CN102988639B - Medicament for treating cervical spondylosis and preparation method of medicament - Google Patents

Abstract

The invention discloses a medicament for treating cervical spondylosis and a preparation method of the medicament. The medicament is mainly prepared from root of red-rooted salvia, caulis spatholobi, pseudo-ginseng, safflower, ligusticum wallichii, radix paeoniae alba, astragalus membranaceus, bighead atractylodes rhizome, cassia twig, ramulus mori, Chinese angelica and the like according to a certain weight proportion. The medicament has functions of relaxing the muscles, stimulating the blood circulation, dredging meridians and collaterals, and strengthening tendon and muscle, and is high in effect taking speed, short in treatment course, and high in curative rate when used for treating the cervical spondylosis without causing reoccurrence.

Description

A kind of medicine for the treatment of cervical spondylosis and preparation method thereof

Technical field

The present invention relates to a kind of medicine for the treatment of cervical spondylosis and preparation method thereof, belong to the field of Chinese medicines.

Background technology

Cervical spondylosis refers to that the plump hypertrophy of degeneration of cervical intervertebral disc, cervical vertebra and neck injury etc. cause hyperosteogeny of cervical vertebra, or prolapse of intervertebral disc, ligament thicken, and stimulates or compressing cervical spinal, cervical region are neural, blood vessel and produce the clinical syndrome of series of symptoms.Main manifestations is the two lower limb spasm of neck and shoulder pain, dizziness headache, upper limb numbness, amyotrophy, severe patient, difficulty in walking, quadriplegia even, and, there is paralysis in defecation obstacle.Multiple at middle-aged and elderly people, male's sickness rate is higher than women.Cervical spondylosis is brought great puzzlement to patient's Working Life, and western medicine cervical spondylosis poor effect, and long-term taking Western medicine at present, has certain side effect, and therefore, people exist great demand to the Chinese medicine of effective treatment cervical spondylosis.

Summary of the invention

The inventor, according to the research of theory of Chinese medical science and clinical test and checking repeatedly, has finally found the medicine of effective treatment cervical spondylosis, thereby has completed the present invention.

Object of the present invention is just to provide a kind of composition of medicine that can treat cervical spondylosis.

Another object of the present invention has just been to provide the preparation method of this composition of medicine.

Medicine of the present invention selects Radix Salviae Miltiorrhizae, Caulis Spatholobi, Radix Notoginseng, Flos Carthami, Rhizoma Chuanxiong, the Radix Paeoniae Alba, the Radix Astragali, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Ramulus Mori, Radix Angelicae Sinensis, Poria, Radix Clematidis, Radix Puerariae, Radix Polygoni Multiflori, Rhizoma Drynariae, Fructus Corni, Radix Rehmanniae Preparata, Rhizoma Typhonii, Herba Cistanches and Cortex Acanthopancis to combine, make each efficacy of drugs produce synergism these drug regimens, thus can fast treating cervical vertebra palindromia.Wherein select Radix Salviae Miltiorrhizae to be because its nature and flavor are bitter, tepor, enters the heart, Liver Channel, has blood circulation and promoting silt, calming heart and tranquilizing mind, evacuation of pus, the function of pain relieving, controls angina cordis, menoxenia, and dysmenorrhea, to close, metrorrhagia leukorrhagia mass in the abdomen, gathers, abdominal pain due to blood stasis, arthralgia, palpitation with fear sleeplessness, malignant boil toxic swelling.Selecting Caulis Spatholobi is because its property bitter but sweet flavor, and temperature, enters the heart, spleen two warps, have invigorate blood circulation, the function of relaxing muscles and tendons, control soreness of waist and knee joint, paralysis and numbness, menoxenia.Selecting Radix Notoginseng is that temperature, enters liver, stomach, large intestine channel, has hemostasis because of its property sweet and slightly bitter taste, dissipating blood stasis, and detumescence, the function of analgesic therapy, controls haematemesis, hemoptysis, epistaxis, has blood in stool, dysentery, metrorrhagia, mass in the abdomen, puerperal blood faints, retention of lochia, falls and flutters blood stasis, traumatic hemorrhage, carbuncle pain.Select Flos Carthami to be because its nature and flavor are pungent, temperature, enters the heart, Liver Channel, has promoting blood circulation to restore menstrual flow, and the function of blood stasis removing pain relieving is controlled amenorrhea ， mass in the abdomen, difficult labour, and stillborn fetus, disease that postpartum lochia can't go, blood stasis is had a pain, carbuncle, injury from falling down.Select Rhizoma Chuanxiong to be because its nature and flavor are pungent, temperature, enters liver, gallbladder meridian, has activating QI to alleviate the depression, dispeiling pathogenic wind and removing dampness, the function of promoting blood circulation and stopping pain, control air-cooled headache revolve dizzy, hypochondriac pain abdomen pain, arthralgia due to cold clonic spasm of the muscle, amenorrhea, difficult labour, postpartum stagnation piece pain, ulcer sores.Select the Radix Paeoniae Alba to be because its nature and flavor picric acid is cool, enter liver, spleen channel, have nourishing blood to suppress the hyperactive liver, slow middle pain relieving, yin fluid astringing is received the function of antiperspirant, controls the breast abdomen pain over the hypochondriac region, dysentery stomachache, spontaneous sweating, fever due to yin deficiency, menoxenia, metrorrhagia, leukorrhagia.Select the Radix Astragali to be because its nature and flavor are sweet, tepor, enters lung, spleen channel, raw with the useful consolidating superficial resistance of defending, inducing diuresis to remove edema, and poison holding, the function of granulation promoting, controls spontaneous perspiration, night sweat, arthralgia due to stagnation of blood, edema, carbuncle is not burst or is burst and hold back for a long time; Process by the function that has invigorating middle warmer benefit, control internal injury overstrain, diarrhea due to hypofunction of the spleen, proctoptosis, deficiency of vital energy blood prostration, the disease of metrorrhagia and leukorrhagia and all weakness of QI blood deficiency.Selecting the Rhizoma Atractylodis Macrocephalae is because its property bitter but sweet flavor, and temperature, enters spleen, stomach warp, has spleen reinforcing, stomach reinforcing, dampness, and in function, control deficient QI of the spleen and stomach, anorexia, asthenia weak breath, deficiency-distension, has loose bowels, phlegm retention, edema, jaundice, arthralgia chiefly caused by damp pathogen, dysuria, dizziness, spontaneous perspiration, nausea is uneasy.Selecting Ramulus Cinnamomi is that temperature, enters bladder, the heart, lung meridian, has diaphoresis expelling pathogenic factors from muscles because of its property acrid-sweet flavor, and the function of warming the meridian and promoting blood circulation, controls exterior syndrome due to wind-cold, shoulder back of the body podomere ache, thoracic obstruction phlegm retention, amenorrhea and mass in the abdomen.Select Ramulus Mori to be because its nature and flavor are bitter, flat, enter Liver Channel, there is wind-damp dispelling, sharp joint, the function of row aqueous vapor, controls anemofrigid-damp arthralgia, spasm of the limbs, beriberi edema, human body pruritus due to wind pathogen.Select Radix Angelicae Sinensis to be because its nature and flavor sweet, acrid, warm enters the heart, liver, spleen channel, have benefiting blood and regulating blood circulation, menstruction regulating and pain relieving, the function of moisturizing laxation, control menoxenia, amenorrhea stomachache ， mass in the abdomen knot is poly-, metrorrhagia, and headache due to deficiency of blood, dizzy, flaccidity syndrome and arthralgia syndrome, dryness of the intestine difficulty just, heavy after bloody dysentery, ulcer sores, incised wound, injury from falling down.Select Poria to be because its property slightly sweet flavor is flat, enter the heart, spleen, lung meridian, have eliminating dampness and diuresis, strengthening the spleen stomach function regulating, the function of mind tranquilizing and the heart calming, controls dysuria edema distending pain, phlegm retention cough with dyspnea, the sound of vomiting of vomitting, has loose bowels, seminal emission, stranguria with turbid discharge, palpitation with fear, forgetful.Select Radix Clematidis to be because its nature and flavor are pungent salty, temperature, poisonous, enter urinary bladder channel, there is wind-damp dispelling, the meridian dredging, expectorant saliva, the function of the loose hypochondriac lump, controls gout, insensitive impediment, chills and pain of the waist and kness, beriberi, malaria ， lumps in the chest and abdomen, tetanus, tonsillitis, all a fishbone or other bone caught in the throat pharynxs.Select Radix Puerariae to be because its nature and flavor are sweet pungent, flat, enter spleen, stomach warp, there is yang invigorating expelling pathogenic factors from muscles, rash antidiarrheal, the function that relieving restlessness is quenched the thirst, cures the wound cold, warm, headache, stiffness of the nape, dysphoria with smothery sensation disappears and drinks, has loose bowels, dysentery, abnormal pigmentary deposit on the skin is examined not saturating, hypertension, angina pectoris, deafness.Select Radix Polygoni Multiflori to be because its property bitter but sweet flavor is puckery, tepor, enters liver, kidney channel, has tonifying liver, and kidney tonifying, nourishes blood, the function of dispeling the wind, control hepatic and renal YIN deficiency, sending out must be early white, and blood deficiency is dizzy, and waist knee joint is weak, and muscles and bones is ached, seminal emission, metrorrhagia and leukorrhagia, chronic malaria, chronic dysentery, chronic hepatitis, carbuncle, scrofula, hemorrhoidal hamorrhage, haemorrhoids.Select Rhizoma Drynariae to be because its nature and flavor are bitter, temperature, enters liver, kidney channel, has the kidney invigorating, invigorates blood circulation, and the function of hemostasis, controls suffer from a deficiency of the kidney chronic diarrhea and lumbago, rheumatic arthralgia, toothache, tinnitus, traumatic injury sprain and contusion, bone injury, appendicitis, alopecia areata, clavus.Select Fructus Corni to be because its nature and flavor are sour, tepor, has invigorating the liver and kidney, and the function of arresting seminal emission gas, controls sexual impotence, seminal emission, and deficiency of the liver cold and heat, the heart shakes scattered pulse.Select Radix Rehmanniae Preparata to be because its nature and flavor are sweet, tepor, enters liver, kidney channel, has YIN nourishing, and the function of enriching blood is controlled deficiency of YIN insufficiency of blood, waist knee flaccidity, and chronic cough hectic fever due to YIN-deficiency, seminal emission, metrorrhagia, menoxenia, quenches one's thirst, frequency of micturition, deafness, blurred vision.Select Rhizoma Typhonii to be because its nature and flavor are pungent, temperature, returns stomach, Liver Channel, the expectorant that dispels the wind, and antispasmodic function, controls apoplexy, facial hemiparalysis, facial paralysis, migraine, tetanus, tuberculous lymphadenitis, carbuncle.Select Herba Cistanches to be because the sweet acid of its nature and flavor is salty, temperature, enters kidney, large intestine channel, has the kidney invigorating, and benefit essence, moisturizes, and the function of bowel relieving, controls impotence in male, infertilitas feminis, leukorrhagia, metrorrhagia, chills and pain of the waist and kness, blood depletion constipation.Select Cortex Acanthopancis to be because its property and flavor of peppery and warm is returned liver, kidney channel, have wind-damp dispelling, strengthening bone and muscle, the function of blood circulation and promoting silt, controls anemofrigid-damp arthralgia, and the sliding contraction of muscle is anxious, edema beriberi, skin ulcer cellulitis toxic swelling, traumatic injury impairment caused by overstrain.

The specific embodiment

The drug dose of component of the present invention is also that inventor draws through groping in a large number to sum up, and the consumption of each component all has good therapeutic effect within the scope of following weight

Radix Salviae Miltiorrhizae 10-20 gram of Caulis Spatholobi 15-25 gram of Radix Notoginseng 8-20 gram

Flos Carthami 10-20 gram of Rhizoma Chuanxiong 15-20 gram of Radix Paeoniae Alba 10-20 gram

Radix Astragali 25-35 gram of Rhizoma Atractylodis Macrocephalae 10-20 gram of Ramulus Cinnamomi 10-20 gram

Ramulus Mori 3-20 gram of Radix Angelicae Sinensis 15-25 gram of Poria 10-20 gram

Radix Clematidis 15-20 gram of Radix Puerariae 10-20 gram of Radix Polygoni Multiflori 8-20 gram

13-20 gram of Radix Rehmanniae Preparata 15-25 gram of Rhizoma Drynariae 10-20 Keshan Fructus Corni

Rhizoma Typhonii 10-20 gram of Herba Cistanches 8-15 gram of Cortex Acanthopancis 8-14 gram

Wherein, be preferably

10 grams of 20 grams of Radix Notoginseng of 15 grams of Caulis Spatholobis of Radix Salviae Miltiorrhizae

12 grams of 18 grams of Radix Paeoniae Albas of 15 grams of Rhizoma Chuanxiongs of Flos Carthami

15 grams of 15 grams of Ramulus Cinnamomi of 30 grams of Rhizoma Atractylodis Macrocephalaes of the Radix Astragali

15 grams, 20 grams of Poria of 15 grams of Radix Angelicae Sinensis of Ramulus Mori

10 grams of 12 grams of Radix Polygoni Multiflori of 18 grams of Radix Puerariaes of Radix Clematidis

18 grams of 16 grams of Radix Rehmanniae Preparata of Rhizoma Drynariae 12 Keshan Fructus Corni

10 grams of 10 grams of Cortex Acanthopanciss of 12 grams of Herba Cistanches of Rhizoma Typhonii

The preparation method of medicine of the present invention is as follows

One, get the raw materials ready

1, Radix Salviae Miltiorrhizae: choose clean impurity, remove rhizome, clean, pull out, run through rear section, dry;

2, Caulis Spatholobi: water runs through, section, or steam after soft and take advantage of fervent sheet, dry;

3, Radix Notoginseng: choose most impurity, smash to pieces, grind or run through section into powder and dry;

4, Flos Carthami: choose clean impurity, remove stem and leaf, base of a fruit head, dry;

5, Rhizoma Chuanxiong: choose decontamination, separate large and small, be soaked in water, solarization is dried in the air, and cuts into slices after moistening, dry;

6, the Radix Paeoniae Alba: choose decontamination, size separately, is soaked in water to eighty per cant saturating, pulls out, and solarization is dried in the air, and profit is even to inside and outside humidity, and section is dry;

7, the Radix Astragali: choose clean impurity, remove residual root head and hollow the greater, be soaked in water, pull out, run through rear timely section, dry;

8, the Rhizoma Atractylodis Macrocephalae: choose clean impurity, be soaked in water, pull out after bubble, run through, section, dries;

9, Ramulus Cinnamomi: water slightly soaks, pulls out, and moistening, to thoroughly, is cut into slices, and dries, and sieves anti-dandruff;

10, Ramulus Mori: choose decontamination, clean, be soaked in water, after running through, cutting, dries;

11, Radix Angelicae Sinensis: choose decontamination, clean, moistening, slightly dries in the air when suitable to inside and outside humidity, and section is dried;

12, Poria: be soaked in water, clean and to pull out, vexed after, cut into slices, dry;

13, Radix Clematidis: choose clean impurity, remove residual stem, be soaked in water, pull out and run through, cutting, dries;

14, Radix Puerariae: choose decontamination, clean, be soaked in water, pull out, run through, section, dries in time;

15, Radix Polygoni Multiflori: choose decontamination, clean, saturating with blister to eighty per cant, to pull out, profit is even to inside and outside humidity, and section or dice, dry;

16, Rhizoma Drynariae: remove sediment contamination, clean, slightly soak, run through, section, dries;

17, Fructus Corni: clean, except removal core and impurity, dry;

18, Radix Rehmanniae Preparata: get crude drug, steam to surperficial corvinus, take out, shines when dry to eighty per cant, section, is dried;

19, Rhizoma Typhonii: remove impurity;

20, Herba Cistanches: choose clean impurity, clear water soaks, changes water every day 1-2 times (as being salty Herba Cistanches, bubble is salinity to the greatest extent), runs through, and section (longitudinally), dries;

21, Cortex Acanthopancis: choose clean impurity, wash, slightly, after profit, section, is dried.

Two, preparation

The Radix Salviae Miltiorrhizae of described weight, Caulis Spatholobi, Radix Notoginseng, Flos Carthami, Rhizoma Chuanxiong, the Radix Paeoniae Alba, the Radix Astragali, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Ramulus Mori, Radix Angelicae Sinensis, Poria, Radix Clematidis, Radix Puerariae, Radix Polygoni Multiflori, Rhizoma Drynariae, Fructus Corni, Radix Rehmanniae Preparata, Rhizoma Typhonii, Herba Cistanches and Cortex Acanthopancis medicine are added to 2000 ml waters, intense fire decocts boiling 30 minutes, use again slow fire boiling 20 minutes, filter and obtain and take medicinal liquid, medicinal liquid is equally divided into 3 doses.

Medicine of the present invention has relaxing muscles and tendons, invigorates blood circulation, and stimulates the menstrual flow, and the function of strengthening bone and muscle, is used for the treatment of cervical spondylosis instant effect, and short treating period, does not recur, and cure rate is high.

By test example, further set forth below the beneficial effect of medicine of the present invention, these tests comprise animal toxicity test and the clinical observation test of medicine of the present invention.

The animal toxicity test report of [test example 1] medicine of the present invention

Get 30 of rabbit, male and female dual-purpose, body weight 2.0-2.5kg, divides two groups, and 15 every group, wherein one group is overdose test group, and another group is normal amount test group.Super quantity group is 30ml/kg, and normal amount is 10ml/kg, and administering mode is administration by gavage administration, once a day, serve on 7 days, observes administration reaction every day, and result shows that two groups of rabbit are movable, diet is normal, and medicine is without bad toxic and side effects.

The clinical observation material of [test example 2] medicine of the present invention

1, physical data:

Accept out-patient's 175 examples for medical treatment.

2, diagnostic criteria:

Cervical spondylosis cardinal symptom is:

(1) neck is takeed on to ache and can be radiated to headrest portion and upper limb;

(2) one sides shoulders back sense of heaviness, upper myasthenia of limbs, points numbly, and limb skin is felt to go down, and holds thing unable, and the automatic thing of holding lands sometimes.

(3) often with head neck shoulder arm, ache, neck has a stiff neck, limitation of activity.

(4) have with dizziness, house rotation, severe one, with nausea and vomiting, is unable to leave the bed, minority can have dizzy, dampings off.

3, Therapeutic Method

Select above-mentioned medicament, each serving with 1 dose, every day, early, middle and late respectively clothes 1 time, 7 days was a course for the treatment of, took continuously 5 courses for the treatment of.

4, efficacy assessment standard

Effective: clinical symptom disappearance after treatment, it is normal that cervical vertebra recovers, and observes half a year without recidivist;

Take a turn for the better: clinical symptoms is obviously improved, and cervical vertebra condition of illness progressively recovers;

Invalid: clinical partial symptoms disappears or without change, do not reach improvement standard person.

5, therapeutic outcome

In above-mentioned treatment, by Drug therapy Patients with Cervical Spondylopathy 175 examples of the present invention, effective 168 examples of result, obvious effective rate is 96%, 4 examples that take a turn for the better, and improvement rate is 2.29%, invalid 3 examples, total effective rate is 98.29%.

Claims (3)

1. a medicine for the treatment of cervical spondylosis, is characterized in that: it is to be made by the crude drug within the scope of following weight:

Radix Salviae Miltiorrhizae 10-20 gram of Caulis Spatholobi 15-25 gram of Radix Notoginseng 8-20 gram

Flos Carthami 10-20 gram of Rhizoma Chuanxiong 15-20 gram of Radix Paeoniae Alba 10-20 gram

Radix Astragali 25-35 gram of Rhizoma Atractylodis Macrocephalae 10-20 gram of Ramulus Cinnamomi 10-20 gram

Ramulus Mori 3-20 gram of Radix Angelicae Sinensis 15-25 gram of Poria 10-20 gram

Radix Clematidis 15-20 gram of Radix Puerariae 10-20 gram of Radix Polygoni Multiflori 8-20 gram

13-20 gram of Radix Rehmanniae Preparata 15-25 gram of Rhizoma Drynariae 10-20 Keshan Fructus Corni

Rhizoma Typhonii 10-20 gram of Herba Cistanches 8-15 gram of Cortex Acanthopancis 8-14 gram.

2. medicine according to claim 1, wherein the consumption of each crude drug is:

10 grams of 20 grams of Radix Notoginseng of 15 grams of Caulis Spatholobis of Radix Salviae Miltiorrhizae

12 grams of 18 grams of Radix Paeoniae Albas of 15 grams of Rhizoma Chuanxiongs of Flos Carthami

15 grams of 15 grams of Ramulus Cinnamomi of 30 grams of Rhizoma Atractylodis Macrocephalaes of the Radix Astragali

15 grams, 20 grams of Poria of 15 grams of Radix Angelicae Sinensis of Ramulus Mori

10 grams of 12 grams of Radix Polygoni Multiflori of 18 grams of Radix Puerariaes of Radix Clematidis

18 grams of 16 grams of Radix Rehmanniae Preparata of Rhizoma Drynariae 12 Keshan Fructus Corni

10 grams of 10 grams of Cortex Acanthopanciss of 12 grams of Herba Cistanches of Rhizoma Typhonii.

3. according to the preparation method of medicine described in claim 1 or 2, it is characterized in that: it comprises the following steps:

(1) get the raw materials ready

(1) Radix Salviae Miltiorrhizae: choose clean impurity, remove rhizome, clean, pull out, run through rear section, dry;

(2) Caulis Spatholobi: water runs through, section, or steam after soft and take advantage of fervent sheet, dry;

(3) Radix Notoginseng: choose most impurity, smash to pieces, grind or run through section into powder and dry;

(4) Flos Carthami: choose clean impurity, remove stem and leaf, base of a fruit head, dry;

(5) Rhizoma Chuanxiong: choose decontamination, separate large and small, be soaked in water, solarization is dried in the air, and cuts into slices after moistening, dry;

(6) Radix Paeoniae Alba: choose decontamination, size separately, is soaked in water to eighty per cant saturating, pulls out, and solarization is dried in the air, and profit is even to inside and outside humidity, and section is dry;

(7) Radix Astragali: choose clean impurity, remove residual root head and hollow the greater, be soaked in water, pull out, run through rear timely section, dry;

(8) Rhizoma Atractylodis Macrocephalae: choose clean impurity, be soaked in water, pull out after bubble, run through, section, dries;

(9) Ramulus Cinnamomi: water slightly soaks, pulls out, and moistening, to thoroughly, is cut into slices, and dries, and sieves anti-dandruff;

(10) Ramulus Mori: choose decontamination, clean, be soaked in water, after running through, cutting, dries;

(11) Radix Angelicae Sinensis: choose decontamination, clean, moistening, slightly dries in the air when suitable to inside and outside humidity, and section is dried;

(12) Poria: be soaked in water, clean and to pull out, vexed after, cut into slices, dry;

(13) Radix Clematidis: choose clean impurity, remove residual stem, be soaked in water, pull out and run through, cutting, dries;

(14) Radix Puerariae: choose decontamination, clean, be soaked in water, pull out, run through, section, dries in time;

(15) Radix Polygoni Multiflori: choose decontamination, clean, saturating with blister to eighty per cant, to pull out, profit is even to inside and outside humidity, and section or dice, dry;

(16) Rhizoma Drynariae: remove sediment contamination, clean, slightly soak, run through, section, dries;

(17) Fructus Corni: clean, except removal core and impurity, dry;

(18) Radix Rehmanniae Preparata: get crude drug, steam to surperficial corvinus, take out, shines when dry to eighty per cant, section, is dried;

(19) Rhizoma Typhonii: remove impurity;

(20) Herba Cistanches: choose clean impurity, clear water soaks, and changes water every day 1-2 times, as is salty Herba Cistanches, and bubble is salinity to the greatest extent, runs through, and longitudinal section, dries;

(21) Cortex Acanthopancis: choose clean impurity, wash, slightly, after profit, section, is dried;

(2) preparation

The Radix Salviae Miltiorrhizae of described weight, Caulis Spatholobi, Radix Notoginseng, Flos Carthami, Rhizoma Chuanxiong, the Radix Paeoniae Alba, the Radix Astragali, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Ramulus Mori, Radix Angelicae Sinensis, Poria, Radix Clematidis, Radix Puerariae, Radix Polygoni Multiflori, Rhizoma Drynariae, Fructus Corni, Radix Rehmanniae Preparata, Rhizoma Typhonii, Herba Cistanches and Cortex Acanthopancis medicine are added to 2000 ml waters, intense fire decocts boiling 30 minutes, use again slow fire boiling 20 minutes, filter and obtain and take medicinal liquid, medicinal liquid is equally divided into 3 doses.