrheic dermatitis, psoriasis, lichen planus, pityriasis rosea, hives, dermographism, angioedema, cholinergic urticaria, urticaria pigmentosa, acne, milium, syringoma, keratosis pilaris, discoid lupus erythematosus, hypersensitivity vasculitis, drug eruption, polymorphic light eruption, rheumatic fever, juvenile rheumatoid arthritis(Still's disease), acute febrile neutrophilic dermatosis(Sweet's syndrome), Paget's disease, folliculitis, viral exanthems, molluscum contagiosum, tinea, tinea versicolor, lymphoma, lymphadenitis, lymphangitis, granuloma annulare, cherry angioma 2) ChangYang(瘡瘍) : acute stage eczema, seborrheic dermatitis, stasis ulcer, intertrigo, xerosis, psoriasis, lichen planus, ichthyosis, pityriasis rosea, rosacea, acne, keratosis pilaris, dyshidrosis, dermatitis herpetiformis, herpes gestationis, bullae in diabetics, pemphigus, lupus erythematosus, fixed drug eruption, erythema multiforme, toxic epidermal necrolysis, toxic shock syndrome, staphylococcal scaled skin syndrome, scarlet fever, folliculitis, impetigo, pyoderma gangrenosum, tinea, candidiasis, scabies, herpes simplex, herpes zoster, chicken pox, Kawasaki syndrome, lipoma, goiter, thyroid nodule, thyroiditis, hyperthyroidism, thyroid cancer, benign breast disorder, breast carcinoma, hepatic abscess, appendicitis, hemorrhoid 3) Yeok(疫) : scarlet fever, chicken pox, measles, rubella, exanthem subitum, erythema infectiosum, Epstein-Barr virus infection, cytomegalovirus infection, hand-foot-mouth disease, Kawasaki disease 4) Han(汗) : hyperhidrosis 2. The pathogenesis and treatment of dermatosurgery were as follows; 1) When the pathogenesis of BalSa(발사), BalJin(發疹), BalLa(발라) and HangJong(項腫) are wind-warm(風溫), exogenous cold with endogenous heat(外寒內熱), wind-damp(風濕), the treatment of evaporation(解表) with Menthae Herba(薄荷), Arctii Fructus(牛蒡子), Forsythiae Fructus(連翹) Mori Cortex(桑白皮), Fritillariae Cirrhosae Bulbus(貝母), Armeniaoae Amarum Semen(杏仁), Ephedrae Herba(麻黃), Cinnamomi Ramulus(桂枝), Curcumae Longae Rhizoma(薑黃), etc can be applied. 2) When the pathogenesis of BuYang(부양), ChangI(瘡痍) and ChangJilGaeSeon(瘡疾疥癬) are wind-heat(風熱), blood fever with wind transformation(血熱風動), wind-damp(風濕), the treatment of wind-dispelling(疏風) with Arctii Fructus(牛蒡子), Schizonepetae Herba(荊芥), Ledebouriellae Radix(防風), Dictamni Radicis Cortex(白鮮皮), Bombyx Batrytioatus(白？?), etc can be applied. 3) When the pathogenesis of SaHuHaeSu(사후해수), SaJin(사진), BalJin(發疹), EunJin(은진) and BuYang(부양) are wind-heat(風熱), exogenous cold with endogenous heat(外寒內熱), exogenous warm pathogen with endogenous damp-heat(溫邪外感 濕熱內蘊), warm pathogen's penetration(溫邪內陷), insidious heat's penetration of pericardium(伏熱入包絡), the treatment of Ki-cooling(淸氣) with TongSeongHwan(通聖丸), Praeparatum(豆？), Phyllostachys Folium(竹葉), Mori Cortex(桑白皮), Tetrapanacis Medulla(通草), etc can be applied. 4) When the pathogenesis of JeokBan(적반), BalLa(발라), GuChang(久瘡), GyeolHaek(結核), DamHaek(痰核), Yeong(？), YuJu(流注), Breast Diseases(乳房疾患) and DoHan(盜汗) are stagnancy's injury of Ki and blood(鬱傷氣血), gallbladder fire with stomach damp(膽火胃濕), deficiency of Yin in stomach with Kwolum's check (胃陰虛 厥陰乘), heat's penetration of blood collaterals with disharmony of liver and stomach(熱入血絡 肝胃不和), insidious pathogen in Kwolum(邪伏厥陰), the treatment of mediation(和解) with Prunellae Spica(夏枯草), Chrysanthemi Flos(菊花), Mori Folium (桑葉), Bupleuri Radix(柴胡), Coptidis Rhizoma(黃連), Scutellariae Radix(黃芩), Gardeniae Fructus(梔子), Cyperi Rhizoma(香附子), Toosendan Fructus(川？子), Curcumae Radix(鬱金), Moutan Cortex(牧丹皮), Paeoniae Radix Rubra(赤芍藥), Unoariae Ramulus Et Uncus(釣鉤藤), Cinnamorni Ramulus(桂枝), Paeoniae Radix Alba(白芍藥), Polygoni Multiflori Radix (何首烏), Cannabis Fructus (胡麻子), Ostreae Concha(牡蠣), Zizyphi Spinosae Semen(酸棗仁), Pinelliae Rhizoma(半夏), Poria(백복령). etc can be applied. 5) When the pathogenesis of BanJin(반진), BalLa(발라), ChangI(瘡痍), NamgChang(膿瘡). ChangJilGaeSeon(瘡疾疥癬), ChangYang(瘡瘍), SeoYang(署瘍), NongYang(膿瘍) and GweYang(潰瘍) are wind-damp(風濕), summer heat-damp(暑濕), damp-warm(濕溫), downward flow of damp-heat(濕熱下垂), damp-heat with phlegm transformation(濕熱化痰), gallbladder fire with stomach damp(膽火胃濕), overdose of cold herbs(寒凉之樂 過服), the treatment of damp-resolving(化濕) with Pinelliae Rhizoma(半夏), armeniacae Amarum Semen(杏仁), Arecae Pericarpium(大腹皮), Poria(백복령), Coicis Semen(薏苡仁), Talcum(滑石), Glauberitum(寒水石), Dioscoreae Tokoro Rhizoma(？？), Alismatis Rhizoma(澤瀉), Phellodendri Cortex(黃柏), Phaseoli Radiati Semen(？豆皮), Bombycis Excrementum(?沙), Bombyx Batryticatus(白？?), Stephaniae Tetrandrae Radix(防己), etc can be applied. 6) When the pathogenesis of ChangPo(瘡泡), hepatic abscess(肝癰) and appendicitis(腸癰) are food poisoning(食物中毒), Ki obstruction & blood stasis in the interior(기비혈어재과), damp-heat stagnation with six Bu organs suspension(濕熱結聚 六腑不通), the treatment of purgation(通下) with DaeHwangMokDanPiTang(大黃牧丹皮湯), Manitis Squama(穿山甲), Curcumae Radix(鬱金), Curcumae Longae Rhizoma(薑黃), Tetrapanacis Medulla(通草), etc can be applied. 7) When the pathogenesis of JeokBan(적반), BanJin(반진), EunJin(은진). BuYang(부양), ChangI(瘡痍), ChangPo(瘡泡), GuChang(久瘡), NongYang(膿瘍), GweYang(潰瘍), Jeong(정), Jeol(癤), YeokRyeo(疫？) and YeokRyeolpDan(疫？入？) are wind-heat stagnation(風熱久未解), blood fever in Yangmyong(陽明血熱), blood fever with transformation(血熱風動), heat's penetration of blood collaterals(熱入血絡). fever in blood(血分有熱), insidious heat in triple energizer(三焦伏熱), pathogen's penetration of pericardium(心包受邪), deficiency of Yong(營虛), epidemic pathogen(感受穢濁), the treatment of Yong & blood-cooling(淸營凉血) with SeoGakJiHwangTang(犀角地黃湯), Scrophulariae Radix(玄參), Salviae Miltiorrhizae Radix(丹參), Angelicae Gigantis Radix(當歸), Polygoni Multiflori Radix(何首烏), Cannabis Fructus(胡麻子), Biotae Semen(柏子仁), Liriopis Tuber(麥門冬), Phaseoli Semen(赤豆皮), Forsythiae Fructus(連翹), SaJin(사진), YangDok(瘍毒) and YeokRyeoIpDan(역려입단) are insidious heat's penetration of pericardium(伏熱入包絡), damp-warm's penetration of blood collaterals(濕溫入血絡), epidemic pathogen's penetration of pericardium(심포감수역려), the treatment of resuscitation(開竅) with JiBoDan(至寶丹), UHwangHwan(牛黃丸), Forsythiae Fructus(連翹), Curcumae Radix(鬱金), Tetrapanacis Medulla(通草), Acori Graminei Rhizoma(石菖蒲), etc can be applied. 9) When the pathogenesis of SaHuSinTong(사후신통), SaHuYeolBuJi(사후열부지), ChangI(瘡痍), YangSon(瘍損) and DoHan(盜汗) are deficiency of Yin in Yangmyong stomach(陽明胃陰虛), deficiency of Yin(陰虛), the treatment of Yin-replenishing(滋陰) with MaekMunDongTang(麥門冬湯), GyeongOkGo(瓊玉膏), Schizandrae Fructus(五味子), Adenophorae Radix(沙參), Lycii Radicis Cortex (地骨皮), Polygonati Odorati Rhizoma(玉竹), Dindrobii Herba(石斛), Paeoniae Radix Alba(白芍藥), Ligustri Lucidi Fructus (女貞子), etc can be applied. 10) When the pathogenesis of RuYang(漏瘍) is endogenous wind in Yang collaterals(陽絡內風), the treatment of endogenous wind-calming(息風) with Mume Fructus(烏梅), Paeoniae Radix Alba (白芍藥), etc be applied. 11) When the pathogenesis of GuChang(久瘡), GweYang(潰瘍), RuYang(漏瘍), ChiChang(痔瘡), JaHan(自汗) and OSimHan(五心汗) are consumption of stomach(胃損), consumption of Ki & blood(氣血耗盡), overexertion of heart vitality(勞傷心神), deficiency of Yong(營虛), deficiency of Wi(衛虛), deficiency of Yang(陽虛), the treatment of Yang-restoring & exhaustion-arresting(回陽固脫) with RijungTang(理中湯), jinMuTang(眞武湯), SaengMaekSaGunjaTang(生脈四君子湯), Astragali Radix (황기), Ledebouriellae Radix(防風), Cinnamomi Ramulus(桂枝), Angelicae Gigantis Radix(當歸), Ostreae Concha(牡蠣), Zanthoxyli Fructus(川椒), Cuscutae Semen(兎絲子), etc can be applied.

• Journal of Nutrition and Health
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• v.54 no.2
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• pp.224-237
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• 2021

Purpose: Paeonia Radix Alba is a traditional herbal medicine used to treat the liver and the spleen. Many studies have reported that Paeonia Radix Alba extract (PR) affects liver injury, but there has been no study on liver injuries induced by thioacetamide (TAA). Therefore, we aimed at evaluating the effect of PR on a TAA-induced acute liver injury (ALI) model. Methods: The antioxidant activity of PR was assayed by the content of total polyphenol, total flavonoid, 1,1-diphenyl-2'-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonicacid) (ABTS) radical scavenging activities in vitro test. ALI was induced via-intraperitoneal injection of TAA (200 mg/kg body weight) for three consecutive days. Also, silymarin (100 mg/kg body weight) and PR (100 or 200 mg/kg body weight) were administered at 1 hours 30 minutes prior to TAA treatment. The levels of ammonia, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were analyzed using an assay kit. The expressions of antioxidant proteins including Nrf2, Keap1, HO-1, SOD, catalase, and GPx-1/2 and oxidative stress-related proteins including NOX2, p47^phox, and p22^phox were evaluated by the western blot analysis. Results: PR showed excellent antioxidant activity in vitro. TAA administration increased the levels of ammonia, GOT, and GPT in the ALI control group compared to the normal group, whereas it was significantly reduced by PR pretreatment. Moreover, NADPH oxidase protein expressions were upregulated after TAA treatment, while the elevated expressions were inhibited by PR pretreatment. The expressions of antioxidant protein were downregulated in the ALI control group, whereas Nrf2 activation in the PR group was accompanied by increased levels of antioxidant enzymes. Conclusion: PR administration increased the antioxidant enzymes via activation of the Keap1/Nrf2 pathway and inhibited the protein levels of NADPH oxidase factors. Taken together, these results showed that PR treatment may be considered to ameliorate acute liver injury induced by TAA.

• Korean Journal of Oriental Medicine
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• v.11 no.2
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• pp.141-154
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• 2005

The following is a taxonomic list of the specific features of external and internal shape and pattern analysis of Paeonia lactiflora PALL. and P. obovata MAX as the standard of herbal medicine. 1. External shape of original plant P. lactiflora has lancelate and elliptical leaves with no hair on both sides. It bears a flower bud at the shoot apex or leaf axil. On the other hand, P. obovata has obovate leaves with hair on the back side. It has a single flower bud at the shoot apex. 2. Physical characteristics of herbal states P. lactiflora has a bright and smooth external surface whose color is light red brown, light gray on its section and it is not easy to cut. On the other hand, P. obovata has a coarse external surface whose color is dark brown, pinkish on its section and it is easy to cut. 3. Physical characteristics of herbal state in currents Paeonia Radix Alba is brown on the external surface, and whitish on its section. On the other hand, Paeonia Radix Rubra is dark brown on the external surface, and yellowish-white on its section. 4. Internal characteristics Internal shape is correspond to that of Paeonia Radix described in literatures. Only P. lactoflora has a concentrated vascular bundle toward centeral cylinder. On the other hand, P. obovata has a scattered vascular bundle at the cortex. 5. Physicochemical pattern by HPLC Both P. lactoflora and P. obovata showed the same pattern. Paeoniforin, a main component, appears upon 13.68 in retention time (Rt) in both. In addition, both contain a large amount of paeoniflorin. Such results will, in the future, be used as basic source for the additional research, such as biological reactions and genetic discrimination.

• The Journal of Pediatrics of Korean Medicine
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• v.33 no.2
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• pp.32-47
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• 2019

Objectives The purpose of this study is to investigate clinical studies on the effectiveness of Traditional Chinese Medicine treatment on growing pains in China, and to seek better methods to treat and study for growing pains in South Korea. Methods The clinical studies from the China Academic Journal (CAJ) in China National Knowledge Infrastructure (CNKI) that were published up to January 2019 were reviewed. The key word used were '生長痛', '發育期痛', '治療', '中?治療', '中藥'. Then, the literature were analyzed in regards to the treatment methods and results. Results Among the 35 searched studies, 1 randomized controlled trials, 16 case series, and 3 case reports were selected and analyzed. In most of the studies, the effectiveness of Traditional Chinese Medicine treatment on growing pains was significantly positive. The most commonly used herbs for oral administration were Glycyrrhizae Radix et Rhizoma (甘草), Achyranthis Bidentatae Radix (牛膝), Paeoniae Radix Alba (白芍藥), Dioscoreae Rhizoma (山藥), Angelicae Gigantis Radix (當歸), Astragali Radix (黃?), Atractylodis Rhizoma Alba (白朮), Poria Sclerotium (茯?) Rehmanniae Radix Preparata (熟地黃), Lycopodii Herba (伸筋草). Other treatment methods such as, external application of herb medicine, massage, acupuncture were also used to treat growing pains. Conclusion Based on the results of the clinical studies from China, the use of chinese medicine for treatment of growing pains has been shown to be effective. Additional clinical studies are needed to confirm these findings.

• Herbal Formula Science
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• v.21 no.2
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• pp.90-99
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• 2013

Objectives : This study was carried out to investigate the traditional diet therapies for the period of postpartum recovery and lactation and to develop modern postpartum recovery foods. Korean traditional medical treatment for postpartum care focused on treating postpartum obesity, edema, agalactia was studied. Methods : We investigated the documents recorded in the medical classics of "Hyangyakjipseongbang(鄕藥集 成方)", "Donguibogam(東醫寶鑑)" and "Bangyakhappyeon(方藥合編)" published in 1433, 1613 and 1885 respectively in the Joseon Dynasty. Results : First, Radix Angelicae Sinensis was most frequently used to treat the postpartum obesity, and a lot of nourishing herbs including Radix Paeoniae Alba, Radix Astragali, Radix Ginseng, Rhizoma Chuanxiong were also used. Second, Radix Glycyrrhizae, Rhizoma Atractylodis Macrocephalase, Pericarpium Citri Reticulatae, Rhizoma Zingiberis Recens were used to treat the postpartum edema. Third, Radix Rhapontici, Medulla Tetrapanacis, Fructus Trichosanthis etc. were used to treat the postpartum agalactia. Conclusions : Consequently, we hope this study on the prescriptions and herbs for gynecology in "Hyangyakjipseongbang(鄕藥集成方)", "Donguibogam(東醫寶鑑)" and "Bangyakhappyeon(方藥合編)" will provide knowledge for diet therapy model development of postpartum care of the modern times.

• Korean Journal of Pharmacognosy
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• v.13 no.2
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• pp.79-86
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• 1982

In order to investigate pharmacological actions of combined preparations of crude drugs, 'Jakyakgamcho-Tang' were studied. The 'Jakyakgamcho-Tang' using abdominal pain and convulsion of pediatric diseases are composed of Glycyrrhizae Radix and Paeoniae Radix alba. This study was undertaken to investigate the effect of 'Jakyakgamcho-Tang'(S-I) and parched 'Jakyakgamcho-Tang'(S-II) on anticonvulsive, analgesic, antipyretic and sedative actions. The results of this study were summarized as follows; Both 'Jakyakgamcho-Tang' and parched 'Jakyakgamcho-Tang' showed anticonvulsive effects against convulsions induced by strychnine, picrotoxine and caffeine. 'Jakyakgamcho-Tang' and parched 'Jakyakgamcho-Tang' also showed analgesic and antipyretic effects. Parched 'Jakyakgamcho-Tang' only prolonged the duration of hypnosis induced by sodium pentobarbital.

• Korean Journal of Food Science and Technology
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• v.53 no.5
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• pp.544-552
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• 2021

This study investigated the anti-fibrotic and antioxidant effects of Paeonia Radix Alba water extract (PR) on thioacetamide (TAA)-induced liver fibrosis in a mouse model and its underlying mechanisms. Liver fibrosis was induced by intraperitoneal injection of TAA (three times a week) for 8 weeks. Furthermore, silymarin (50 mg/kg body weight) and PR (200 mg/kg body weight) were administered for 8 weeks. PR treatment downregulated aspartate aminotransferase (AST), alanine aminotransferase (ALT), ammonia, and myeloperoxidase levels. Moreover, PR treatment downregulated NOX2 and p47phox and upregulated antioxidant enzymes by activating the Nrf2/Keap1 signaling pathway. Furthermore, PR inhibited the factors associated with fibrosis, such as α-SMA and collagen I. AMPK/SIRT1 was upregulated by PR treatment. Overall, these results suggest that PR attenuates liver fibrosis by regulating the Nrf2/Keap1 and AMPK/SIRT1/NF-κB signaling pathways through the inhibition of oxidative stress. Hence, PR has potential as a remedy for preventing and treating liver fibrosis.

• The Journal of Internal Korean Medicine
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• v.44 no.4
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• pp.621-634
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• 2023

Objectives: This study summarizes current trends and results in clinical studies on herbal medicine treatments for chronic pancreatitis. Methods: Studies published from 2014 to 2023 were searched for on the China National Knowledge Infrastructure (CNKI), PubMed, and KMbase using the keywords "chronic pancreatitis", "herbal medicine", "herb", "만성 췌장염", and "한약". The studies were analyzed according to year, study design, characteristics of the patients, and traditional Chinese medicine (TCM) intervention. Results: In total, 23 studies were selected. There were 21 randomized controlled trials and 2 case-control studies. The most common herbal prescriptions were Qingyi-tang (淸胰湯), Radix Bupleuri (柴胡), Radix Paeoniae Alba (白芍藥), Radix Glycyrrhizae (甘草), Radix Scutellariae (黃芩), and Rhei Rhizoma (大黃). In all the studies, herbal medicine treatments were effective in the treatment of chronic pancreatitis, and efficacy was assessed using clinical symptoms, physicochemical examination, radiological examination, and relapse. Conclusions: Herbal medicine treatment can be an effective treatment for chronic pancreatitis and has potential in clinical practice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.499-506
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• 2002

Two of the essential processes required for metastasis are neoangiogenesis and tumor cell invasion of basement membranes (BM) and extracellular matrix (ECM). Recently, data showed that herbs removing blood stasis has an anti-angiogenic effects. Tonifying vital Qi and eliminating pathogenic factor was a basic modality in Oriental oncology. In this study, we investigated several Qi and Blood tonics for potent angiogenic inhibitors. Methanol extracts of samples inhibited the proliferation of ECV-304 at the concentration of 100 ㎍/㎖. Zizyphi Fructus, Glycyrrhizae Radix, Angelicae Gigantis Radix decreased the gelatinolytic activity of MMP-9 from ECV-3Q4, at the concentration of 100 ㎍/㎖ in gelatin zymography. In in vitro invasion assay, herbs inhibited the invasion activity of ECV-304 by 53% of control (Ginseng Radix), 39% (Zizyphi Fructus), 36% (Angelicae Gigantis Radix), 25% (Glycyrrhizae Radix). Ginseng Radix inhibited the capillary-like tube formation of ECV-304 at the concentration of 160 ㎍/㎖, Angelicae Gigantis Radix and Paeoniae Radix Alba inhibited at the concentration of 320 ㎍/㎖. These results indicated that Ginseng Radix, Glycyrrhizae Radix, and Angelicae Gigantis Radix could be considered as potent angiogenic inhibitiors.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1365-1380
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• 2007

Based on the theories and clinical data of oriental medicine, traditional medicinal prescriptions known to be effective to diabetic nephropathy were collected. The prescriptions were carefully examined and analyzed in order to be used as fundamental material for experiments and in clinicals. More than 40 publications related to diabetes were arranged and analyzed. Of the complications, diabetic nephropathy part of the publications were specifically focused during analysis. Data were analyzed and classified according to the quantity, prescription, differentiation of symptoms, signs and addition and subtraction of each medicine. Frequently used medicines were statistically analyzed. The most frequently used prescription was Yukmigihwang-tang(六味地黃湯) based medicine and prescriptions of its addition and subtraction, which was 15% of the total prescriptions cited. The most frequently used medicine was Astragali Radix, mentioned 192 times in the prescriptions. Hoelen was next with 180 citations, followed by Dioscoreae Rhizoma with 147 times, Rehmanniae Radix with 140, Corni Fructus with 131, Salviae Miltiorrhizae Radix with 106, Angelicae Gigantis Radix with 101, Alismatis Rhizoma with 95, Rhei Rhizoma with 90, Atractylodis Rhizoma Alba with 84, Rehmanniae Radix Preparata with 78, Leonuri Herba with 74, Moutan Cortex Radicis with 66, Aconiti Lateralis Preparata Radix with 66 Cnidii Rhizoma with 65, Pseudostellaria heterophylla with 62, Liriopis Tuber with 55, Lycii Fructus with 52, Rhei Rhizoma with 49, Codonopsis Pilosulae Radix with 44, Paeoniae Radix Rubra with 44, Schisandrae Fructus with 42, Polyporus with 42, Achyranthis Radix with 41 and Euryales Semen with 40. Medicines prescribed more than 30 grams a day included Astragali Radix, Imperatae Rhizoma, Benincasae Pericarpium, Leonuri Herba, Dioscoreae Rhizoma, Plantaginis Semen, Polyporus, Hoelen, Halloysitum Rubrum, Achyranthis Radix, Arecae Pericarpium, Phaseoli Angularis Semen, Coicis Semen, Rhei Rhizoma, Salviae Miltiorrhizae Radix, Sargassum, Ostreae Concha, Pseudostellaria heterophylla, Epimedii Herba, Rehmanniae Radix, Scrophulariae Radix and Polygonati Rhizoma. No scientific reports on the traditional medicinal aspects of diabetic nephropathy was searched. This analysis report would be able to provide the basis of developing new drug candidates for the treatment of diabetic nephropathy, as well as securing the EBM for the traditional medicines already being prescribed to the patients.